3192 lines
213 KiB
Text
3192 lines
213 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
|
|
|
|
- #158600 - SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 1, AUTOSOMAL DOMINANT; SMALED1
|
|
|
|
|
|
- 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=158600"><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">#158600</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="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/158600"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS158600"> <strong>Phenotypic Series</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="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</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="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 1, AUTOSOMAL DOMINANT" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
|
|
<div id="mimEuroGentestFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=18655&Typ=Pat" title="DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">DYNC1H1-related autosomal … </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=22306&Typ=Pat" title="Autosomal dominant childhood-onset proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Autosomal dominant childho… </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK601997/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/9336" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=158600[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
|
|
<div id="mimOrphanetFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=209341" title="DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">DYNC1H1-related autosomal …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363447" title="Autosomal dominant childhood-onset proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Autosomal dominant childho…</a></div>
|
|
</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/disease/DOID:0070351" 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="http://www.informatics.jax.org/disease/158600" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0070351" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</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> 772129007<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 209341, 363447<br />
|
|
|
|
|
|
<strong>DO:</strong> 0070351<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
158600
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 1, AUTOSOMAL DOMINANT; SMALED1
|
|
|
|
</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">
|
|
SMALED<br />
|
|
SPINAL MUSCULAR ATROPHY, CHILDHOOD, PROXIMAL, AUTOSOMAL DOMINANT<br />
|
|
SPINAL MUSCULAR ATROPHY, JUVENILE, PROXIMAL, AUTOSOMAL DOMINANT<br />
|
|
KUGELBERG-WELANDER SYNDROME, AUTOSOMAL DOMINANT
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/559?start=-3&limit=10&highlight=559">
|
|
14q32.31
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Spinal muscular atrophy, lower extremity-predominant 1, AD
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/158600"> 158600 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
DYNC1H1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600112"> 600112 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/158600" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS158600" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</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/158600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/158600" 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>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Feet </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Foot deformities (variable) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805751&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805751</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229844004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229844004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001760" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001760</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Muscle weakness, symmetric, proximal, lower limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805750&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805750</a>]</span><br /> -
|
|
Muscle atrophy, lower limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843318&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843318</a>]</span><br /> -
|
|
Hip abductor weakness and atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277186&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277186</a>]</span><br /> -
|
|
Type 2 muscle fiber predominance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277187&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277187</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010602" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010602</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010602" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010602</a>]</span><br /> -
|
|
EMG shows chronic denervation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864699&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864699</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Delayed walking <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241726&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241726</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031936</a>]</span><br /> -
|
|
Difficulty running and climbing stairs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277182&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277182</a>]</span><br /> -
|
|
Muscle weakness, symmetric, proximal due to motor neuronopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277183&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277183</a>]</span><br /> -
|
|
Waddling gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271706000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271706000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231712&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231712</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002515" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002515</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002515" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002515</a>]</span><br /> -
