5016 lines
447 KiB
Text
5016 lines
447 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
|
|
|
|
- *600702 - SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 8; SCN8A
|
|
|
|
|
|
- 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=600702"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*600702</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/600702">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=ENSG00000196876;t=ENST00000627620" 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=6334" 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=600702" 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=ENSG00000196876;t=ENST00000627620" 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_001177984,NM_001330260,NM_001369788,NM_014191" 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_001330260" 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=600702" 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=09006&isoform_id=09006_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/SCN8A" 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/4321647,4426571,4958860,6815221,7021531,7657544,9801816,9801818,9801828,18073673,18073675,18073699,21749657,34098756,46369691,46369705,50897535,50897537,50897539,119578601,119578602,119578603,119578604,119578605,119578606,222537873,295789135,1057503272,1621320494" 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/Q9UQD0" 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=6334" 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=ENSG00000196876;t=ENST00000627620" 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=SCN8A" 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=SCN8A" 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+6334" 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/SCN8A" 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:6334" 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/6334" 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=chr12&hgg_gene=ENST00000627620.5&hgg_start=51591233&hgg_end=51812864&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:10596" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:10596" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/scn8a" 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=600702[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=600702[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/SCN8A/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/ENSG00000196876" 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=SCN8A" 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=SCN8A" 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=SCN8A" 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=SCN8A&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/PA35009" 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:10596" 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/FBgn0285944.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:103169" 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/SCN8A#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:103169" 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/6334/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002194/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=6334" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-000828-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=SCN8A&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> 765170001<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>
|
|
600702
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 8; SCN8A
|
|
|
|
</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">
|
|
SODIUM CHANNEL, VOLTAGE-GATED, TYPE VIII, ALPHA SUBUNIT<br />
|
|
NAV1.6
|
|
</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=SCN8A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SCN8A</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/12/390?start=-3&limit=10&highlight=390">12q13.13</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:51591233-51812864&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'})">12:51,591,233-51,812,864</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=618364,614306,614558,617080" 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="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/12/390?start=-3&limit=10&highlight=390">
|
|
12q13.13
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Myoclonus, familial, 2
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618364"> 618364 </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">
|
|
Cognitive impairment with or without cerebellar ataxia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614306"> 614306 </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">
|
|
Developmental and epileptic encephalopathy 13
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614558"> 614558 </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">
|
|
Seizures, benign familial infantile, 5
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617080"> 617080 </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/600702" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/600702" 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>Voltage-dependent sodium channels, such as SCN8A, are responsible for the initial membrane depolarization that occurs during generation of action potentials in most electrically excitable cells (<a href="#19" class="mim-tip-reference" title="Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H. <strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong> Genomics 54: 287-296, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828131</a>] [<a href="https://doi.org/10.1006/geno.1998.5550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9828131">Plummer et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828131" 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="Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H. <strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong> Genomics 54: 287-296, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828131</a>] [<a href="https://doi.org/10.1006/geno.1998.5550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9828131">Plummer et al. (1998)</a> isolated and sequenced genomic fragments containing the exons of a novel human voltage-gated sodium channel designated SCN8A. SCN8A encodes a 1,980-amino acid protein that shares close to 99% sequence identity with the mouse protein. It contains several consensus sites for phosphorylation of serine and threonine residues that are also conserved in other sodium channel family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Plummer, N. W., McBurney, M. W., Meisler, M. H. <strong>Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.</strong> J. Biol. Chem. 272: 24008-24015, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9295353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9295353</a>] [<a href="https://doi.org/10.1074/jbc.272.38.24008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9295353">Plummer et al. (1997)</a> identified 2 alternatively spliced exons of SCN8A, 18N and 18A, that encode transmembrane segments S3 and S4 in domain III. Exon 18N is expressed in fetal brain and nonneuronal tissues. Transcripts with exon 18N have a conserved in-frame stop codon that predicts the synthesis of a truncated, 2-domain protein. The proportion of transcripts containing exon 18N is highest in mouse fetal brain between embryonic day (E) 12.5 and E14.5; at E18.5 and later, the 18A transcript predominates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9295353" 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="#19" class="mim-tip-reference" title="Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H. <strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong> Genomics 54: 287-296, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828131</a>] [<a href="https://doi.org/10.1006/geno.1998.5550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9828131">Plummer et al. (1998)</a> determined that the SCN8A gene contains 28 exons and identified an additional pair of alternatively spliced exons, 5N and 5A, that encode transmembrane segments of domain I. Exons 5N and 5A differ by a single amino acid difference at position 7. <a href="#19" class="mim-tip-reference" title="Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H. <strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong> Genomics 54: 287-296, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828131</a>] [<a href="https://doi.org/10.1006/geno.1998.5550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9828131">Plummer et al. (1998)</a> also found that major and minor protein transcripts are generated by 2 alternative splice donor sites for exon 10B; the minor transcript contains 11 extra amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Drews, V. L., Shi, K., de Haan, G., Meisler, M. H. <strong>Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A.</strong> Mammalian Genome 18: 723-731, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17924165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17924165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17924165[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/10.1007/s00335-007-9059-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17924165">Drews et al. (2007)</a> identified 4 untranslated 5-prime exons, which they designated 1a through 1d, in the mouse and human SCN8A genes. These exons are mutually exclusive, and each is alternatively spliced to the first coding exon. Exon 1a overlaps with an inserted LINE element, and the 70-kb interval between the 5-prime noncoding exons and the first coding exon contains 58% repetitive elements and simple repeats. The Scn8a genes of lower vertebrates contain only a single 5-prime untranslated exon that corresponds to mouse and human exon 1c. Exon 1c contains conserved functional YY1 (<a href="/entry/600013">600013</a>) and REST (<a href="/entry/600571">600571</a>) sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17924165" 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>Active invasion of the dendritic tree by action potentials generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells, this action potential back-propagation is supported by dendritic voltage-gated sodium channels. Using a highly sensitive electron microscopic immunogold technique, <a href="#14" class="mim-tip-reference" title="Lorincz, A., Nusser, Z. <strong>Molecular identify of dendritic voltage-gated sodium channels.</strong> Science 328: 906-909, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20466935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20466935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20466935[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.1187958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20466935">Lorincz and Nusser (2010)</a> revealed the presence of the Nav1.6 subunit in hippocampal CA1 pyramidal cell proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. <a href="#14" class="mim-tip-reference" title="Lorincz, A., Nusser, Z. <strong>Molecular identify of dendritic voltage-gated sodium channels.</strong> Science 328: 906-909, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20466935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20466935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20466935[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.1187958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20466935">Lorincz and Nusser (2010)</a> concluded that their results revealed the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20466935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#11" class="mim-tip-reference" title="Kohrman, D. C., Plummer, N. W., Schuster, T., Jones, J. M., Jang, W., Burgess, D. L., Galt, J., Spear, B. T., Meisler, M. H. <strong>Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.</strong> Genomics 26: 171-177, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7601440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7601440</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80198-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7601440">Kohrman et al. (1995)</a> assigned the mouse Scn8a gene to chromosome 15 by interspecific backcross analysis and the human SCN8A gene to chromosome 12 by hybridization to a somatic cell hybrid mapping panel. <a href="#3" class="mim-tip-reference" title="Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., Meisler, M. H. <strong>Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.</strong> Nature Genet. 10: 461-465, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670495</a>] [<a href="https://doi.org/10.1038/ng0895-461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670495">Burgess et al. (1995)</a> mapped the human homolog to 12q13 by fluorescence in situ hybridization. By physical mapping on a YAC contig, <a href="#19" class="mim-tip-reference" title="Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H. <strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong> Genomics 54: 287-296, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828131</a>] [<a href="https://doi.org/10.1006/geno.1998.5550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9828131">Plummer et al. (1998)</a> localized the SCN8A gene to 12q13.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7601440+7670495+9828131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Cognitive Impairment with or without Cerebellar Ataxia</em></strong></p><p>
|
|
Because SCN8A is widely expressed in neurons of the central and peripheral nervous systems, and because mutations in the mouse ortholog result in ataxia and other movement disorders, <a href="#22" class="mim-tip-reference" title="Trudeau, M. M., Dalton, J. C., Day, J. W., Ranum, L. P. W., Meisler, M. H. <strong>Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. (Letter)</strong> J. Med. Genet. 43: 527-530, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236810</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16236810[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.035667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236810">Trudeau et al. (2006)</a> screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia. They found a 2-bp deletion in exon 24 (<a href="#0001">600702.0001</a>) in a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia (CIAT; <a href="/entry/614306">614306</a>). Three additional family members who were heterozygous for this mutation exhibited milder cognitive behavioral deficits including attention deficit-hyperactivity disorder (ADHD; <a href="/entry/143465">143465</a>). No additional occurrence of this mutation was observed in 625 unrelated DNA samples (1,250 chromosomes). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16236810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated children with CIAT, <a href="#24" class="mim-tip-reference" title="Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., Swinkels, M. E. M., Patel, M. K., Meisler, M. H. <strong>Loss-of-function variants of SCN8A in intellectual disability without seizures.</strong> Neurol. Genet. 3: e170, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28702509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28702509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28702509[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/10.1212/NXG.0000000000000170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28702509">Wagnon et al. (2017)</a> identified de novo heterozygous missense mutations in the SCN8A gene (G964R, <a href="#0013">600702.0013</a> and E1218K, <a href="#0014">600702.0014</a>). The mutations, which were found by exome sequencing, occurred at highly conserved residues in transmembrane domains. In vitro functional expression studies in transfected cells showed that both mutations caused a complete loss of channel activity. <a href="#24" class="mim-tip-reference" title="Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., Swinkels, M. E. M., Patel, M. K., Meisler, M. H. <strong>Loss-of-function variants of SCN8A in intellectual disability without seizures.</strong> Neurol. Genet. 3: e170, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28702509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28702509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28702509[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/10.1212/NXG.0000000000000170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28702509">Wagnon et al. (2017)</a> suggested that loss of neuronal activity due to the mutation may alter the dynamics of synaptic plasticity during maturation and lead to aberrant cerebral circuitry and intellectual disability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28702509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Developmental and Epileptic Encephalopathy 13</em></strong></p><p>
|
|
In a girl with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#23" class="mim-tip-reference" title="Veeramah, K. R., O'Brien, J. E., Meisler, M. H., Cheng, X., Dib-Hajj, S. D., Waxman, S. G., Talwar, D., Girirajan, S., Eichler, E. E., Restifo, L. L., Erickson, R. P., Hammer, M. F. <strong>De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.</strong> Am. J. Hum. Genet. 90: 502-512, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22365152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22365152</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22365152[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.2012.01.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22365152">Veeramah et al. (2012)</a> identified a de novo heterozygous mutation in the SCN8A gene (N1768D; <a href="#0002">600702.0002</a>). In vitro functional expression studies showed that the mutation caused a dominant gain-of-function effect, with neuronal hyperexcitability, persistent sodium currents, incomplete channel inactivation, increased spontaneous firing, paroxysmal-depolarizing-shift-like complexes, and an increased firing frequency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22365152" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others. <strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong> Nature Genet. 45: 825-830, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[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/ng.2646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23708187">Carvill et al. (2013)</a> identified a heterozygous mutation in the SCN8A gene (L1290V; <a href="#0003">600702.0003</a>) in a boy with DEE13. The mutation was inherited from his father, who was found to be somatic mosaic for the mutation. No further clinical information was provided. The patient was part of a cohort of 500 cases of epileptic encephalopathy who underwent sequencing of candidate genes; he was the only patient found to carry an SCN8A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23708187" 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 with DEE13, <a href="#17" class="mim-tip-reference" title="Ohba, C., Kato, M., Takahashi, S., Lerman-Sagie, T., Lev, D., Terashima, H., Kubota, M., Kawawaki, H., Matsufuji, M., Kojima, Y., Tateno, A., Goldberg-Stern, H., and 10 others. <strong>Early onset epileptic encephalopathy caused by de novo SCN8A mutations.</strong> Epilepsia 55: 994-1000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24888894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24888894</a>] [<a href="https://doi.org/10.1111/epi.12668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24888894">Ohba et al. (2014)</a> identified 7 different de novo heterozygous missense mutations in the SCN8A gene (see, e.g., <a href="#0004">600702.0004</a>-<a href="#0006">600702.0006</a>). Whole-exome or targeted capture sequencing detected mutations in 6 (10%) of 60 patients with early-onset epileptic encephalopathy and in 1 (16.7%) of 6 patients diagnosed clinically with malignant migrating partial seizures in infancy (MMPSI). Functional studies of the variants were not performed, but all occurred at highly conserved residues scattered throughout the gene with variable predicted effects. There were no apparent genotype-phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24888894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Benign Familial Infantile Seizures 5</em></strong></p><p>
|
|
In 16 patients from 3 unrelated families with benign familial infantile seizures-5 (BFIS5; <a href="/entry/617080">617080</a>), <a href="#8" class="mim-tip-reference" title="Gardella, E., Becker, F., Moller, R. S., Schubert, J., Lemke, J. R., Larsen, L. H. G., Eiberg, H., Nothnagel, M., Thiele, H., Altmuller, J., Syrbe, S., Merkenschlager, A., and 16 others. <strong>Benign infantile seizure and paroxysmal dyskinesia caused by an SCN8A mutation.</strong> Ann. Neurol. 79: 428-436, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26677014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26677014</a>] [<a href="https://doi.org/10.1002/ana.24580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26677014">Gardella et al. (2016)</a> identified a heterozygous missense mutation in the SCN8A gene (E1483K; <a href="#0010">600702.0010</a>). The variant, which was found by exome sequencing in 2 of the families and confirmed by Sanger sequencing, segregated with the disorder in all 3 families, with evidence of incomplete penetrance. Linkage analysis excluded a founder effect. Although functional studies of the mutation were not performed, <a href="#8" class="mim-tip-reference" title="Gardella, E., Becker, F., Moller, R. S., Schubert, J., Lemke, J. R., Larsen, L. H. G., Eiberg, H., Nothnagel, M., Thiele, H., Altmuller, J., Syrbe, S., Merkenschlager, A., and 16 others. <strong>Benign infantile seizure and paroxysmal dyskinesia caused by an SCN8A mutation.</strong> Ann. Neurol. 79: 428-436, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26677014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26677014</a>] [<a href="https://doi.org/10.1002/ana.24580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26677014">Gardella et al. (2016)</a> postulated that it caused a small gain-of-function effect resulting from impaired channel inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26677014" 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 father and son with BFIS5, <a href="#1" class="mim-tip-reference" title="Anand, G., Collett-White, F., Orsini, A., Thomas, S., Jayapal, S., Trump, N., Zaiwalla, Z., Jayawant, S. <strong>Autosomal dominant SCN8A mutation with an unusually mild phenotype.</strong> Europ. J. Paediat. Neurol. 20: 761-765, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27210545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27210545</a>] [<a href="https://doi.org/10.1016/j.ejpn.2016.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27210545">Anand et al. (2016)</a> identified a heterozygous missense mutation in the SCN8A gene (N1877S; <a href="#0011">600702.0011</a>). Functional studies of the variant were not performed, but <a href="#1" class="mim-tip-reference" title="Anand, G., Collett-White, F., Orsini, A., Thomas, S., Jayapal, S., Trump, N., Zaiwalla, Z., Jayawant, S. <strong>Autosomal dominant SCN8A mutation with an unusually mild phenotype.</strong> Europ. J. Paediat. Neurol. 20: 761-765, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27210545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27210545</a>] [<a href="https://doi.org/10.1016/j.ejpn.2016.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27210545">Anand et al. (2016)</a> noted that the same variant has been identified in patients with a more severe disorder, including developmental delay, epileptic encephalopathy, and intellectual disability (DEE13). The benign phenotype in the father and son suggested that they may carry additional variants in other genes that offer a protective effect. Sanger sequencing excluded somatic mosaicism for the SCN8A mutation in the father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27210545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Familial Myoclonic Epilepsy 2</em></strong></p><p>
|
|
In 3 affected members of a family with myoclonic epilepsy-2 (MYOCL2; <a href="/entry/618364">618364</a>), <a href="#25" class="mim-tip-reference" title="Wagnon, J. L., Mencacci, N. E., Barker, B. S., Wengert, E. R., Bhatia, K. P., Balint, B., Carecchio, M., Wood, N. W., Patel, M. K., Meisler, M. H. <strong>Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus.</strong> Hum. Mutat. 39: 965-969, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29726066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29726066</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29726066[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.23547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29726066">Wagnon et al. (2018)</a> identified a heterozygous missense mutation in the SCN8A gene (P1719R; <a href="#0012">600702.0012</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family in those who agreed to testing. In vitro functional expression studies in transfected neuron-derived cells showed that the mutation caused a partial loss of function, manifest as decreased inward sodium current compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29726066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with developmental delay, impaired intellectual development, and early-onset seizures, <a href="#2" class="mim-tip-reference" title="Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J. <strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong> J. Med. Genet. 52: 330-337, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25725044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25725044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25725044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25725044">Blanchard et al. (2015)</a> identified 2 different de novo heterozygous missense mutations in the SCN8A gene (N984K, <a href="#0008">600702.0008</a> and G1451S, <a href="#0009">600702.0009</a>). The patients were ascertained from a cohort of 500 patients with intellectual disability and 100 patients with a movement disorder who underwent exome sequencing. In vitro functional expression studies showed that the N984K mutation resulted in increased channel opening and increased neuronal excitability, consistent with a gain of function, whereas the G1451S mutation resulted in decreased current density, consistent with a loss of function. The patient with the N984K mutation had onset of intractable seizures at age 6 weeks and severe developmental delay with no speech and inability to sit independently at age 7 years; the patient with the G1451S mutation had a slightly less severe phenotype, with onset of seizures at age 18 months, moderate to severe developmental delay, spastic tetraplegia, ataxia, and nystagmus with cerebellar atrophy at age 33 years. <a href="#2" class="mim-tip-reference" title="Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J. <strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong> J. Med. Genet. 52: 330-337, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25725044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25725044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25725044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25725044">Blanchard et al. (2015)</a> concluded that SCN8A mutations resulting in a gain of function may result in a more severe phenotype, but noted that the G1451S mutation may also have some gain-of-function effects that were not detected in the cellular assay. A third unrelated patient with severe developmental delay (IQ of 55), dysmorphic features, and no seizures had a heterozygous D58N variant in the SCN8A gene, but functional studies showed normal SCN8A channel activity, suggesting that the variant may not be pathogenic. This patient also carried a heterozygous R95Q variant in the RING1 gene (<a href="/entry/602045">602045</a>), but functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25725044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The mouse neurologic mutant 'motor endplate disease' (med) is characterized by early-onset progressive paralysis of the hindlimbs, severe muscle atrophy, degeneration of Purkinje cells, and juvenile lethality. <a href="#3" class="mim-tip-reference" title="Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., Meisler, M. H. <strong>Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.</strong> Nature Genet. 10: 461-465, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670495</a>] [<a href="https://doi.org/10.1038/ng0895-461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670495">Burgess et al. (1995)</a> isolated a voltage-gated sodium channel gene, Scn8a, from the flanking region of a transgene-induced allele of med. Scn8a is expressed in brain and spinal cord but not in skeletal muscle or heart, and encodes a predicted protein of 1,732 amino acids. An intragenic deletion at the site of transgene insertion resulted in loss of expression. The gene is closely related to other sodium channel alpha subunits: SCN1A (<a href="/entry/182389">182389</a>), SCN2A (<a href="/entry/182390">182390</a>), SCN3A (<a href="/entry/182391">182391</a>), SCN4A (<a href="/entry/603967">603967</a>), SCN5A (<a href="/entry/600163">600163</a>), and SCN6A (<a href="/entry/182392">182392</a>). <a href="#12" class="mim-tip-reference" title="Kohrman, D. C., Smith, M. R., Goldin, A. L., Harris, J., Meisler, M. H. <strong>A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting.</strong> J. Neurosci. 16: 5993-5999, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8815882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8815882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8815882[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/10.1523/JNEUROSCI.16-19-05993.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8815882">Kohrman et al. (1996)</a> identified a missense mutation in Scn8a that is associated with cerebellar ataxia in the 'jolting' mutant, a mild allele of the med locus. <a href="#10" class="mim-tip-reference" title="Kohrman, D. C., Harris, J. B., Meisler, M. H. <strong>Mutation detection in the med and med(J) alleles of the sodium channel Scn8a: unusual splicing due to a minor class AT-AC intron.</strong> J. Biol. Chem. 271: 17576-17581, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663325</a>] [<a href="https://doi.org/10.1074/jbc.271.29.17576" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663325">Kohrman et al. (1996)</a> described the molecular changes in Scn8a underlying 2 other spontaneous mutants, med and med(J). The med mutation was caused by insertion of a truncated LINE element into exon 2 of Scn8a. The med transcript was spliced from exon 1 to a cryptic acceptor site in intron 2. In the med(J) allele, a 4-bp deletion within 5-prime donor site of exon 3 resulted in splicing from exon 1 to exon 4. Both mutant transcripts altered the reading frame with premature stop codons close to the N terminus of the protein. Loss of Scn8a expression resulted in progressive paralysis and early death. Intron 2 of Scn8a is flanked by minor class AT-AC splice sites. The observed splicing patterns of the med and med(J) mutant transcripts provided evidence for preferential in vivo splicing between donor and acceptor sites of the same class. The apparent functional incompatibility may be a consequence of the different composition of spliceosomes bound to major and minor splice sites. The unusual pattern of exon skipping in these mutant identified Scn8a as a member of a small group of genes containing introns with nonstandard AT-AC splice sites. AT-AC introns are processed by alternative splicing machinery that includes U11 and U12 (RNU12; <a href="/entry/620204">620204</a>) snRNPs. <a href="#16" class="mim-tip-reference" title="Meisler, M. H., Sprunger, L. K., Plummer, N. W., Escayg, A., Jones, J. M. <strong>Ion channel mutations in mouse models of inherited neurological disease.</strong> Ann. Med. 29: 569-574, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9562526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9562526</a>] [<a href="https://doi.org/10.3109/07853899709007484" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9562526">Meisler et al. (1997)</a> reviewed how the analysis of molecular defects in mouse mutants can identify candidate genes for human neurologic disorders, as illustrated by Scn8a among other genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7670495+8815882+9562526+8663325" 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="Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H. <strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong> Hum. Molec. Genet. 8: 471-479, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949206</a>] [<a href="https://doi.org/10.1093/hmg/8.3.471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9949206">Sprunger et al. (1999)</a> studied the mouse mutant med(J), which contains a splice site mutation in the neuronal sodium channel Scn8a that results in a very low level of expression. On the C57BL/6J genetic background, med(J) homozygotes exhibited progressive paralysis and juvenile lethality. The C3H genetic background had an ameliorating effect, producing viable adults with a novel dystonic phenotype. The dystonic mice exhibited movement-induced, sustained abnormal postures of the trunk and limbs. <a href="#21" class="mim-tip-reference" title="Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H. <strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong> Hum. Molec. Genet. 8: 471-479, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949206</a>] [<a href="https://doi.org/10.1093/hmg/8.3.471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9949206">Sprunger et al. (1999)</a> mapped a dominant modifier locus responsible for the difference between strains to a 4.5 +/- 1.3-cM interval on mouse chromosome 3. These findings established a role for ion channels in dystonia and demonstrated the impact of genetic background on its severity and progression. This new model suggested to <a href="#21" class="mim-tip-reference" title="Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H. <strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong> Hum. Molec. Genet. 8: 471-479, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949206</a>] [<a href="https://doi.org/10.1093/hmg/8.3.471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9949206">Sprunger et al. (1999)</a> that SCN8A on 12q13 and SCNM1 (which by comparative mapping is presumably located on 1p21-q21) may contribute to human inherited dystonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9949206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The dystonia demonstrated by <a href="#21" class="mim-tip-reference" title="Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H. <strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong> Hum. Molec. Genet. 8: 471-479, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949206</a>] [<a href="https://doi.org/10.1093/hmg/8.3.471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9949206">Sprunger et al. (1999)</a> in association with the Scn8a mutation was the first to be related to mutation in an ion channel. Furthermore, the med(J) mouse differed from other animal models with dystonia in that the condition persisted to adulthood and was not associated with neurodegeneration. <a href="#21" class="mim-tip-reference" title="Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H. <strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong> Hum. Molec. Genet. 8: 471-479, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949206</a>] [<a href="https://doi.org/10.1093/hmg/8.3.471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9949206">Sprunger et al. (1999)</a> suggested that the med(J) mutation should be classified as a hypomorphic allele because a low level of full-length Scn8a transcripts was demonstrated in homozygotes, indicating normal splicing at low efficiency. Homozygotes for null alleles of Scn8a could not survive even in the presence of 2 copies of the Scnm1(H) modifier allele. Thus, prevention of paralysis and survival to adulthood required both a low level of wildtype transcript and at least 1 copy of the dominant allele of Scnm1. C57BL/6J carries a recessive allele of Scmn1 that, in combination with a hypomorphic level of Scn8a, resulted in paralysis and lethality. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9949206" 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="De Repentigny, Y., Cote, P. D., Pool, M., Bernier, G., Girard, S., Vidal, S. M., Kothary, R. <strong>Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new allele of Scn8a.</strong> Hum. Molec. Genet. 10: 1819-1827, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11532991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11532991</a>] [<a href="https://doi.org/10.1093/hmg/10.17.1819" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11532991">De Repentigny et al. (2001)</a> described a spontaneous autosomal recessive mutation in the mouse, which they termed 'degenerating muscle' (dmu), that is characterized by skeletal and cardiac muscle degeneration. Dmu mice are weak and have great difficulty in moving due to muscle atrophy and wasting in the hindquarters. Histopathologic observations and ultrastructural analysis revealed muscle degeneration in both skeletal and cardiac muscle, but no abnormalities in sciatic nerves. Using linkage analysis, the authors mapped the dmu locus to the distal portion of mouse chromosome 15 in a region syntenic to human chromosome 12q13. Intact transcripts for Scn8a were present in dmu mice, but their levels were dramatically reduced. Furthermore, genetic complementation crosses between dmu and med mice revealed that they are allelic. The authors concluded that at least a portion of the dmu phenotype may be caused by a downregulation of Scn8a. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11532991" 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="#9" class="mim-tip-reference" title="Kearney, J. A., Buchner, D. A., de Haan, G., Adamska, M., Levin, S. I., Furay, A. R., Albin, R. L., Jones, J. M., Montal, M., Stevens, M. J., Sprunger, L. K., Meisler, M. H. <strong>Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Nav1.6).</strong> Hum. Molec. Genet. 