|
|
Cognitive delay, mild (1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549880&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549880</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Decreased patellar reflexes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277184&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277184</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011808</a>]</span><br /> -
|
|
No sensory impairment <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549881&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549881</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset in early childhood<br /> -
|
|
Non-progressive or very slowly progressive<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the dynein, cytoplasmic 1, heavy chain 1 gene (DYNC1H1, <a href="/entry/600112#0001">600112.0001</a>).<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Spinal muscular atrophy, lower extremity-predominant
|
|
- <a href="/phenotypicSeries/PS158600">PS158600</a>
|
|
- 3 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/310?start=-3&limit=10&highlight=310"> 9q22.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618291"> Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618291"> 618291 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609797"> BICD2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609797"> 609797 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/310?start=-3&limit=10&highlight=310"> 9q22.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615290"> Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615290"> 615290 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609797"> BICD2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609797"> 609797 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/559?start=-3&limit=10&highlight=559"> 14q32.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/158600"> Spinal muscular atrophy, lower extremity-predominant 1, AD </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/158600"> 158600 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600112"> DYNC1H1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600112"> 600112 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because autosomal dominant lower extremity-predominant spinal muscular atrophy-1 (SMALED1) is caused by heterozygous mutation in the DYNC1H1 gene (<a href="/entry/600112">600112</a>) on chromosome 14q32.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<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>Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. SMALED shows autosomal dominant inheritance with muscle weakness predominantly affecting the proximal lower extremities (<a href="#5" class="mim-tip-reference" title="Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H. <strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong> Neurology 75: 539-546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697106</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20697106[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/WNL.0b013e3181ec800c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20697106">Harms et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20697106" 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 most common form of SMA (see, e.g., SMA1, <a href="/entry/253300">253300</a>) shows autosomal recessive inheritance and is due to mutation in the SMN1 gene (<a href="/entry/600354">600354</a>) on chromosome 5q.</p><p><strong><em>Genetic Heterogeneity of Lower Extremity-Predominant Spinal Muscular Atrophy</em></strong></p><p>
|
|
See also SMALED2A (<a href="/entry/615290">615290</a>) and SMALED2B (<a href="/entry/618291">618291</a>), both of which are caused by mutation in the BICD2 gene (<a href="/entry/609797">609797</a>) on chromosome 9q22. SMALED2A and SMALED2B differ in age at onset and severity, with SMALED2B being more severe.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#13" class="mim-tip-reference" title="Timme, W. <strong>Progressive muscular dystrophy as an endocrine disease.</strong> Arch. Intern. Med. 19: 79-104, 1917."None>Timme (1917)</a> described a family with a dominant form of proximal 'muscular dystrophy' with onset at age 3 or 4 years, but with little if any effect on longevity and useful life. Gowers sign was noted early and the difficulty in getting up from the floor increased with age. Some affected individuals required lengthening of the Achilles tendon. <a href="#19" class="mim-tip-reference" title="Young, P. T. <strong>Personal Communication.</strong> Claremont, Calif. 1972."None>Young (1972)</a> provided follow-up of this family, which included 13 affected persons spanning 4 generations. The clinical picture was most consistent with an autosomal dominant childhood-onset spinal muscular atrophy. There were no additional features.</p><p><a href="#12" class="mim-tip-reference" title="Saul, R. A., Meyer, L. C. <strong>Autosomal dominant spinal muscular atrophy in three generations.</strong> Proc. Greenwood Genet. Center 4: 13-15, 1985."None>Saul and Meyer (1985)</a> reported a family with 5 affected persons in 3 generations.</p><p><a href="#5" class="mim-tip-reference" title="Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H. <strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong> Neurology 75: 539-546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697106</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20697106[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/WNL.0b013e3181ec800c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20697106">Harms et al. (2010)</a> reported a large 6-generation North American family with early-onset spinal muscular atrophy affecting the proximal lower extremities. The disorder was manifest by prominent weakness and atrophy of the quadriceps muscles, moderate to severe atrophy of the hip abductors, and milder weakness in other leg muscles. Upper extremity strength and sensation were normal. Ten affected individuals were studied. Most patients had onset of symptoms in the first 2 years of life, although 3 had onset between 4 and 7 years of age. The disorder was static or only mildly progressive. None had