11: 2765-2775, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374766</a>] [<a href="https://doi.org/10.1093/hmg/11.22.2765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12374766">Kearney et al. (2002)</a> described a sensitive allele of the unlinked modifier locus, Scnm1, which results in juvenile lethality in C57BL/6J mice carrying the med(J) mutation. The modifier acts on the splicing efficiency of the mutant splice donor site in Scn8a, and mutant mice display either 90% or 95% reduction in the proportion of correctly spliced mRNA, depending on modifier genotype. The abundance of the channel protein, NaV1.6, is also reduced by an order of magnitude in med(J) mice, resulting in delayed maturation of nodes of Ranvier, slowed nerve conduction velocity, reduced muscle mass, and reduction of brain metabolic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374766" 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="Martin, M. S., Tang, B., Papale, L. A., Yu, F. H., Catterall, W. A., Escayg, A. <strong>The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy.</strong> Hum. Molec. Genet. 16: 2892-2899, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881658</a>] [<a href="https://doi.org/10.1093/hmg/ddm248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881658">Martin et al. (2007)</a> showed that Scn8a(med) and Scn8a(med-jo) mice, which carry the heterozygous 'jolting' point mutation, were more resistant to pharmacologically induced seizures than wildtype littermates, suggesting that altered Scn8a function reduces neuronal excitability. They also showed that the seizure severity of heterozygous Scn1a +/- mice (see <a href="#26" class="mim-tip-reference" title="Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., Spain, W. J., McKnight, G. S., Scheuer, T., Catterall, W. A. <strong>Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.</strong> Nature Neurosci. 9: 1142-1149, 2006. Note: Erratum: Nature Neurosci. 10: 134 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16921370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16921370</a>] [<a href="https://doi.org/10.1038/nn1754" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16921370">Yu et al., 2006</a>), which is a mouse model for severe myoclonic epilepsy of infancy (SMEI; <a href="/entry/607208">607208</a>), was ameliorated by the Scn8a(med-jo) allele. Double-heterozygous Scn1a +/- and Scn8a +/(med-jo) mice had seizure thresholds that were comparable to wildtype littermates, and the Scn8a(med-jo) allele was also able to rescue the premature lethality of Scn1a +/- mice and extended the life span of Scn1a -/- mice. The authors hypothesized that the opposing effects of Scn1a and Scn8a dysfunction on seizure thresholds result from differences in the cell types that are influenced by the respective sodium channel subtypes. Scn1a mutants result in reduced sodium currents in inhibitory GABAergic interneurons of the hippocampus and cortex, whereas Scn8a mutants affect excitatory pyramidal cells of the hippocampus and cortex, suggesting that reduced excitability of these cells may underlie the elevated seizure resistance of Scn8a-mutant mice. <a href="#15" class="mim-tip-reference" title="Martin, M. S., Tang, B., Papale, L. A., Yu, F. H., Catterall, W. A., Escayg, A. <strong>The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy.</strong> Hum. Molec. Genet. 16: 2892-2899, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881658</a>] [<a href="https://doi.org/10.1093/hmg/ddm248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881658">Martin et al. (2007)</a> suggested that their results demonstrated that genetic interactions can alter seizure severity, and supported the hypothesis that genetic modifiers, including the SCN8A gene, contribute to the clinical variability observed in SMEI and GEFS+. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16921370+17881658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By ENU-induced mutagenesis screen in mice, <a href="#18" class="mim-tip-reference" title="Papale, L. A., Beyer, B., Jones, J. M., Sharkey, L. M., Tufik, S., Epstein, M., Letts, V. A., Meisler, M. H., Frankel, W. N., Escayg, A. <strong>Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice.</strong> Hum. Molec. Genet. 18: 1633-1641, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19254928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19254928</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19254928[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19254928">Papale et al. (2009)</a> generated a val929-to-phe (V929F) mutation in the Scn8a gene. This residue in the pore loop of domain 2 is evolutionarily conserved. Electroencephalography (EEG) revealed well-defined spike-wave discharges (SWD), the hallmark of absence epilepsy (see <a href="/entry/600131">600131</a>), in V929F-heterozygous mice and in mice heterozygous for either the Scn8a(med) or Scn8a(med-jo) mutations. Genetic background had a significant effect on SWD, with mutants on the C3HeB/FeJ strain showing a higher incidence than on C57BL/6J. <a href="#18" class="mim-tip-reference" title="Papale, L. A., Beyer, B., Jones, J. M., Sharkey, L. M., Tufik, S., Epstein, M., Letts, V. A., Meisler, M. H., Frankel, W. N., Escayg, A. <strong>Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice.</strong> Hum. Molec. Genet. 18: 1633-1641, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19254928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19254928</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19254928[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19254928">Papale et al. (2009)</a> suggested that the SCN8A gene may be a candidate gene for absence epilepsy in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19254928" 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="Letko, A., Dietschi, E., Nieburg, M., Jagannathan, V., Gurtner, C., Oevermann, A., Drogemuller, C. <strong>A missense variant in SCN8A in Alpine Dachsbracke dogs affected by spinocerebellar ataxia.</strong> Genes (Basel) 10: 362, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31083464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31083464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31083464[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/10.3390/genes10050362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31083464">Letko et al. (2019)</a> identified a homozygous missense variant (gly1633 to val, G1633V) in the SCN8A gene in 4 Alpine Dachsbracke dogs affected with spinocerebellar ataxia characterized by ataxia, tremor, loss of balance and axonal degeneration. Pathogenicity of the mutation was supported by genotyping studies in over 200 dogs of this breed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31083464" 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>14 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/600702" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600702[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 COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, 2-BP DEL, 5156CT
|
|
</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> rs587776703 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776703;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/rs587776703?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=rs587776703" 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=rs587776703" 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=RCV000009467 OR RCV004589503" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009467, RCV004589503" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009467...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia (CIAT; <a href="/entry/614306">614306</a>), <a href="#22" class="mim-tip-reference" title="Trudeau, M. M., Dalton, J. C., Day, J. W., Ranum, L. P. W., Meisler, M. H. <strong>Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. (Letter)</strong> J. Med. Genet. 43: 527-530, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236810</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16236810[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.035667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236810">Trudeau et al. (2006)</a> identified heterozygosity for a 2-bp deletion in exon 24 of the SCN8A gene, which introduced a translation termination codon into the pore loop of domain 4, resulting in removal of the C-terminal cytoplasmic domain and predicting loss of channel function (Pro1719ArgfsTer6). The authors stated in the text that the deletion removed nucleotides 5156 and 5157, and in Figure 1 that it removed nucleotides 5157 and 5158. Three additional heterozygous family members exhibited milder cognitive and behavioral deficits including attention deficit-hyperactivity disorder (ADHD; <a href="/entry/143465">143465</a>). <a href="#22" class="mim-tip-reference" title="Trudeau, M. M., Dalton, J. C., Day, J. W., Ranum, L. P. W., Meisler, M. H. <strong>Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. (Letter)</strong> J. Med. Genet. 43: 527-530, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236810</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16236810[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.035667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236810">Trudeau et al. (2006)</a> noted that it was unclear whether the relatives of the proband had a milder version of the neurologic abnormalities seen in the proband due to haploinsufficiency for SCN8A, or if the proband's symptoms were caused by an unrelated developmental disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16236810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ASN1768ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs202151337 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202151337;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=rs202151337" 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=rs202151337" 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=RCV000023031 OR RCV001230237 OR RCV003992161" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023031, RCV001230237, RCV003992161" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023031...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#23" class="mim-tip-reference" title="Veeramah, K. R., O'Brien, J. E., Meisler, M. H., Cheng, X., Dib-Hajj, S. D., Waxman, S. G., Talwar, D., Girirajan, S., Eichler, E. E., Restifo, L. L., Erickson, R. P., Hammer, M. F. <strong>De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.</strong> Am. J. Hum. Genet. 90: 502-512, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22365152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22365152</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22365152[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.2012.01.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22365152">Veeramah et al. (2012)</a> identified a de novo heterozygous c.5302A-G transition (c.5302A-G, NM_014191.2) in the SCN8A gene, resulting in an asn1768-to-asp (N1768D) substitution in a highly conserved residue in the final transmembrane segment adjacent to the C-terminal cytoplasmic domain. The mutation was identified by whole-genome sequencing. Expression of the mutant protein in a neuronal cell line showed that it caused persistent sodium currents, incomplete channel inactivation, and a depolarizing shift in the voltage dependence of steady-state fast inactivation. Current-clamp analysis in rat hippocampal neurons transfected with the mutant protein showed increased spontaneous firing, paroxysmal-depolarizing-shift-like complexes, and an increased firing frequency, consistent with a dominant gain-of-function phenotype. All of these studies were consistent with neuronal hyperexcitability. Whole-genome sequencing also identified putative recessive variants in the NRP2 (<a href="/entry/602070">602070</a>) and UNC13C (<a href="/entry/614568">614568</a>) genes in the proband, which may have contributed to the phenotype. The patient developed refractory generalized seizures at age 6 months. At age 4 years, the seizure phenotype changed to epileptic spasms, followed by regression of speech and language skills. She also had developmental delay, intellectual disability, autism, hypotonia, and difficulties with coordination and balance. Initial electroencephalogram (EEG) showed bifrontal spikes and brief bursts of generalized spike-wave activity. Later EEG showed diffuse slowing, multifocal spikes, and frontally predominant generalized spikes. Brain MRI was normal. The patient died suddenly at age 15 years. There was no family history of a similar disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22365152" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, LEU1290VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514738 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514738;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=rs397514738" 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=rs397514738" 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=RCV000054506 OR RCV003992171" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054506, RCV003992171" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054506...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy (patient T2939) with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#4" class="mim-tip-reference" title="Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others. <strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong> Nature Genet. 45: 825-830, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[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/ng.2646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23708187">Carvill et al. (2013)</a> identified a heterozygous c.3868C-G transversion (c.3868C-G, NM_001177984.2) in the SCN8A gene, resulting in a leu1290-to-val (L1290V) substitution. The patient had onset of seizures at age 18 months. The mutation was inherited from the father, who was found to be somatic mosaic for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23708187" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ARG1617GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777721 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777721;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=rs587777721" 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=rs587777721" 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=RCV000144154 OR RCV000522954 OR RCV000636307 OR RCV000678845 OR RCV001266283 OR RCV003992195" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144154, RCV000522954, RCV000636307, RCV000678845, RCV001266283, RCV003992195" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144154...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old Japanese girl (patient 4) with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#17" class="mim-tip-reference" title="Ohba, C., Kato, M., Takahashi, S., Lerman-Sagie, T., Lev, D., Terashima, H., Kubota, M., Kawawaki, H., Matsufuji, M., Kojima, Y., Tateno, A., Goldberg-Stern, H., and 10 others. <strong>Early onset epileptic encephalopathy caused by de novo SCN8A mutations.</strong> Epilepsia 55: 994-1000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24888894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24888894</a>] [<a href="https://doi.org/10.1111/epi.12668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24888894">Ohba et al. (2014)</a> identified a de novo heterozygous c.4850G-A transition (c.4850G-A, NM_014191.3) in the SCN8A gene, resulting in an arg1617-to-gln (R1617Q) substitution at a highly conserved residue in the S4 transmembrane segment that plays a role in voltage sensing. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of seizures at 3 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24888894" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ASN1466LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777722 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777722;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=rs587777722" 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=rs587777722" 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=RCV000144155" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144155" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144155</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Japanese boy (patient 1) with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#17" class="mim-tip-reference" title="Ohba, C., Kato, M., Takahashi, S., Lerman-Sagie, T., Lev, D., Terashima, H., Kubota, M., Kawawaki, H., Matsufuji, M., Kojima, Y., Tateno, A., Goldberg-Stern, H., and 10 others. <strong>Early onset epileptic encephalopathy caused by de novo SCN8A mutations.</strong> Epilepsia 55: 994-1000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24888894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24888894</a>] [<a href="https://doi.org/10.1111/epi.12668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24888894">Ohba et al. (2014)</a> identified a de novo heterozygous c.4398C-A transversion (c.4398C-A, NM_014191.3) in the SCN8A gene, resulting in an asn1466-to-lys (N1466K) substitution at a highly conserved residue in the linker region between domains III and IV that forms an inactivation gate. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of intractable seizures on day 3 of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24888894" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ASN1466THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777723 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777723;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=rs587777723" 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=rs587777723" 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=RCV000144156" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144156" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144156</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Israeli boy (patient 5) with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#17" class="mim-tip-reference" title="Ohba, C., Kato, M., Takahashi, S., Lerman-Sagie, T., Lev, D., Terashima, H., Kubota, M., Kawawaki, H., Matsufuji, M., Kojima, Y., Tateno, A., Goldberg-Stern, H., and 10 others. <strong>Early onset epileptic encephalopathy caused by de novo SCN8A mutations.</strong> Epilepsia 55: 994-1000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24888894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24888894</a>] [<a href="https://doi.org/10.1111/epi.12668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24888894">Ohba et al. (2014)</a> identified a de novo heterozygous c.4397A-C transversion (c.4397A-C, NM_014191.3) in the SCN8A gene, resulting in an asn1466-to-thr (N1466T) substitution at a highly conserved residue in the linker region between domains III and IV that forms an inactivation gate. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of seizures at 4 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24888894" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ARG223GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs672601319 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs672601319;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=rs672601319" 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=rs672601319" 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=RCV000149436" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149436" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149436</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old girl with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#5" class="mim-tip-reference" title="de Kovel, C. G. F., Meisler, M. H., Brilstra, E. H., van Berkestijn, F. M. C., van't Slot, R., van Lieshout, S., Nijman, I. J., O'Brien, J. E., Hammer, M. F., Estacion, M., Waxman, S. G., Dib-Hajj, S. D., Koeleman, B. P. C. <strong>Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.</strong> Epilepsy Res. 108: 1511-1518, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25239001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25239001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25239001[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.eplepsyres.2014.08.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25239001">de Kovel et al. (2014)</a> identified a de novo heterozygous c.667A-G transition in the SCN8A gene, resulting in an arg223-to-gly (R223G) substitution at a highly conserved residue in the voltage-sensing transmembrane segment 4 of domain 1 (D1S4). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. In vitro cellular functional expression studies showed that the mutant protein had significantly reduced stability (about 20% of wildtype) and that the mutant channel had reduced peak current amplitude (20% of wildtype) at 37 degrees C. There was a 3-fold increase in the ramp current at 30 degrees C, but this was still a significant reduction in terms of absolute current levels. The findings were consistent with a loss-of-function effect. <a href="#5" class="mim-tip-reference" title="de Kovel, C. G. F., Meisler, M. H., Brilstra, E. H., van Berkestijn, F. M. C., van't Slot, R., van Lieshout, S., Nijman, I. J., O'Brien, J. E., Hammer, M. F., Estacion, M., Waxman, S. G., Dib-Hajj, S. D., Koeleman, B. P. C. <strong>Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.</strong> Epilepsy Res. 108: 1511-1518, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25239001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25239001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25239001[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.eplepsyres.2014.08.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25239001">De Kovel et al. (2014)</a> noted that SCN8A is expressed in inhibitory neurons, where a loss of function may yield an epileptic phenotype. The patient had onset of seizures at 6 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25239001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ASN984LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs876657399 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876657399;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=rs876657399" 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=rs876657399" 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=RCV000172909 OR RCV001003602 OR RCV003992211" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172909, RCV001003602, RCV003992211" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172909...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old girl with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#2" class="mim-tip-reference" title="Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J. <strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong> J. Med. Genet. 52: 330-337, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25725044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25725044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25725044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25725044">Blanchard et al. (2015)</a> identified a de novo heterozygous c.2952C-G transversion (c.2952C-G, NM_014191.2) in the SCN8A gene, resulting in an asn984-to-lys (N984K) substitution at a highly conserved residue adjacent to the transmembrane segment of the channel. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies in HEK293 cells showed that the mutation caused a 10-mV hyperpolarization shift, predicting premature channel opening and neuronal hyperactivity. The findings were consistent with a gain of function. The patient had onset of intractable seizures at 6 weeks of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25725044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, GLY1451SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs863223345 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863223345;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=rs863223345" 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=rs863223345" 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=RCV000172910 OR RCV000517164 OR RCV001380064 OR RCV002516572 OR RCV003320591 OR RCV003992212" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172910, RCV000517164, RCV001380064, RCV002516572, RCV003320591, RCV003992212" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172910...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 33-year-old man with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>), <a href="#2" class="mim-tip-reference" title="Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J. <strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong> J. Med. Genet. 52: 330-337, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25725044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25725044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25725044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25725044">Blanchard et al. (2015)</a> identified a de novo heterozygous c.4351G-A transition (c.4351G-A, NM_014191.2) in the SCN8A gene, resulting in a gly1451-to-ser (G1451S) substitution at a conserved residue in transmembrane segment D3S6. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies in HEK293 cells showed that the mutation caused a 10-fold decrease in current density compared to wildtype, consistent with a loss of function. However, <a href="#2" class="mim-tip-reference" title="Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J. <strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong> J. Med. Genet. 52: 330-337, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25725044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25725044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25725044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25725044">Blanchard et al. (2015)</a> postulated that the mutant protein may also have a dominant effect. The patient had onset of seizures at 18 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25725044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SEIZURES, BENIGN FAMILIAL INFANTILE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, GLU1483LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs879255652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs879255652;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=rs879255652" 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=rs879255652" 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=RCV000239671 OR RCV001293365 OR RCV001556220 OR RCV002226427 OR RCV002518547 OR RCV003992245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239671, RCV001293365, RCV001556220, RCV002226427, RCV002518547, RCV003992245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239671...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 16 patients from 3 unrelated families with benign familial infantile seizures-5 (BFIS5; <a href="/entry/617080">617080</a>), <a href="#8" class="mim-tip-reference" title="Gardella, E., Becker, F., Moller, R. S., Schubert, J., Lemke, J. R., Larsen, L. H. G., Eiberg, H., Nothnagel, M., Thiele, H., Altmuller, J., Syrbe, S., Merkenschlager, A., and 16 others. <strong>Benign infantile seizure and paroxysmal dyskinesia caused by an SCN8A mutation.</strong> Ann. Neurol. 79: 428-436, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26677014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26677014</a>] [<a href="https://doi.org/10.1002/ana.24580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26677014">Gardella et al. (2016)</a> identified a heterozygous c.4447G-A transition in the SCN8A gene, resulting in a glu1483-to-lys (E1483K) substitution at a highly conserved residue in the intracellular loop between domains III and IV. The variant, which was found by exome sequencing in 2 of the families and confirmed by Sanger sequencing, segregated with the disorder in all 3 families, with evidence of incomplete penetrance. The mutation was not found in the dbSNP (build 138), 1000 Genomes Project, Exome Variant Server, or ExAC databases. Linkage analysis excluded a founder effect. Although functional studies of the mutation were not performed, <a href="#8" class="mim-tip-reference" title="Gardella, E., Becker, F., Moller, R. S., Schubert, J., Lemke, J. R., Larsen, L. H. G., Eiberg, H., Nothnagel, M., Thiele, H., Altmuller, J., Syrbe, S., Merkenschlager, A., and 16 others. <strong>Benign infantile seizure and paroxysmal dyskinesia caused by an SCN8A mutation.</strong> Ann. Neurol. 79: 428-436, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26677014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26677014</a>] [<a href="https://doi.org/10.1002/ana.24580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26677014">Gardella et al. (2016)</a> postulated that it caused a small gain-of-function effect resulting from impaired channel inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26677014" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SEIZURES, BENIGN FAMILIAL INFANTILE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, ASN1877SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587780455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587780455;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=rs587780455" 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=rs587780455" 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=RCV000118288 OR RCV000239630 OR RCV000239702 OR RCV000416967 OR RCV000467598 OR RCV002274920 OR RCV003992186" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000118288, RCV000239630, RCV000239702, RCV000416967, RCV000467598, RCV002274920, RCV003992186" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000118288...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and son with benign familial infantile seizures-5 (BFIS5; <a href="/entry/617080">617080</a>), <a href="#1" class="mim-tip-reference" title="Anand, G., Collett-White, F., Orsini, A., Thomas, S., Jayapal, S., Trump, N., Zaiwalla, Z., Jayawant, S. <strong>Autosomal dominant SCN8A mutation with an unusually mild phenotype.</strong> Europ. J. Paediat. Neurol. 20: 761-765, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27210545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27210545</a>] [<a href="https://doi.org/10.1016/j.ejpn.2016.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27210545">Anand et al. (2016)</a> identified a heterozygous c.5630A-G transition (c.5630A-G, NM_014191.3) in the SCN8A gene, resulting in an asn1877-to-ser (N1877S) substitution in a conserved region that contains binding sites for interacting proteins. The mutation, which was found by next generation sequence analysis, was not present in the dbSNP, 1000 Genomes Project, or the Exome Variant Server databases. The authors stated that the same variant had been described by several laboratories, including ClinVar (<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=SCV000152660.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ClinVar\', \'domain\': \'ncbi.nlm.nih.gov\'})">SCV000152660.1</a>) and GeneDx (<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=SCV000242923.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ClinVar\', \'domain\': \'ncbi.nlm.nih.gov\'})">SCV000242923.2</a>), in patients with epilepsy, developmental delay, and intellectual disability, consistent with developmental and epileptic encephalopathy-13 (DEE13; <a href="/entry/614558">614558</a>). Functional studies of the variant were not performed by <a href="#1" class="mim-tip-reference" title="Anand, G., Collett-White, F., Orsini, A., Thomas, S., Jayapal, S., Trump, N., Zaiwalla, Z., Jayawant, S. <strong>Autosomal dominant SCN8A mutation with an unusually mild phenotype.</strong> Europ. J. Paediat. Neurol. 20: 761-765, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27210545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27210545</a>] [<a href="https://doi.org/10.1016/j.ejpn.2016.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27210545">Anand et al. (2016)</a>. The benign phenotype in the father and son suggested that they may carry additional variants in other genes that offer a protective effect. Sanger sequencing of the father did not show somatic mosaicism for the SCN8A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27210545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MYOCLONUS, FAMILIAL, 2 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, PRO1719ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1565934070 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565934070;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=rs1565934070" 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=rs1565934070" 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=RCV000761580 OR RCV003992384" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000761580, RCV003992384" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000761580...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a family with myoclonic epilepsy-2 (MYOCL2; <a href="/entry/618364">618364</a>), <a href="#25" class="mim-tip-reference" title="Wagnon, J. L., Mencacci, N. E., Barker, B. S., Wengert, E. R., Bhatia, K. P., Balint, B., Carecchio, M., Wood, N. W., Patel, M. K., Meisler, M. H. <strong>Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus.</strong> Hum. Mutat. 39: 965-969, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29726066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29726066</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29726066[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.23547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29726066">Wagnon et al. (2018)</a> identified a heterozygous c.5156C-G transversion (c.5156C-G, NM_014191.3) in the SCN8A gene, resulting in a pro1719-to-arg (P1719R) substitution in the conserved pore loop of domain IV that confers sodium selectivity to the channel. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family in those who agreed to testing. The variant was not found in the gnomAD database. In vitro functional expression studies in transfected neuron-derived cells showed that the mutation caused a partial loss of function, manifest as decreased inward sodium current, compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29726066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 COGNITIVE IMPAIRMENT WITHOUT CEREBELLAR ATAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, GLY964ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057521662 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057521662;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=rs1057521662" 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=rs1057521662" 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=RCV000439821 OR RCV000766191 OR RCV003992294" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000439821, RCV000766191, RCV003992294" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000439821...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old girl (patient 1) with cognitive impairment without cerebellar ataxia (CIAT; <a href="/entry/614306">614306</a>), <a href="#24" class="mim-tip-reference" title="Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., Swinkels, M. E. M., Patel, M. K., Meisler, M. H. <strong>Loss-of-function variants of SCN8A in intellectual disability without seizures.</strong> Neurol. Genet. 3: e170, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28702509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28702509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28702509[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/10.1212/NXG.0000000000000170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28702509">Wagnon et al. (2017)</a> identified a de novo heterozygous c.2890G-C transversion in the SCN8A gene, resulting in a gly964-to-arg (G964R) substitution at a highly conserved residue in transmembrane segment 6 of domain II. The mutation, which was found by exome sequencing, was not found in the ExAC database. The patient also carried a heterozygous frameshift variant (c.167delT) in the GJB2 gene (<a href="/entry/121011">121011</a>) that was inherited from an unaffected parent. In vitro functional expression studies in transfected cells showed that the G964R mutation caused a complete loss of channel activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28702509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 COGNITIVE IMPAIRMENT WITHOUT CEREBELLAR ATAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SCN8A, GLU1218LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555226823 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555226823;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=rs1555226823" 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=rs1555226823" 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=RCV000766192 OR RCV001240826" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000766192, RCV001240826" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000766192...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old boy (patient 2) with cognitive impairment and a history of ataxia (CIAT; <a href="/entry/614306">614306</a>), <a href="#24" class="mim-tip-reference" title="Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., Swinkels, M. E. M., Patel, M. K., Meisler, M. H. <strong>Loss-of-function variants of SCN8A in intellectual disability without seizures.</strong> Neurol. Genet. 3: e170, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28702509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28702509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28702509[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/10.1212/NXG.0000000000000170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28702509">Wagnon et al. (2017)</a> identified a de novo heterozygous c.3652G-A transition in the SCN8A gene, resulting in a glu1218-to-lys (E1218K) substitution at a highly conserved residue in transmembrane segment 1 of domain III. The mutation, which was found by exome sequencing, was not found in the ExAC database. The variant was not found in the unaffected mother; the father was not available for testing. The patient also carried a heterozygous missense variant (A174T) in the PDHA1 gene (<a href="/entry/300502">300502</a>) that was inherited from an unaffected grandparent. In vitro functional expression studies in transfected cells showed that the E1218K mutation caused a complete loss of channel activity. There was also a decreased amount of mutant protein, suggesting reduced stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28702509" 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="Anand2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anand, G., Collett-White, F., Orsini, A., Thomas, S., Jayapal, S., Trump, N., Zaiwalla, Z., Jayawant, S.
|
|
<strong>Autosomal dominant SCN8A mutation with an unusually mild phenotype.</strong>
|
|
Europ. J. Paediat. Neurol. 20: 761-765, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27210545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27210545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27210545" 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.ejpn.2016.04.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Blanchard2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J.