arthrogryposis or contractures, but 5 had mild pes cavus. The 53-year-old proband reportedly had underdeveloped leg muscles in infancy, delayed motor development, and a lifelong history of difficulty running and climbing stairs. Examination at age 49 showed neurogenic weakness and atrophy of the lower limbs, most prominent in the quadriceps. There was also mild atrophy of distal leg muscles. Other muscles, including knee flexors, distal leg, face, neck, and upper extremity muscles showed normal strength. He had a waddling gait with excessive lumbar lordosis. No fasciculations were observed. This patient also showed mild, subclinical, chronic denervation in the hand, but his affected child did not, suggesting either that upper limb involvement may be related to length of disease or that there is intrafamilial variability. Other affected family members had a similar phenotype; none had arm or neck weakness, and all remained ambulatory into the sixth decade. Electromyographic (EMG) studies and skeletal muscle biopsies on 2 patients indicated chronic denervation. There was type II muscle fiber predominance, suggesting successive rounds of denervation and reinnervation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20697106" 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="Harms, M. B., Ori-McKenney, K. M., Scoto, M., Tuck, E. P., Bell, S., Ma, D., Masi, S., Allred, P., Al-Lozi, M., Reilly, M. M., Miller, L. J., Jani-Acsadi, A., Pestronk, A., Shy, M. E., Muntoni, F., Vallee, R. B., Baloh, R. H. <strong>Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.</strong> Neurology 78: 1714-1720, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22459677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22459677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22459677[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/WNL.0b013e3182556c05" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22459677">Harms et al. (2012)</a> reported a 3-generation family with SMALED confirmed by genetic analysis. The 3 affected individuals showed waddling gait from early childhood, with awkward running due to lower limb weakness; upper limbs were unaffected. Muscle atrophy and weakness confined to the lower limbs showed little progression throughout life. There was a notable strength discrepancy between knee extension and flexion, with the quadriceps showing significant weakness. Deep tendon reflexes were reduced at the knees, but normal elsewhere. Nerve conduction studies showed small motor responses and normal sensory responses; EMG showed chronic denervation. One patient had heel cord contractures and in-turning feet, whereas another had fasciculations of the calves. Another unrelated girl with the disorder showed delayed motor development, calcaneovalgus foot deformities, lower extremity weakness, and mild cognitive delay. At age 3.5 years, she could not run and had an unsteady gait. There was no sensory loss. EMG was consistent with nonlength-dependent motor neuron disease. A sister, who was not studied, reportedly had similar motor delay diagnosed as cerebral palsy, abnormal gait, and polymicrogyria on brain imaging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22459677" 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="Tsurusaki, Y., Saitoh, S., Tomizawa, K., Sudo, A., Asahina, N., Shiraishi, H., Ito, J., Tanaka, H., Doi, H., Saitsu, H., Miyake, N., Matsumoto, N. <strong>A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance.</strong> Neurogenetics 13: 327-332, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22847149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22847149</a>] [<a href="https://doi.org/10.1007/s10048-012-0337-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22847149">Tsurusaki et al. (2012)</a> reported a Japanese mother and her 2 children with autosomal dominant spinal muscular atrophy with lower extremity predominance. Both children showed mildly delayed walking followed by persistently unstable gait due to muscle weakness in the proximal lower limbs. Imaging showed atrophy and lipid degeneration of the quadriceps femoris muscle. Muscle biopsy of 1 patient showed severe grouping atrophy of type 2 fibers, sparse enlarged type 1 fibers, and increased fibrous tissue. EMG of the other patient indicated a neurogenic pattern. The mother was only ascertained as being affected after her children were examined. The mother did not have a waddling gait, but had difficulty squatting and mild muscle atrophy in the hip. Imaging showed quadriceps-dominant muscle atrophy and lipid degeneration. None of the patients had upper limb involvement, and sensation and intellectual function were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22847149" 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="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Tsukagoshi, H., Sugita, H., Furukawa, T., Tsubaki, T., Ono, E. <strong>Kugelberg-Welander syndrome with dominant inheritance.</strong> Arch. Neurol. 14: 378-381, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5906462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5906462</a>] [<a href="https://doi.org/10.1001/archneur.1966.00470100034004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5906462">Tsukagoshi et al. (1966)</a> reported autosomal dominant inheritance of the disorder, but quasidominance due to consanguinity may have been possible in at least 1 family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5906462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Garvie, J. M., Woolf, A. L. <strong>Kugelberg-Welander syndrome (hereditary proximal spinal muscular atrophy).</strong> Brit. Med. J. 1: 1458-1461, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5933049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5933049</a>] [<a href="https://doi.org/10.1136/bmj.1.5501.1458" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5933049">Garvie and Woolf (1966)</a> and <a href="#8" class="mim-tip-reference" title="Magee, K. R., DeJong, R. N. <strong>Neurogenic muscular atrophy simulating muscular dystrophy.</strong> Arch. Neurol. 