|
|
<strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong>
|
|
J. Med. Genet. 52: 330-337, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25725044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25725044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25725044[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=25725044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2014-102813" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Burgess1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., Meisler, M. H.
|
|
<strong>Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.</strong>
|
|
Nature Genet. 10: 461-465, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670495" 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/ng0895-461" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Carvill2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others.
|
|
<strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong>
|
|
Nature Genet. 45: 825-830, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[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=23708187" 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/ng.2646" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="de Kovel2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Kovel, C. G. F., Meisler, M. H., Brilstra, E. H., van Berkestijn, F. M. C., van't Slot, R., van Lieshout, S., Nijman, I. J., O'Brien, J. E., Hammer, M. F., Estacion, M., Waxman, S. G., Dib-Hajj, S. D., Koeleman, B. P. C.
|
|
<strong>Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.</strong>
|
|
Epilepsy Res. 108: 1511-1518, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25239001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25239001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25239001[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=25239001" 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.eplepsyres.2014.08.020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="De Repentigny2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Repentigny, Y., Cote, P. D., Pool, M., Bernier, G., Girard, S., Vidal, S. M., Kothary, R.
|
|
<strong>Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new allele of Scn8a.</strong>
|
|
Hum. Molec. Genet. 10: 1819-1827, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11532991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11532991</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11532991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.17.1819" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Drews2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Drews, V. L., Shi, K., de Haan, G., Meisler, M. H.
|
|
<strong>Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A.</strong>
|
|
Mammalian Genome 18: 723-731, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17924165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17924165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17924165[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=17924165" 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/s00335-007-9059-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Gardella2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gardella, E., Becker, F., Moller, R. S., Schubert, J., Lemke, J. R., Larsen, L. H. G., Eiberg, H., Nothnagel, M., Thiele, H., Altmuller, J., Syrbe, S., Merkenschlager, A., and 16 others.
|
|
<strong>Benign infantile seizure and paroxysmal dyskinesia caused by an SCN8A mutation.</strong>
|
|
Ann. Neurol. 79: 428-436, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26677014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26677014</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26677014" 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.24580" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Kearney2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kearney, J. A., Buchner, D. A., de Haan, G., Adamska, M., Levin, S. I., Furay, A. R., Albin, R. L., Jones, J. M., Montal, M., Stevens, M. J., Sprunger, L. K., Meisler, M. H.
|
|
<strong>Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Nav1.6).</strong>
|
|
Hum. Molec. Genet. 11: 2765-2775, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/11.22.2765" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kohrman1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kohrman, D. C., Harris, J. B., Meisler, M. H.
|
|
<strong>Mutation detection in the med and med(J) alleles of the sodium channel Scn8a: unusual splicing due to a minor class AT-AC intron.</strong>
|
|
J. Biol. Chem. 271: 17576-17581, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8663325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.271.29.17576" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kohrman1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kohrman, D. C., Plummer, N. W., Schuster, T., Jones, J. M., Jang, W., Burgess, D. L., Galt, J., Spear, B. T., Meisler, M. H.
|
|
<strong>Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.</strong>
|
|
Genomics 26: 171-177, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7601440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7601440</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7601440" 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(95)80198-u" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kohrman1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kohrman, D. C., Smith, M. R., Goldin, A. L., Harris, J., Meisler, M. H.
|
|
<strong>A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting.</strong>
|
|
J. Neurosci. 16: 5993-5999, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8815882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8815882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8815882[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=8815882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1523/JNEUROSCI.16-19-05993.1996" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Letko2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Letko, A., Dietschi, E., Nieburg, M., Jagannathan, V., Gurtner, C., Oevermann, A., Drogemuller, C.
|
|
<strong>A missense variant in SCN8A in Alpine Dachsbracke dogs affected by spinocerebellar ataxia.</strong>
|
|
Genes (Basel) 10: 362, 2019. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31083464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31083464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31083464[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=31083464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3390/genes10050362" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Lorincz2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lorincz, A., Nusser, Z.
|
|
<strong>Molecular identify of dendritic voltage-gated sodium channels.</strong>
|
|
Science 328: 906-909, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20466935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20466935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20466935[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=20466935" 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.1187958" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Martin2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martin, M. S., Tang, B., Papale, L. A., Yu, F. H., Catterall, W. A., Escayg, A.
|
|
<strong>The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy.</strong>
|
|
Hum. Molec. Genet. 16: 2892-2899, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddm248" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Meisler1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meisler, M. H., Sprunger, L. K., Plummer, N. W., Escayg, A., Jones, J. M.
|
|
<strong>Ion channel mutations in mouse models of inherited neurological disease.</strong>
|
|
Ann. Med. 29: 569-574, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9562526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9562526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9562526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3109/07853899709007484" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Ohba2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ohba, C., Kato, M., Takahashi, S., Lerman-Sagie, T., Lev, D., Terashima, H., Kubota, M., Kawawaki, H., Matsufuji, M., Kojima, Y., Tateno, A., Goldberg-Stern, H., and 10 others.
|
|
<strong>Early onset epileptic encephalopathy caused by de novo SCN8A mutations.</strong>
|
|
Epilepsia 55: 994-1000, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24888894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24888894</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24888894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/epi.12668" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Papale2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Papale, L. A., Beyer, B., Jones, J. M., Sharkey, L. M., Tufik, S., Epstein, M., Letts, V. A., Meisler, M. H., Frankel, W. N., Escayg, A.
|
|
<strong>Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice.</strong>
|
|
Hum. Molec. Genet. 18: 1633-1641, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19254928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19254928</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19254928[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=19254928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp081" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Plummer1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H.
|
|
<strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong>
|
|
Genomics 54: 287-296, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828131" 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.1998.5550" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Plummer1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Plummer, N. W., McBurney, M. W., Meisler, M. H.
|
|
<strong>Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.</strong>
|
|
J. Biol. Chem. 272: 24008-24015, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9295353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9295353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9295353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.272.38.24008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Sprunger1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H.
|
|
<strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong>
|
|
Hum. Molec. Genet. 8: 471-479, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949206</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9949206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/8.3.471" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Trudeau2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Trudeau, M. M., Dalton, J. C., Day, J. W., Ranum, L. P. W., Meisler, M. H.
|
|
<strong>Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. (Letter)</strong>
|
|
J. Med. Genet. 43: 527-530, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236810</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16236810[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=16236810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2005.035667" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Veeramah2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Veeramah, K. R., O'Brien, J. E., Meisler, M. H., Cheng, X., Dib-Hajj, S. D., Waxman, S. G., Talwar, D., Girirajan, S., Eichler, E. E., Restifo, L. L., Erickson, R. P., Hammer, M. F.
|
|
<strong>De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.</strong>
|
|
Am. J. Hum. Genet. 90: 502-512, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22365152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22365152</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22365152[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=22365152" 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.2012.01.006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Wagnon2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., Swinkels, M. E. M., Patel, M. K., Meisler, M. H.
|
|
<strong>Loss-of-function variants of SCN8A in intellectual disability without seizures.</strong>
|
|
Neurol. Genet. 3: e170, 2017. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28702509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28702509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28702509[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=28702509" 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/NXG.0000000000000170" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Wagnon2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wagnon, J. L., Mencacci, N. E., Barker, B. S., Wengert, E. R., Bhatia, K. P., Balint, B., Carecchio, M., Wood, N. W., Patel, M. K., Meisler, M. H.
|
|
<strong>Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus.</strong>
|
|
Hum. Mutat. 39: 965-969, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29726066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29726066</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29726066[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=29726066" 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.23547" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Yu2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., Spain, W. J., McKnight, G. S., Scheuer, T., Catterall, W. A.
|
|
<strong>Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.</strong>
|
|
Nature Neurosci. 9: 1142-1149, 2006. Note: Erratum: Nature Neurosci. 10: 134 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16921370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16921370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16921370" 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/nn1754" 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">
|
|
Alan F. Scott - updated : 07/29/2019
|
|
</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 : 03/25/2019<br>Cassandra L. Kniffin - updated : 03/21/2019<br>Cassandra L. Kniffin - updated : 08/18/2016<br>Cassandra L. Kniffin - updated : 6/8/2015<br>Cassandra L. Kniffin - updated : 12/9/2014<br>Cassandra L. Kniffin - updated : 9/22/2014<br>Cassandra L. Kniffin - updated : 8/15/2013<br>Cassandra L. Kniffin - updated : 3/28/2012<br>Cassandra L. Kniffin - updated : 10/31/2011<br>Ada Hamosh - updated : 5/27/2010<br>George E. Tiller - updated : 11/25/2009<br>Cassandra L. Kniffin - updated : 9/2/2009<br>Patricia A. Hartz - updated : 9/10/2008<br>Victor A. McKusick - updated : 7/5/2006<br>George E. Tiller - updated : 2/13/2004<br>George E. Tiller - updated : 2/5/2002<br>Carol A. Bocchini - updated : 5/30/2001<br>Michael J. Wright - updated : 2/5/2001<br>Victor A. McKusick - updated : 3/19/1999<br>Victor A. McKusick - updated : 11/30/1998<br>Victor A. McKusick - updated : 11/23/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 7/31/1995
|
|
</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 : 11/15/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
ckniffin : 03/08/2023<br>carol : 01/18/2023<br>mgross : 01/17/2023<br>alopez : 12/03/2020<br>alopez : 10/19/2020<br>joanna : 10/09/2020<br>carol : 09/01/2020<br>alopez : 07/29/2019<br>carol : 03/29/2019<br>ckniffin : 03/25/2019<br>carol : 03/21/2019<br>ckniffin : 03/21/2019<br>carol : 02/28/2017<br>carol : 08/22/2016<br>ckniffin : 08/18/2016<br>carol : 11/25/2015<br>carol : 6/10/2015<br>mcolton : 6/9/2015<br>ckniffin : 6/8/2015<br>carol : 12/11/2014<br>mcolton : 12/10/2014<br>ckniffin : 12/9/2014<br>carol : 11/26/2014<br>carol : 9/22/2014<br>ckniffin : 9/22/2014<br>carol : 8/19/2013<br>ckniffin : 8/15/2013<br>carol : 5/29/2013<br>mgross : 4/13/2012<br>carol : 4/2/2012<br>ckniffin : 3/28/2012<br>carol : 10/31/2011<br>carol : 10/31/2011<br>ckniffin : 10/31/2011<br>joanna : 7/27/2010<br>carol : 6/11/2010<br>alopez : 6/1/2010<br>terry : 5/27/2010<br>wwang : 12/4/2009<br>terry : 11/25/2009<br>wwang : 9/10/2009<br>ckniffin : 9/2/2009<br>mgross : 9/10/2008<br>terry : 9/10/2008<br>carol : 10/4/2006<br>alopez : 7/10/2006<br>alopez : 7/10/2006<br>alopez : 7/7/2006<br>terry : 7/5/2006<br>cwells : 2/13/2004<br>cwells : 2/14/2002<br>cwells : 2/5/2002<br>cwells : 2/5/2002<br>carol : 6/14/2001<br>carol : 5/30/2001<br>alopez : 2/5/2001<br>kayiaros : 7/8/1999<br>carol : 7/7/1999<br>terry : 4/29/1999<br>mgross : 3/29/1999<br>mgross : 3/26/1999<br>terry : 3/19/1999<br>carol : 11/30/1998<br>carol : 11/23/1998<br>terry : 9/6/1995<br>mark : 7/31/1995
|
|
</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> 600702
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 8; SCN8A
|
|
|
|
</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">
|
|
SODIUM CHANNEL, VOLTAGE-GATED, TYPE VIII, ALPHA SUBUNIT<br />
|
|
NAV1.6
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SCN8A</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 765170001;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 12q13.13
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 12:51,591,233-51,812,864 </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="4">
|
|
<span class="mim-font">
|
|
12q13.13
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Myoclonus, familial, 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
618364
|
|
</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">
|
|
Cognitive impairment with or without cerebellar ataxia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614306
|
|
</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">
|
|
Developmental and epileptic encephalopathy 13
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614558
|
|
</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">
|
|
Seizures, benign familial infantile, 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617080
|
|
</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>Voltage-dependent sodium channels, such as SCN8A, are responsible for the initial membrane depolarization that occurs during generation of action potentials in most electrically excitable cells (Plummer et al., 1998). </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>Plummer et al. (1998) isolated and sequenced genomic fragments containing the exons of a novel human voltage-gated sodium channel designated SCN8A. SCN8A encodes a 1,980-amino acid protein that shares close to 99% sequence identity with the mouse protein. It contains several consensus sites for phosphorylation of serine and threonine residues that are also conserved in other sodium channel family members. </p><p>Plummer et al. (1997) identified 2 alternatively spliced exons of SCN8A, 18N and 18A, that encode transmembrane segments S3 and S4 in domain III. Exon 18N is expressed in fetal brain and nonneuronal tissues. Transcripts with exon 18N have a conserved in-frame stop codon that predicts the synthesis of a truncated, 2-domain protein. The proportion of transcripts containing exon 18N is highest in mouse fetal brain between embryonic day (E) 12.5 and E14.5; at E18.5 and later, the 18A transcript predominates. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Plummer et al. (1998) determined that the SCN8A gene contains 28 exons and identified an additional pair of alternatively spliced exons, 5N and 5A, that encode transmembrane segments of domain I. Exons 5N and 5A differ by a single amino acid difference at position 7. Plummer et al. (1998) also found that major and minor protein transcripts are generated by 2 alternative splice donor sites for exon 10B; the minor transcript contains 11 extra amino acids. </p><p>Drews et al. (2007) identified 4 untranslated 5-prime exons, which they designated 1a through 1d, in the mouse and human SCN8A genes. These exons are mutually exclusive, and each is alternatively spliced to the first coding exon. Exon 1a overlaps with an inserted LINE element, and the 70-kb interval between the 5-prime noncoding exons and the first coding exon contains 58% repetitive elements and simple repeats. The Scn8a genes of lower vertebrates contain only a single 5-prime untranslated exon that corresponds to mouse and human exon 1c. Exon 1c contains conserved functional YY1 (600013) and REST (600571) sites. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Active invasion of the dendritic tree by action potentials generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells, this action potential back-propagation is supported by dendritic voltage-gated sodium channels. Using a highly sensitive electron microscopic immunogold technique, Lorincz and Nusser (2010) revealed the presence of the Nav1.6 subunit in hippocampal CA1 pyramidal cell proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Lorincz and Nusser (2010) concluded that their results revealed the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kohrman et al. (1995) assigned the mouse Scn8a gene to chromosome 15 by interspecific backcross analysis and the human SCN8A gene to chromosome 12 by hybridization to a somatic cell hybrid mapping panel. Burgess et al. (1995) mapped the human homolog to 12q13 by fluorescence in situ hybridization. By physical mapping on a YAC contig, Plummer et al. (1998) localized the SCN8A gene to 12q13.1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Cognitive Impairment with or without Cerebellar Ataxia</em></strong></p><p>
|
|
Because SCN8A is widely expressed in neurons of the central and peripheral nervous systems, and because mutations in the mouse ortholog result in ataxia and other movement disorders, Trudeau et al. (2006) screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia. They found a 2-bp deletion in exon 24 (600702.0001) in a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia (CIAT; 614306). Three additional family members who were heterozygous for this mutation exhibited milder cognitive behavioral deficits including attention deficit-hyperactivity disorder (ADHD; 143465). No additional occurrence of this mutation was observed in 625 unrelated DNA samples (1,250 chromosomes). </p><p>In 2 unrelated children with CIAT, Wagnon et al. (2017) identified de novo heterozygous missense mutations in the SCN8A gene (G964R, 600702.0013 and E1218K, 600702.0014). The mutations, which were found by exome sequencing, occurred at highly conserved residues in transmembrane domains. In vitro functional expression studies in transfected cells showed that both mutations caused a complete loss of channel activity. Wagnon et al. (2017) suggested that loss of neuronal activity due to the mutation may alter the dynamics of synaptic plasticity during maturation and lead to aberrant cerebral circuitry and intellectual disability. </p><p><strong><em>Developmental and Epileptic Encephalopathy 13</em></strong></p><p>
|
|
In a girl with developmental and epileptic encephalopathy-13 (DEE13; 614558), Veeramah et al. (2012) identified a de novo heterozygous mutation in the SCN8A gene (N1768D; 600702.0002). In vitro functional expression studies showed that the mutation caused a dominant gain-of-function effect, with neuronal hyperexcitability, persistent sodium currents, incomplete channel inactivation, increased spontaneous firing, paroxysmal-depolarizing-shift-like complexes, and an increased firing frequency. </p><p>Carvill et al. (2013) identified a heterozygous mutation in the SCN8A gene (L1290V; 600702.0003) in a boy with DEE13. The mutation was inherited from his father, who was found to be somatic mosaic for the mutation. No further clinical information was provided. The patient was part of a cohort of 500 cases of epileptic encephalopathy who underwent sequencing of candidate genes; he was the only patient found to carry an SCN8A mutation. </p><p>In 7 unrelated patients with DEE13, Ohba et al. (2014) identified 7 different de novo heterozygous missense mutations in the SCN8A gene (see, e.g., 600702.0004-600702.0006). Whole-exome or targeted capture sequencing detected mutations in 6 (10%) of 60 patients with early-onset epileptic encephalopathy and in 1 (16.7%) of 6 patients diagnosed clinically with malignant migrating partial seizures in infancy (MMPSI). Functional studies of the variants were not performed, but all occurred at highly conserved residues scattered throughout the gene with variable predicted effects. There were no apparent genotype-phenotype correlations. </p><p><strong><em>Benign Familial Infantile Seizures 5</em></strong></p><p>
|
|
In 16 patients from 3 unrelated families with benign familial infantile seizures-5 (BFIS5; 617080), Gardella et al. (2016) identified a heterozygous missense mutation in the SCN8A gene (E1483K; 600702.0010). The variant, which was found by exome sequencing in 2 of the families and confirmed by Sanger sequencing, segregated with the disorder in all 3 families, with evidence of incomplete penetrance. Linkage analysis excluded a founder effect. Although functional studies of the mutation were not performed, Gardella et al. (2016) postulated that it caused a small gain-of-function effect resulting from impaired channel inactivation. </p><p>In a father and son with BFIS5, Anand et al. (2016) identified a heterozygous missense mutation in the SCN8A gene (N1877S; 600702.0011). Functional studies of the variant were not performed, but Anand et al. (2016) noted that the same variant has been identified in patients with a more severe disorder, including developmental delay, epileptic encephalopathy, and intellectual disability (DEE13). The benign phenotype in the father and son suggested that they may carry additional variants in other genes that offer a protective effect. Sanger sequencing excluded somatic mosaicism for the SCN8A mutation in the father. </p><p><strong><em>Familial Myoclonic Epilepsy 2</em></strong></p><p>
|
|
In 3 affected members of a family with myoclonic epilepsy-2 (MYOCL2; 618364), Wagnon et al. (2018) identified a heterozygous missense mutation in the SCN8A gene (P1719R; 600702.0012). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family in those who agreed to testing. In vitro functional expression studies in transfected neuron-derived cells showed that the mutation caused a partial loss of function, manifest as decreased inward sodium current compared to controls. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with developmental delay, impaired intellectual development, and early-onset seizures, Blanchard et al. (2015) identified 2 different de novo heterozygous missense mutations in the SCN8A gene (N984K, 600702.0008 and G1451S, 600702.0009). The patients were ascertained from a cohort of 500 patients with intellectual disability and 100 patients with a movement disorder who underwent exome sequencing. In vitro functional expression studies showed that the N984K mutation resulted in increased channel opening and increased neuronal excitability, consistent with a gain of function, whereas the G1451S mutation resulted in decreased current density, consistent with a loss of function. The patient with the N984K mutation had onset of intractable seizures at age 6 weeks and severe developmental delay with no speech and inability to sit independently at age 7 years; the patient with the G1451S mutation had a slightly less severe phenotype, with onset of seizures at age 18 months, moderate to severe developmental delay, spastic tetraplegia, ataxia, and nystagmus with cerebellar atrophy at age 33 years. Blanchard et al. (2015) concluded that SCN8A mutations resulting in a gain of function may result in a more severe phenotype, but noted that the G1451S mutation may also have some gain-of-function effects that were not detected in the cellular assay. A third unrelated patient with severe developmental delay (IQ of 55), dysmorphic features, and no seizures had a heterozygous D58N variant in the SCN8A gene, but functional studies showed normal SCN8A channel activity, suggesting that the variant may not be pathogenic. This patient also carried a heterozygous R95Q variant in the RING1 gene (602045), but functional studies of the variant were not performed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The mouse neurologic mutant 'motor endplate disease' (med) is characterized by early-onset progressive paralysis of the hindlimbs, severe muscle atrophy, degeneration of Purkinje cells, and juvenile lethality. Burgess et al. (1995) isolated a voltage-gated sodium channel gene, Scn8a, from the flanking region of a transgene-induced allele of med. Scn8a is expressed in brain and spinal cord but not in skeletal muscle or heart, and encodes a predicted protein of 1,732 amino acids. An intragenic deletion at the site of transgene insertion resulted in loss of expression. The gene is closely related to other sodium channel alpha subunits: SCN1A (182389), SCN2A (182390), SCN3A (182391), SCN4A (603967), SCN5A (600163), and SCN6A (182392). Kohrman et al. (1996) identified a missense mutation in Scn8a that is associated with cerebellar ataxia in the 'jolting' mutant, a mild allele of the med locus. Kohrman et al. (1996) described the molecular changes in Scn8a underlying 2 other spontaneous mutants, med and med(J). The med mutation was caused by insertion of a truncated LINE element into exon 2 of Scn8a. The med transcript was spliced from exon 1 to a cryptic acceptor site in intron 2. In the med(J) allele, a 4-bp deletion within 5-prime donor site of exon 3 resulted in splicing from exon 1 to exon 4. Both mutant transcripts altered the reading frame with premature stop codons close to the N terminus of the protein. Loss of Scn8a expression resulted in progressive paralysis and early death. Intron 2 of Scn8a is flanked by minor class AT-AC splice sites. The observed splicing patterns of the med and med(J) mutant transcripts provided evidence for preferential in vivo splicing between donor and acceptor sites of the same class. The apparent functional incompatibility may be a consequence of the different composition of spliceosomes bound to major and minor splice sites. The unusual pattern of exon skipping in these mutant identified Scn8a as a member of a small group of genes containing introns with nonstandard AT-AC splice sites. AT-AC introns are processed by alternative splicing machinery that includes U11 and U12 (RNU12; 620204) snRNPs. Meisler et al. (1997) reviewed how the analysis of molecular defects in mouse mutants can identify candidate genes for human neurologic disorders, as illustrated by Scn8a among other genes. </p><p>Sprunger et al. (1999) studied the mouse mutant med(J), which contains a splice site mutation in the neuronal sodium channel Scn8a that results in a very low level of expression. On the C57BL/6J genetic background, med(J) homozygotes exhibited progressive paralysis and juvenile lethality. The C3H genetic background had an ameliorating effect, producing viable adults with a novel dystonic phenotype. The dystonic mice exhibited movement-induced, sustained abnormal postures of the trunk and limbs. Sprunger et al. (1999) mapped a dominant modifier locus responsible for the difference between strains to a 4.5 +/- 1.3-cM interval on mouse chromosome 3. These findings established a role for ion channels in dystonia and demonstrated the impact of genetic background on its severity and progression. This new model suggested to Sprunger et al. (1999) that SCN8A on 12q13 and SCNM1 (which by comparative mapping is presumably located on 1p21-q21) may contribute to human inherited dystonia. </p><p>The dystonia demonstrated by Sprunger et al. (1999) in association with the Scn8a mutation was the first to be related to mutation in an ion channel. Furthermore, the med(J) mouse differed from other animal models with dystonia in that the condition persisted to adulthood and was not associated with neurodegeneration. Sprunger et al. (1999) suggested that the med(J) mutation should be classified as a hypomorphic allele because a low level of full-length Scn8a transcripts was demonstrated in homozygotes, indicating normal splicing at low efficiency. Homozygotes for null alleles of Scn8a could not survive even in the presence of 2 copies of the Scnm1(H) modifier allele. Thus, prevention of paralysis and survival to adulthood required both a low level of wildtype transcript and at least 1 copy of the dominant allele of Scnm1. C57BL/6J carries a recessive allele of Scmn1 that, in combination with a hypomorphic level of Scn8a, resulted in paralysis and lethality. </p><p>De Repentigny et al. (2001) described a spontaneous autosomal recessive mutation in the mouse, which they termed 'degenerating muscle' (dmu), that is characterized by skeletal and cardiac muscle degeneration. Dmu mice are weak and have great difficulty in moving due to muscle atrophy and wasting in the hindquarters. Histopathologic observations and ultrastructural analysis revealed muscle degeneration in both skeletal and cardiac muscle, but no abnormalities in sciatic nerves. Using linkage analysis, the authors mapped the dmu locus to the distal portion of mouse chromosome 15 in a region syntenic to human chromosome 12q13. Intact transcripts for Scn8a were present in dmu mice, but their levels were dramatically reduced. Furthermore, genetic complementation crosses between dmu and med mice revealed that they are allelic. The authors concluded that at least a portion of the dmu phenotype may be caused by a downregulation of Scn8a. </p><p>Kearney et al. (2002) described a sensitive allele of the unlinked modifier locus, Scnm1, which results in juvenile lethality in C57BL/6J mice carrying the med(J) mutation. The modifier acts on the splicing efficiency of the mutant splice donor site in Scn8a, and mutant mice display either 90% or 95% reduction in the proportion of correctly spliced mRNA, depending on modifier genotype. The abundance of the channel protein, NaV1.6, is also reduced by an order of magnitude in med(J) mice, resulting in delayed maturation of nodes of Ranvier, slowed nerve conduction velocity, reduced muscle mass, and reduction of brain metabolic activity. </p><p>Martin et al. (2007) showed that Scn8a(med) and Scn8a(med-jo) mice, which carry the heterozygous 'jolting' point mutation, were more resistant to pharmacologically induced seizures than wildtype littermates, suggesting that altered Scn8a function reduces neuronal excitability. They also showed that the seizure severity of heterozygous Scn1a +/- mice (see Yu et al., 2006), which is a mouse model for severe myoclonic epilepsy of infancy (SMEI; 607208), was ameliorated by the Scn8a(med-jo) allele. Double-heterozygous Scn1a +/- and Scn8a +/(med-jo) mice had seizure thresholds that were comparable to wildtype littermates, and the Scn8a(med-jo) allele was also able to rescue the premature lethality of Scn1a +/- mice and extended the life span of Scn1a -/- mice. The authors hypothesized that the opposing effects of Scn1a and Scn8a dysfunction on seizure thresholds result from differences in the cell types that are influenced by the respective sodium channel subtypes. Scn1a mutants result in reduced sodium currents in inhibitory GABAergic interneurons of the hippocampus and cortex, whereas Scn8a mutants affect excitatory pyramidal cells of the hippocampus and cortex, suggesting that reduced excitability of these cells may underlie the elevated seizure resistance of Scn8a-mutant mice. Martin et al. (2007) suggested that their results demonstrated that genetic interactions can alter seizure severity, and supported the hypothesis that genetic modifiers, including the SCN8A gene, contribute to the clinical variability observed in SMEI and GEFS+. </p><p>By ENU-induced mutagenesis screen in mice, Papale et al. (2009) generated a val929-to-phe (V929F) mutation in the Scn8a gene. This residue in the pore loop of domain 2 is evolutionarily conserved. Electroencephalography (EEG) revealed well-defined spike-wave discharges (SWD), the hallmark of absence epilepsy (see 600131), in V929F-heterozygous mice and in mice heterozygous for either the Scn8a(med) or Scn8a(med-jo) mutations. Genetic background had a significant effect on SWD, with mutants on the C3HeB/FeJ strain showing a higher incidence than on C57BL/6J. Papale et al. (2009) suggested that the SCN8A gene may be a candidate gene for absence epilepsy in humans. </p><p>Letko et al. (2019) identified a homozygous missense variant (gly1633 to val, G1633V) in the SCN8A gene in 4 Alpine Dachsbracke dogs affected with spinocerebellar ataxia characterized by ataxia, tremor, loss of balance and axonal degeneration. Pathogenicity of the mutation was supported by genotyping studies in over 200 dogs of this breed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>14 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, 2-BP DEL, 5156CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776703,