2: 677-682, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14419782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14419782</a>] [<a href="https://doi.org/10.1001/archneur.1960.03840120083009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14419782">Magee and DeJong (1960)</a>, among others, also described autosomal dominant transmission of proximal spinal muscular atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14419782+5933049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Pearn, J. <strong>Autosomal dominant spinal muscular atrophy: a clinical and genetic study.</strong> J. Neurol. Sci. 38: 263-275, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/712386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">712386</a>] [<a href="https://doi.org/10.1016/0022-510x(78)90072-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="712386">Pearn (1978)</a> estimated that autosomal dominant SMA with childhood onset accounts for less than 2% of all childhood onset SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=712386" 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="Hausmanowa-Petrusewicz, I., Zaremba, J., Borkowska, J. <strong>Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling.</strong> J. Med. Genet. 22: 350-353, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2370051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2370051</a>] [<a href="https://doi.org/10.1007/BF00193198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2370051">Hausmanowa-Petrusewicz et al. (1985)</a> noted that proximal spinal muscular atrophy of childhood and adolescence is a heterogeneous condition, and suggested that some cases may be due to new dominant mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2370051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Wirth, B., Zerres, K. <strong>Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy.</strong> Am. J. Hum. Genet. 55: 112-119, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8023839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8023839</a>]" pmid="8023839">Rudnik-Schoneborn et al. (1994)</a> presented 3 pieces of evidence for the existence of an autosomal dominant form of childhood-onset proximal spinal muscular atrophy distinct from the more common forms of autosomal recessive SMA (<a href="/entry/253300">253300</a>). First, segregation analysis performed in 333 families with proximal SMA affecting only individuals in 1 generation showed a deviation from autosomal recessive inheritance. Second, they reported 3 pedigrees with proximal SMA in 2 generations with the disorder apparently starting as a de novo mutation in the affected parent. Third, they reported data on 5 of 93 informative SMA families who did not show linkage with 5q markers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8023839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By genomewide linkage analysis of a North American family with autosomal dominant spinal muscular atrophy affecting the lower limbs, <a href="#5" class="mim-tip-reference" title="Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H. <strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong> Neurology 75: 539-546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697106</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20697106[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/WNL.0b013e3181ec800c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20697106">Harms et al. (2010)</a> found significant linkage to chromosome 14q32 (maximum 2-point lod score of 5.10 at <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs17679127;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs17679127</a>). Linkage to 14q32 was further supported by multipoint parametric lod scores of 3.00 between <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2615453;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2615453</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10143250;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10143250</a>. Haplotype analysis identified a 6.1-Mb disease-associated interval, containing 73 known or predicted genes.. <a href="#5" class="mim-tip-reference" title="Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H. <strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong> Neurology 75: 539-546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697106</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20697106[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/WNL.0b013e3181ec800c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20697106">Harms et al. (2010)</a> proposed the designation spinal muscular atrophy-lower extremity, dominant (SMALED) for this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20697106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large family with autosomal dominant lower extremity spinal muscular atrophy originally reported by <a href="#5" class="mim-tip-reference" title="Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H. <strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong> Neurology 75: 539-546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697106</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20697106[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/WNL.0b013e3181ec800c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20697106">Harms et al. (2010)</a>, <a href="#6" class="mim-tip-reference" title="Harms, M. B., Ori-McKenney, K. M., Scoto, M., Tuck, E. P., Bell, S., Ma, D., Masi, S., Allred, P., Al-Lozi, M., Reilly, M. M., Miller, L. J., Jani-Acsadi, A., Pestronk, A., Shy, M. E., Muntoni, F., Vallee, R. B., Baloh, R. H. <strong>Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.