|
|
|
|
|
|
gnomAD: rs587776703,
|
|
|
|
|
|
ClinVar: RCV000009467, RCV004589503
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia (CIAT; 614306), Trudeau et al. (2006) identified heterozygosity for a 2-bp deletion in exon 24 of the SCN8A gene, which introduced a translation termination codon into the pore loop of domain 4, resulting in removal of the C-terminal cytoplasmic domain and predicting loss of channel function (Pro1719ArgfsTer6). The authors stated in the text that the deletion removed nucleotides 5156 and 5157, and in Figure 1 that it removed nucleotides 5157 and 5158. Three additional heterozygous family members exhibited milder cognitive and behavioral deficits including attention deficit-hyperactivity disorder (ADHD; 143465). Trudeau et al. (2006) noted that it was unclear whether the relatives of the proband had a milder version of the neurologic abnormalities seen in the proband due to haploinsufficiency for SCN8A, or if the proband's symptoms were caused by an unrelated developmental disorder. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ASN1768ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs202151337,
|
|
|
|
|
|
|
|
ClinVar: RCV000023031, RCV001230237, RCV003992161
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with developmental and epileptic encephalopathy-13 (DEE13; 614558), Veeramah et al. (2012) identified a de novo heterozygous c.5302A-G transition (c.5302A-G, NM_014191.2) in the SCN8A gene, resulting in an asn1768-to-asp (N1768D) substitution in a highly conserved residue in the final transmembrane segment adjacent to the C-terminal cytoplasmic domain. The mutation was identified by whole-genome sequencing. Expression of the mutant protein in a neuronal cell line showed that it caused persistent sodium currents, incomplete channel inactivation, and a depolarizing shift in the voltage dependence of steady-state fast inactivation. Current-clamp analysis in rat hippocampal neurons transfected with the mutant protein showed increased spontaneous firing, paroxysmal-depolarizing-shift-like complexes, and an increased firing frequency, consistent with a dominant gain-of-function phenotype. All of these studies were consistent with neuronal hyperexcitability. Whole-genome sequencing also identified putative recessive variants in the NRP2 (602070) and UNC13C (614568) genes in the proband, which may have contributed to the phenotype. The patient developed refractory generalized seizures at age 6 months. At age 4 years, the seizure phenotype changed to epileptic spasms, followed by regression of speech and language skills. She also had developmental delay, intellectual disability, autism, hypotonia, and difficulties with coordination and balance. Initial electroencephalogram (EEG) showed bifrontal spikes and brief bursts of generalized spike-wave activity. Later EEG showed diffuse slowing, multifocal spikes, and frontally predominant generalized spikes. Brain MRI was normal. The patient died suddenly at age 15 years. There was no family history of a similar disorder. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, LEU1290VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514738,
|
|
|
|
|
|
|
|
ClinVar: RCV000054506, RCV003992171
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy (patient T2939) with developmental and epileptic encephalopathy-13 (DEE13; 614558), Carvill et al. (2013) identified a heterozygous c.3868C-G transversion (c.3868C-G, NM_001177984.2) in the SCN8A gene, resulting in a leu1290-to-val (L1290V) substitution. The patient had onset of seizures at age 18 months. The mutation was inherited from the father, who was found to be somatic mosaic for the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ARG1617GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777721,
|
|
|
|
|
|
|
|
ClinVar: RCV000144154, RCV000522954, RCV000636307, RCV000678845, RCV001266283, RCV003992195
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old Japanese girl (patient 4) with developmental and epileptic encephalopathy-13 (DEE13; 614558), Ohba et al. (2014) identified a de novo heterozygous c.4850G-A transition (c.4850G-A, NM_014191.3) in the SCN8A gene, resulting in an arg1617-to-gln (R1617Q) substitution at a highly conserved residue in the S4 transmembrane segment that plays a role in voltage sensing. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of seizures at 3 months of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ASN1466LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777722,
|
|
|
|
|
|
|
|
ClinVar: RCV000144155
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Japanese boy (patient 1) with developmental and epileptic encephalopathy-13 (DEE13; 614558), Ohba et al. (2014) identified a de novo heterozygous c.4398C-A transversion (c.4398C-A, NM_014191.3) in the SCN8A gene, resulting in an asn1466-to-lys (N1466K) substitution at a highly conserved residue in the linker region between domains III and IV that forms an inactivation gate. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of intractable seizures on day 3 of life. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ASN1466THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777723,
|
|
|
|
|
|
|
|
ClinVar: RCV000144156
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Israeli boy (patient 5) with developmental and epileptic encephalopathy-13 (DEE13; 614558), Ohba et al. (2014) identified a de novo heterozygous c.4397A-C transversion (c.4397A-C, NM_014191.3) in the SCN8A gene, resulting in an asn1466-to-thr (N1466T) substitution at a highly conserved residue in the linker region between domains III and IV that forms an inactivation gate. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Sequencing Project database or in 408 in-house control exomes. Functional studies of the variant were not performed. The patient had onset of seizures at 4 months of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ARG223GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs672601319,
|
|
|
|
|
|
|
|
ClinVar: RCV000149436
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old girl with developmental and epileptic encephalopathy-13 (DEE13; 614558), de Kovel et al. (2014) identified a de novo heterozygous c.667A-G transition in the SCN8A gene, resulting in an arg223-to-gly (R223G) substitution at a highly conserved residue in the voltage-sensing transmembrane segment 4 of domain 1 (D1S4). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. In vitro cellular functional expression studies showed that the mutant protein had significantly reduced stability (about 20% of wildtype) and that the mutant channel had reduced peak current amplitude (20% of wildtype) at 37 degrees C. There was a 3-fold increase in the ramp current at 30 degrees C, but this was still a significant reduction in terms of absolute current levels. The findings were consistent with a loss-of-function effect. De Kovel et al. (2014) noted that SCN8A is expressed in inhibitory neurons, where a loss of function may yield an epileptic phenotype. The patient had onset of seizures at 6 months of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ASN984LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs876657399,
|
|
|
|
|
|
|
|
ClinVar: RCV000172909, RCV001003602, RCV003992211
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old girl with developmental and epileptic encephalopathy-13 (DEE13; 614558), Blanchard et al. (2015) identified a de novo heterozygous c.2952C-G transversion (c.2952C-G, NM_014191.2) in the SCN8A gene, resulting in an asn984-to-lys (N984K) substitution at a highly conserved residue adjacent to the transmembrane segment of the channel. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies in HEK293 cells showed that the mutation caused a 10-mV hyperpolarization shift, predicting premature channel opening and neuronal hyperactivity. The findings were consistent with a gain of function. The patient had onset of intractable seizures at 6 weeks of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, GLY1451SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs863223345,
|
|
|
|
|
|
|
|
ClinVar: RCV000172910, RCV000517164, RCV001380064, RCV002516572, RCV003320591, RCV003992212
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 33-year-old man with developmental and epileptic encephalopathy-13 (DEE13; 614558), Blanchard et al. (2015) identified a de novo heterozygous c.4351G-A transition (c.4351G-A, NM_014191.2) in the SCN8A gene, resulting in a gly1451-to-ser (G1451S) substitution at a conserved residue in transmembrane segment D3S6. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies in HEK293 cells showed that the mutation caused a 10-fold decrease in current density compared to wildtype, consistent with a loss of function. However, Blanchard et al. (2015) postulated that the mutant protein may also have a dominant effect. The patient had onset of seizures at 18 months of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SEIZURES, BENIGN FAMILIAL INFANTILE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, GLU1483LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs879255652,
|
|
|
|
|
|
|
|
ClinVar: RCV000239671, RCV001293365, RCV001556220, RCV002226427, RCV002518547, RCV003992245
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 16 patients from 3 unrelated families with benign familial infantile seizures-5 (BFIS5; 617080), Gardella et al. (2016) identified a heterozygous c.4447G-A transition in the SCN8A gene, resulting in a glu1483-to-lys (E1483K) substitution at a highly conserved residue in the intracellular loop between domains III and IV. The variant, which was found by exome sequencing in 2 of the families and confirmed by Sanger sequencing, segregated with the disorder in all 3 families, with evidence of incomplete penetrance. The mutation was not found in the dbSNP (build 138), 1000 Genomes Project, Exome Variant Server, or ExAC databases. Linkage analysis excluded a founder effect. Although functional studies of the mutation were not performed, Gardella et al. (2016) postulated that it caused a small gain-of-function effect resulting from impaired channel inactivation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SEIZURES, BENIGN FAMILIAL INFANTILE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, ASN1877SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587780455,
|
|
|
|
|
|
|
|
ClinVar: RCV000118288, RCV000239630, RCV000239702, RCV000416967, RCV000467598, RCV002274920, RCV003992186
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and son with benign familial infantile seizures-5 (BFIS5; 617080), Anand et al. (2016) identified a heterozygous c.5630A-G transition (c.5630A-G, NM_014191.3) in the SCN8A gene, resulting in an asn1877-to-ser (N1877S) substitution in a conserved region that contains binding sites for interacting proteins. The mutation, which was found by next generation sequence analysis, was not present in the dbSNP, 1000 Genomes Project, or the Exome Variant Server databases. The authors stated that the same variant had been described by several laboratories, including ClinVar (SCV000152660.1) and GeneDx (SCV000242923.2), in patients with epilepsy, developmental delay, and intellectual disability, consistent with developmental and epileptic encephalopathy-13 (DEE13; 614558). Functional studies of the variant were not performed by Anand et al. (2016). The benign phenotype in the father and son suggested that they may carry additional variants in other genes that offer a protective effect. Sanger sequencing of the father did not show somatic mosaicism for the SCN8A mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MYOCLONUS, FAMILIAL, 2 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, PRO1719ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1565934070,
|
|
|
|
|
|
|
|
ClinVar: RCV000761580, RCV003992384
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a family with myoclonic epilepsy-2 (MYOCL2; 618364), Wagnon et al. (2018) identified a heterozygous c.5156C-G transversion (c.5156C-G, NM_014191.3) in the SCN8A gene, resulting in a pro1719-to-arg (P1719R) substitution in the conserved pore loop of domain IV that confers sodium selectivity to the channel. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family in those who agreed to testing. The variant was not found in the gnomAD database. In vitro functional expression studies in transfected neuron-derived cells showed that the mutation caused a partial loss of function, manifest as decreased inward sodium current, compared to controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 COGNITIVE IMPAIRMENT WITHOUT CEREBELLAR ATAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, GLY964ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057521662,
|
|
|
|
|
|
|
|
ClinVar: RCV000439821, RCV000766191, RCV003992294
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old girl (patient 1) with cognitive impairment without cerebellar ataxia (CIAT; 614306), Wagnon et al. (2017) identified a de novo heterozygous c.2890G-C transversion in the SCN8A gene, resulting in a gly964-to-arg (G964R) substitution at a highly conserved residue in transmembrane segment 6 of domain II. The mutation, which was found by exome sequencing, was not found in the ExAC database. The patient also carried a heterozygous frameshift variant (c.167delT) in the GJB2 gene (121011) that was inherited from an unaffected parent. In vitro functional expression studies in transfected cells showed that the G964R mutation caused a complete loss of channel activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 COGNITIVE IMPAIRMENT WITHOUT CEREBELLAR ATAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN8A, GLU1218LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555226823,
|
|
|
|
|
|
|
|
ClinVar: RCV000766192, RCV001240826
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old boy (patient 2) with cognitive impairment and a history of ataxia (CIAT; 614306), Wagnon et al. (2017) identified a de novo heterozygous c.3652G-A transition in the SCN8A gene, resulting in a glu1218-to-lys (E1218K) substitution at a highly conserved residue in transmembrane segment 1 of domain III. The mutation, which was found by exome sequencing, was not found in the ExAC database. The variant was not found in the unaffected mother; the father was not available for testing. The patient also carried a heterozygous missense variant (A174T) in the PDHA1 gene (300502) that was inherited from an unaffected grandparent. In vitro functional expression studies in transfected cells showed that the E1218K mutation caused a complete loss of channel activity. There was also a decreased amount of mutant protein, suggesting reduced stability. </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">
|
|
Anand, G., Collett-White, F., Orsini, A., Thomas, S., Jayapal, S., Trump, N., Zaiwalla, Z., Jayawant, S.