</strong> Neurology 78: 1714-1720, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22459677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22459677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22459677[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/WNL.0b013e3182556c05" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22459677">Harms et al. (2012)</a> identified a heterozygous 1750A-C mutation in the DYNC1H1 gene (I584L; <a href="/entry/600112#0004">600112.0004</a>). The mutation was identified by sequencing all exons of 73 annotated genes in the 14q32 linkage interval using custom target capture followed by next-generation sequencing. Patient skin fibroblasts showed normal binding to microtubules in the absence of ATP, but markedly decreased binding to microtubules in the presence of ATP. The mutant dynein also appeared to disrupt the stability of the dynein complex. Sequencing of this gene in 32 additional probands with a similar disorder identified 2 additional families with a heterozygous DYNC1H1 mutation (<a href="/entry/600112#0005">600112.0005</a> and <a href="/entry/600112#0006">600112.0006</a>). The findings were similar to those observed in Loa homozygous mice, who have a mutation in the Dync1h1 gene (<a href="#4" class="mim-tip-reference" title="Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A. S., Hummerich, H., Nicholson, S., Morgan, P. J., Oozageer, R., and 27 others. <strong>Mutations in dynein link motor neuron degeneration to defects in retrograde transport.</strong> Science 300: 808-812, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730604</a>] [<a href="https://doi.org/10.1126/science.1083129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12730604">Hafezparast et al., 2003</a>; <a href="#9" class="mim-tip-reference" title="Ori-McKenney, K. M., Xu, J., Gross, S. P., Vallee, R. B. <strong>A cytoplasmic dynein tail mutation impairs motor processivity.</strong> Nature Cell Biol. 12: 1228-1234, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21102439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21102439</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21102439[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/ncb2127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21102439">Ori-McKenney et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12730604+21102439+22459677+20697106" 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 Japanese sibs with autosomal dominant lower extremity spinal muscular atrophy and no sensory symptoms, <a href="#15" class="mim-tip-reference" title="Tsurusaki, Y., Saitoh, S., Tomizawa, K., Sudo, A., Asahina, N., Shiraishi, H., Ito, J., Tanaka, H., Doi, H., Saitsu, H., Miyake, N., Matsumoto, N. <strong>A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance.</strong> Neurogenetics 13: 327-332, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22847149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22847149</a>] [<a href="https://doi.org/10.1007/s10048-012-0337-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22847149">Tsurusaki et al. (2012)</a> identified a heterozygous missense mutation in the DYNC1H1 gene (H306R; <a href="/entry/600112#0001">600112.0001</a>). The mutation, which was found by exome sequencing, was inherited from their mother, who had mild symptoms. The same mutation had previously been found by <a href="#16" class="mim-tip-reference" title="Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T., Williams, M., King, C., Greenhalgh, L., Newbury-Ecob, R., Ellard, S. <strong>Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 89: 308-312, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820100</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820100[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.2011.07.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820100">Weedon et al. (2011)</a> in a family with autosomal dominant axonal Charcot-Marie-Tooth disease type 2O (CMT2O; <a href="/entry/614228">614228</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22847149+21820100" 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="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Young, P. T. <strong>Personal Communication.</strong> Claremont, Calif. 1972."None>Young (1972)</a> provided follow-up of the family reported by <a href="#13" class="mim-tip-reference" title="Timme, W. <strong>Progressive muscular dystrophy as an endocrine disease.</strong> Arch. Intern. Med. 19: 79-104, 1917."None>Timme (1917)</a>, noting that the disorder did not prevent productive life, as indicated by the biography of one of the affected persons (<a href="#17" class="mim-tip-reference" title="Young, N. M. <strong>William Stewart Young, Builder of California Institutions.</strong> Glendale, Calif.: Arthur H. Clark Co. (pub.) 1967."None>Young, 1967</a>), William Stewart Young, a cofounder of Occidental College. An autopsy report by <a href="#2" class="mim-tip-reference" title="Butt, E. M., Hall, E. M., Courville, C. B. <strong>Progressive muscular dystrophy (dystrophia myotonica).</strong> Bull. Los Angeles Neurol. Soc. 4: 58-68, 1939."None>Butt et al. (1939)</a>, who wrongly labeled the disorder as dystrophia myotonica (<a href="/entry/160900">160900</a>), a distal myopathy, also noted that affected persons could maintain a productive life. There were no additional features, such as cataract, myotonia, diabetes, or mental retardation in the family. One of the affected members of the family, son of William Stewart Young, gave a useful description of mechanical aids for patients with muscular disability (<a href="#18" class="mim-tip-reference" title="Young, P. T. <strong>Mechanical aids for patients with muscular disability.</strong> J. Bone Joint Surg. Am. 31: 428-430, 1949."None>Young, 1949</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Baraitser1982" class="mim-tip-reference" title="Baraitser, M. <strong>The Genetics of Neurological Disorders.</strong> Oxford: Oxford Univ. Press (pub.) 1982.">Baraitser (1982)</a>; <a href="#Zellweger1972" class="mim-tip-reference" title="Zellweger, H., Simpson, J., McCormick, W. F., Ionasescu, V. <strong>Spinal muscular atrophy with autosomal dominant inheritance: report of a new kindred.</strong> Neurology 22: 957-963, 1972.">Zellweger et al. (1972)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Baraitser1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Baraitser, M.
|
|
<strong>The Genetics of Neurological Disorders.</strong>
|
|
Oxford: Oxford Univ. Press (pub.) 1982.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Butt1939" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Butt, E. M., Hall, E. M., Courville, C. B.
|
|
<strong>Progressive muscular dystrophy (dystrophia myotonica).</strong>
|
|
Bull. Los Angeles Neurol. Soc. 4: 58-68, 1939.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Garvie1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garvie, J. M., Woolf, A. L.