|
|
<strong>Autosomal dominant SCN8A mutation with an unusually mild phenotype.</strong>
|
|
Europ. J. Paediat. Neurol. 20: 761-765, 2016.
|
|
|
|
|
|
[PubMed: 27210545]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ejpn.2016.04.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib-Hajji, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P., Praamstra, P., Nicolai, J., Yntema, H. G., Bindels, R. J. M., Meisler, M. H., Kamsteeg, E.-J.
|
|
<strong>De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.</strong>
|
|
J. Med. Genet. 52: 330-337, 2015.
|
|
|
|
|
|
[PubMed: 25725044]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2014-102813]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., Meisler, M. H.
|
|
<strong>Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.</strong>
|
|
Nature Genet. 10: 461-465, 1995.
|
|
|
|
|
|
[PubMed: 7670495]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0895-461]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others.
|
|
<strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong>
|
|
Nature Genet. 45: 825-830, 2013.
|
|
|
|
|
|
[PubMed: 23708187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2646]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Kovel, C. G. F., Meisler, M. H., Brilstra, E. H., van Berkestijn, F. M. C., van't Slot, R., van Lieshout, S., Nijman, I. J., O'Brien, J. E., Hammer, M. F., Estacion, M., Waxman, S. G., Dib-Hajj, S. D., Koeleman, B. P. C.
|
|
<strong>Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.</strong>
|
|
Epilepsy Res. 108: 1511-1518, 2014.
|
|
|
|
|
|
[PubMed: 25239001]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.eplepsyres.2014.08.020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Repentigny, Y., Cote, P. D., Pool, M., Bernier, G., Girard, S., Vidal, S. M., Kothary, R.
|
|
<strong>Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new allele of Scn8a.</strong>
|
|
Hum. Molec. Genet. 10: 1819-1827, 2001.
|
|
|
|
|
|
[PubMed: 11532991]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.17.1819]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Drews, V. L., Shi, K., de Haan, G., Meisler, M. H.
|
|
<strong>Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A.</strong>
|
|
Mammalian Genome 18: 723-731, 2007.
|
|
|
|
|
|
[PubMed: 17924165]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00335-007-9059-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gardella, E., Becker, F., Moller, R. S., Schubert, J., Lemke, J. R., Larsen, L. H. G., Eiberg, H., Nothnagel, M., Thiele, H., Altmuller, J., Syrbe, S., Merkenschlager, A., and 16 others.
|
|
<strong>Benign infantile seizure and paroxysmal dyskinesia caused by an SCN8A mutation.</strong>
|
|
Ann. Neurol. 79: 428-436, 2016.
|
|
|
|
|
|
[PubMed: 26677014]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.24580]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kearney, J. A., Buchner, D. A., de Haan, G., Adamska, M., Levin, S. I., Furay, A. R., Albin, R. L., Jones, J. M., Montal, M., Stevens, M. J., Sprunger, L. K., Meisler, M. H.
|
|
<strong>Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Nav1.6).</strong>
|
|
Hum. Molec. Genet. 11: 2765-2775, 2002.
|
|
|
|
|
|
[PubMed: 12374766]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.22.2765]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kohrman, D. C., Harris, J. B., Meisler, M. H.
|
|
<strong>Mutation detection in the med and med(J) alleles of the sodium channel Scn8a: unusual splicing due to a minor class AT-AC intron.</strong>
|
|
J. Biol. Chem. 271: 17576-17581, 1996.
|
|
|
|
|
|
[PubMed: 8663325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.271.29.17576]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kohrman, D. C., Plummer, N. W., Schuster, T., Jones, J. M., Jang, W., Burgess, D. L., Galt, J., Spear, B. T., Meisler, M. H.
|
|
<strong>Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.</strong>
|
|
Genomics 26: 171-177, 1995.
|
|
|
|
|
|
[PubMed: 7601440]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80198-u]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kohrman, D. C., Smith, M. R., Goldin, A. L., Harris, J., Meisler, M. H.
|
|
<strong>A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting.</strong>
|
|
J. Neurosci. 16: 5993-5999, 1996.
|
|
|
|
|
|
[PubMed: 8815882]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1523/JNEUROSCI.16-19-05993.1996]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Letko, A., Dietschi, E., Nieburg, M., Jagannathan, V., Gurtner, C., Oevermann, A., Drogemuller, C.
|
|
<strong>A missense variant in SCN8A in Alpine Dachsbracke dogs affected by spinocerebellar ataxia.</strong>
|
|
Genes (Basel) 10: 362, 2019. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 31083464]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3390/genes10050362]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lorincz, A., Nusser, Z.
|
|
<strong>Molecular identify of dendritic voltage-gated sodium channels.</strong>
|
|
Science 328: 906-909, 2010.
|
|
|
|
|
|
[PubMed: 20466935]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1187958]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martin, M. S., Tang, B., Papale, L. A., Yu, F. H., Catterall, W. A., Escayg, A.
|
|
<strong>The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy.</strong>
|
|
Hum. Molec. Genet. 16: 2892-2899, 2007.
|
|
|
|
|
|
[PubMed: 17881658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm248]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meisler, M. H., Sprunger, L. K., Plummer, N. W., Escayg, A., Jones, J. M.
|
|
<strong>Ion channel mutations in mouse models of inherited neurological disease.</strong>
|
|
Ann. Med. 29: 569-574, 1997.
|
|
|
|
|
|
[PubMed: 9562526]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3109/07853899709007484]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ohba, C., Kato, M., Takahashi, S., Lerman-Sagie, T., Lev, D., Terashima, H., Kubota, M., Kawawaki, H., Matsufuji, M., Kojima, Y., Tateno, A., Goldberg-Stern, H., and 10 others.
|
|
<strong>Early onset epileptic encephalopathy caused by de novo SCN8A mutations.</strong>
|
|
Epilepsia 55: 994-1000, 2014.
|
|
|
|
|
|
[PubMed: 24888894]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/epi.12668]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Papale, L. A., Beyer, B., Jones, J. M., Sharkey, L. M., Tufik, S., Epstein, M., Letts, V. A., Meisler, M. H., Frankel, W. N., Escayg, A.
|
|
<strong>Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice.</strong>
|
|
Hum. Molec. Genet. 18: 1633-1641, 2009.
|
|
|
|
|
|
[PubMed: 19254928]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp081]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Plummer, N. W., Galt, J., Jones, J. M., Burgess, D. L., Sprunger, L. K., Kohrman, D. C., Meisler, M. H.
|
|
<strong>Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.</strong>
|
|
Genomics 54: 287-296, 1998.
|
|
|
|
|
|
[PubMed: 9828131]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1998.5550]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Plummer, N. W., McBurney, M. W., Meisler, M. H.
|
|
<strong>Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.</strong>
|
|
J. Biol. Chem. 272: 24008-24015, 1997.
|
|
|
|
|
|
[PubMed: 9295353]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.272.38.24008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sprunger, L. K., Escayg, A., Tallaksen-Greene, S., Albin, R. L., Meisler, M. H.
|
|
<strong>Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3.</strong>
|
|
Hum. Molec. Genet. 8: 471-479, 1999.
|
|
|
|
|
|
[PubMed: 9949206]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.3.471]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Trudeau, M. M., Dalton, J. C., Day, J. W., Ranum, L. P. W., Meisler, M. H.
|
|
<strong>Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. (Letter)</strong>
|
|
J. Med. Genet. 43: 527-530, 2006.
|
|
|
|
|
|
[PubMed: 16236810]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2005.035667]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Veeramah, K. R., O'Brien, J. E., Meisler, M. H., Cheng, X., Dib-Hajj, S. D., Waxman, S. G., Talwar, D., Girirajan, S., Eichler, E. E., Restifo, L. L., Erickson, R. P., Hammer, M. F.
|
|
<strong>De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.</strong>
|
|
Am. J. Hum. Genet. 90: 502-512, 2012.
|
|
|
|
|
|
[PubMed: 22365152]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.01.006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., Swinkels, M. E. M., Patel, M. K., Meisler, M. H.
|
|
<strong>Loss-of-function variants of SCN8A in intellectual disability without seizures.</strong>
|
|
Neurol. Genet. 3: e170, 2017. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 28702509]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/NXG.0000000000000170]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wagnon, J. L., Mencacci, N. E., Barker, B. S., Wengert, E. R., Bhatia, K. P., Balint, B., Carecchio, M., Wood, N. W., Patel, M. K., Meisler, M. H.
|
|
<strong>Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus.</strong>
|
|
Hum. Mutat. 39: 965-969, 2018.
|
|
|
|
|
|
[PubMed: 29726066]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.23547]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., Spain, W. J., McKnight, G. S., Scheuer, T., Catterall, W. A.
|
|
<strong>Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.</strong>
|
|
Nature Neurosci. 9: 1142-1149, 2006. Note: Erratum: Nature Neurosci. 10: 134 only, 2007.
|
|
|
|
|
|
[PubMed: 16921370]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn1754]
|
|
|
|
|
|
</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">
|
|
Alan F. Scott - updated : 07/29/2019<br>Cassandra L. Kniffin - updated : 03/25/2019<br>Cassandra L. Kniffin - updated : 03/21/2019<br>Cassandra L. Kniffin - updated : 08/18/2016<br>Cassandra L. Kniffin - updated : 6/8/2015<br>Cassandra L. Kniffin - updated : 12/9/2014<br>Cassandra L. Kniffin - updated : 9/22/2014<br>Cassandra L. Kniffin - updated : 8/15/2013<br>Cassandra L. Kniffin - updated : 3/28/2012<br>Cassandra L. Kniffin - updated : 10/31/2011<br>Ada Hamosh - updated : 5/27/2010<br>George E. Tiller - updated : 11/25/2009<br>Cassandra L. Kniffin - updated : 9/2/2009<br>Patricia A. Hartz - updated : 9/10/2008<br>Victor A. McKusick - updated : 7/5/2006<br>George E. Tiller - updated : 2/13/2004<br>George E. Tiller - updated : 2/5/2002<br>Carol A. Bocchini - updated : 5/30/2001<br>Michael J. Wright - updated : 2/5/2001<br>Victor A. McKusick - updated : 3/19/1999<br>Victor A. McKusick - updated : 11/30/1998<br>Victor A. McKusick - updated : 11/23/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 7/31/1995
|
|
</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 : 11/15/2024<br>ckniffin : 03/08/2023<br>carol : 01/18/2023<br>mgross : 01/17/2023<br>alopez : 12/03/2020<br>alopez : 10/19/2020<br>joanna : 10/09/2020<br>carol : 09/01/2020<br>alopez : 07/29/2019<br>carol : 03/29/2019<br>ckniffin : 03/25/2019<br>carol : 03/21/2019<br>ckniffin : 03/21/2019<br>carol : 02/28/2017<br>carol : 08/22/2016<br>ckniffin : 08/18/2016<br>carol : 11/25/2015<br>carol : 6/10/2015<br>mcolton : 6/9/2015<br>ckniffin : 6/8/2015<br>carol : 12/11/2014<br>mcolton : 12/10/2014<br>ckniffin : 12/9/2014<br>carol : 11/26/2014<br>carol : 9/22/2014<br>ckniffin : 9/22/2014<br>carol : 8/19/2013<br>ckniffin : 8/15/2013<br>carol : 5/29/2013<br>mgross : 4/13/2012<br>carol : 4/2/2012<br>ckniffin : 3/28/2012<br>carol : 10/31/2011<br>carol : 10/31/2011<br>ckniffin : 10/31/2011<br>joanna : 7/27/2010<br>carol : 6/11/2010<br>alopez : 6/1/2010<br>terry : 5/27/2010<br>wwang : 12/4/2009<br>terry : 11/25/2009<br>wwang : 9/10/2009<br>ckniffin : 9/2/2009<br>mgross : 9/10/2008<br>terry : 9/10/2008<br>carol : 10/4/2006<br>alopez : 7/10/2006<br>alopez : 7/10/2006<br>alopez : 7/7/2006<br>terry : 7/5/2006<br>cwells : 2/13/2004<br>cwells : 2/14/2002<br>cwells : 2/5/2002<br>cwells : 2/5/2002<br>carol : 6/14/2001<br>carol : 5/30/2001<br>alopez : 2/5/2001<br>kayiaros : 7/8/1999<br>carol : 7/7/1999<br>terry : 4/29/1999<br>mgross : 3/29/1999<br>mgross : 3/26/1999<br>terry : 3/19/1999<br>carol : 11/30/1998<br>carol : 11/23/1998<br>terry : 9/6/1995<br>mark : 7/31/1995
|
|
</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>
|
|
|
|
|