|
|
<strong>Kugelberg-Welander syndrome (hereditary proximal spinal muscular atrophy).</strong>
|
|
Brit. Med. J. 1: 1458-1461, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5933049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5933049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5933049" 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/bmj.1.5501.1458" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Hafezparast2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A. S., Hummerich, H., Nicholson, S., Morgan, P. J., Oozageer, R., and 27 others.
|
|
<strong>Mutations in dynein link motor neuron degeneration to defects in retrograde transport.</strong>
|
|
Science 300: 808-812, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730604" 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.1083129" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Harms2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H.
|
|
<strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong>
|
|
Neurology 75: 539-546, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697106</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20697106[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=20697106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0b013e3181ec800c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Harms2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harms, M. B., Ori-McKenney, K. M., Scoto, M., Tuck, E. P., Bell, S., Ma, D., Masi, S., Allred, P., Al-Lozi, M., Reilly, M. M., Miller, L. J., Jani-Acsadi, A., Pestronk, A., Shy, M. E., Muntoni, F., Vallee, R. B., Baloh, R. H.
|
|
<strong>Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.</strong>
|
|
Neurology 78: 1714-1720, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22459677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22459677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22459677[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=22459677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0b013e3182556c05" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Hausmanowa-Petrusewicz1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hausmanowa-Petrusewicz, I., Zaremba, J., Borkowska, J.
|
|
<strong>Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling.</strong>
|
|
J. Med. Genet. 22: 350-353, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2370051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2370051</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2370051" 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/BF00193198" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Magee1960" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Magee, K. R., DeJong, R. N.
|
|
<strong>Neurogenic muscular atrophy simulating muscular dystrophy.</strong>
|
|
Arch. Neurol. 2: 677-682, 1960.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14419782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14419782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14419782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1960.03840120083009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Ori-McKenney2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ori-McKenney, K. M., Xu, J., Gross, S. P., Vallee, R. B.
|
|
<strong>A cytoplasmic dynein tail mutation impairs motor processivity.</strong>
|
|
Nature Cell Biol. 12: 1228-1234, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21102439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21102439</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21102439[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=21102439" 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/ncb2127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Pearn1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pearn, J.
|
|
<strong>Autosomal dominant spinal muscular atrophy: a clinical and genetic study.</strong>
|
|
J. Neurol. Sci. 38: 263-275, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/712386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">712386</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=712386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0022-510x(78)90072-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Rudnik-Schoneborn1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Wirth, B., Zerres, K.
|
|
<strong>Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy.</strong>
|
|
Am. J. Hum. Genet. 55: 112-119, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8023839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8023839</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8023839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Saul1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saul, R. A., Meyer, L. C.
|
|
<strong>Autosomal dominant spinal muscular atrophy in three generations.</strong>
|
|
Proc. Greenwood Genet. Center 4: 13-15, 1985.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Timme1917" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Timme, W.
|
|
<strong>Progressive muscular dystrophy as an endocrine disease.</strong>
|
|
Arch. Intern. Med. 19: 79-104, 1917.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Tsukagoshi1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsukagoshi, H., Sugita, H., Furukawa, T., Tsubaki, T., Ono, E.
|
|
<strong>Kugelberg-Welander syndrome with dominant inheritance.</strong>
|
|
Arch. Neurol. 14: 378-381, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5906462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5906462</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5906462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1966.00470100034004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Tsurusaki2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsurusaki, Y., Saitoh, S., Tomizawa, K., Sudo, A., Asahina, N., Shiraishi, H., Ito, J., Tanaka, H., Doi, H., Saitsu, H., Miyake, N., Matsumoto, N.
|
|
<strong>A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance.</strong>
|
|
Neurogenetics 13: 327-332, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22847149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22847149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22847149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10048-012-0337-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Weedon2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T., Williams, M., King, C., Greenhalgh, L., Newbury-Ecob, R., Ellard, S.
|
|
<strong>Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease.</strong>
|
|
Am. J. Hum. Genet. 89: 308-312, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820100</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820100[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=21820100" 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.2011.07.002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Young1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Young, N. M.
|
|
<strong>William Stewart Young, Builder of California Institutions.</strong>
|
|
Glendale, Calif.: Arthur H. Clark Co. (pub.) 1967.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Young1949" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Young, P. T.
|
|
<strong>Mechanical aids for patients with muscular disability.</strong>
|
|
J. Bone Joint Surg. Am. 31: 428-430, 1949.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Young1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Young, P. T.
|
|
<strong>Personal Communication.</strong>
|
|
Claremont, Calif. 1972.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Zellweger1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zellweger, H., Simpson, J., McCormick, W. F., Ionasescu, V.
|
|
<strong>Spinal muscular atrophy with autosomal dominant inheritance: report of a new kindred.</strong>
|
|
Neurology 22: 957-963, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4673381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4673381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4673381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.22.9.957" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 9/23/2013
|
|
</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 : 6/27/2013<br>Cassandra L. Kniffin - updated : 4/25/2012<br>Cassandra L. Kniffin - updated : 10/20/2010
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/2/1986
|
|
</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">
|
|
carol : 01/29/2019
|
|
</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 : 01/23/2019<br>carol : 03/25/2016<br>ckniffin : 3/11/2016<br>carol : 5/1/2014<br>tpirozzi : 9/26/2013<br>ckniffin : 9/23/2013<br>carol : 7/10/2013<br>carol : 7/9/2013<br>ckniffin : 6/27/2013<br>terry : 7/5/2012<br>terry : 5/2/2012<br>carol : 4/27/2012<br>ckniffin : 4/25/2012<br>terry : 1/13/2011<br>wwang : 11/1/2010<br>ckniffin : 10/20/2010<br>alopez : 5/31/2007<br>alopez : 5/31/2007<br>carol : 3/31/2004<br>ckniffin : 3/29/2004<br>ckniffin : 3/29/2004<br>mgross : 3/17/2004<br>mimadm : 11/6/1994<br>supermim : 3/16/1992<br>carol : 11/30/1990<br>carol : 11/21/1990<br>supermim : 3/20/1990<br>ddp : 10/27/1989
|
|
</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> 158600
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 1, AUTOSOMAL DOMINANT; SMALED1
|
|
|
|
</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">
|
|
SMALED<br />
|
|
SPINAL MUSCULAR ATROPHY, CHILDHOOD, PROXIMAL, AUTOSOMAL DOMINANT<br />
|
|
SPINAL MUSCULAR ATROPHY, JUVENILE, PROXIMAL, AUTOSOMAL DOMINANT<br />
|
|
KUGELBERG-WELANDER SYNDROME, AUTOSOMAL DOMINANT
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 772129007;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 209341, 363447;
|
|
|
|
|
|
<strong>DO:</strong> 0070351;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene 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>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
14q32.31
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Spinal muscular atrophy, lower extremity-predominant 1, AD
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
158600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
DYNC1H1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600112
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because autosomal dominant lower extremity-predominant spinal muscular atrophy-1 (SMALED1) is caused by heterozygous mutation in the DYNC1H1 gene (600112) on chromosome 14q32.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. SMALED shows autosomal dominant inheritance with muscle weakness predominantly affecting the proximal lower extremities (Harms et al., 2010). </p><p>The most common form of SMA (see, e.g., SMA1, 253300) shows autosomal recessive inheritance and is due to mutation in the SMN1 gene (600354) on chromosome 5q.</p><p><strong><em>Genetic Heterogeneity of Lower Extremity-Predominant Spinal Muscular Atrophy</em></strong></p><p>
|
|
See also SMALED2A (615290) and SMALED2B (618291), both of which are caused by mutation in the BICD2 gene (609797) on chromosome 9q22. SMALED2A and SMALED2B differ in age at onset and severity, with SMALED2B being more severe.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Timme (1917) described a family with a dominant form of proximal 'muscular dystrophy' with onset at age 3 or 4 years, but with little if any effect on longevity and useful life. Gowers sign was noted early and the difficulty in getting up from the floor increased with age. Some affected individuals required lengthening of the Achilles tendon. Young (1972) provided follow-up of this family, which included 13 affected persons spanning 4 generations. The clinical picture was most consistent with an autosomal dominant childhood-onset spinal muscular atrophy. There were no additional features.</p><p>Saul and Meyer (1985) reported a family with 5 affected persons in 3 generations.</p><p>Harms et al. (2010) reported a large 6-generation North American family with early-onset spinal muscular atrophy affecting the proximal lower extremities. The disorder was manifest by prominent weakness and atrophy of the quadriceps muscles, moderate to severe atrophy of the hip abductors, and milder weakness in other leg muscles. Upper extremity strength and sensation were normal. Ten affected individuals were studied. Most patients had onset of symptoms in the first 2 years of life, although 3 had onset between 4 and 7 years of age. The disorder was static or only mildly progressive. None had arthrogryposis or contractures, but 5 had mild pes cavus. The 53-year-old proband reportedly had underdeveloped leg muscles in infancy, delayed motor development, and a lifelong history of difficulty running and climbing stairs. Examination at age 49 showed neurogenic weakness and atrophy of the lower limbs, most prominent in the quadriceps. There was also mild atrophy of distal leg muscles. Other muscles, including knee flexors, distal leg, face, neck, and upper extremity muscles showed normal strength. He had a waddling gait with excessive lumbar lordosis. No fasciculations were observed. This patient also showed mild, subclinical, chronic denervation in the hand, but his affected child did not, suggesting either that upper limb involvement may be related to length of disease or that there is intrafamilial variability. Other affected family members had a similar phenotype; none had arm or neck weakness, and all remained ambulatory into the sixth decade. Electromyographic (EMG) studies and skeletal muscle biopsies on 2 patients indicated chronic denervation. There was type II muscle fiber predominance, suggesting successive rounds of denervation and reinnervation. </p><p>Harms et al. (2012) reported a 3-generation family with SMALED confirmed by genetic analysis. The 3 affected individuals showed waddling gait from early childhood, with awkward running due to lower limb weakness; upper limbs were unaffected. Muscle atrophy and weakness confined to the lower limbs showed little progression throughout life. There was a notable strength discrepancy between knee extension and flexion, with the quadriceps showing significant weakness. Deep tendon reflexes were reduced at the knees, but normal elsewhere. Nerve conduction studies showed small motor responses and normal sensory responses; EMG showed chronic denervation. One patient had heel cord contractures and in-turning feet, whereas another had fasciculations of the calves. Another unrelated girl with the disorder showed delayed motor development, calcaneovalgus foot deformities, lower extremity weakness, and mild cognitive delay. At age 3.5 years, she could not run and had an unsteady gait. There was no sensory loss. EMG was consistent with nonlength-dependent motor neuron disease. A sister, who was not studied, reportedly had similar motor delay diagnosed as cerebral palsy, abnormal gait, and polymicrogyria on brain imaging. </p><p>Tsurusaki et al. (2012) reported a Japanese mother and her 2 children with autosomal dominant spinal muscular atrophy with lower extremity predominance. Both children showed mildly delayed walking followed by persistently unstable gait due to muscle weakness in the proximal lower limbs. Imaging showed atrophy and lipid degeneration of the quadriceps femoris muscle. Muscle biopsy of 1 patient showed severe grouping atrophy of type 2 fibers, sparse enlarged type 1 fibers, and increased fibrous tissue. EMG of the other patient indicated a neurogenic pattern. The mother was only ascertained as being affected after her children were examined. The mother did not have a waddling gait, but had difficulty squatting and mild muscle atrophy in the hip. Imaging showed quadriceps-dominant muscle atrophy and lipid degeneration. None of the patients had upper limb involvement, and sensation and intellectual function were normal. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Tsukagoshi et al. (1966) reported autosomal dominant inheritance of the disorder, but quasidominance due to consanguinity may have been possible in at least 1 family. </p><p>Garvie and Woolf (1966) and Magee and DeJong (1960), among others, also described autosomal dominant transmission of proximal spinal muscular atrophy. </p><p>Pearn (1978) estimated that autosomal dominant SMA with childhood onset accounts for less than 2% of all childhood onset SMA. </p><p>Hausmanowa-Petrusewicz et al. (1985) noted that proximal spinal muscular atrophy of childhood and adolescence is a heterogeneous condition, and suggested that some cases may be due to new dominant mutations. </p><p>Rudnik-Schoneborn et al. (1994) presented 3 pieces of evidence for the existence of an autosomal dominant form of childhood-onset proximal spinal muscular atrophy distinct from the more common forms of autosomal recessive SMA (253300). First, segregation analysis performed in 333 families with proximal SMA affecting only individuals in 1 generation showed a deviation from autosomal recessive inheritance. Second, they reported 3 pedigrees with proximal SMA in 2 generations with the disorder apparently starting as a de novo mutation in the affected parent. Third, they reported data on 5 of 93 informative SMA families who did not show linkage with 5q markers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomewide linkage analysis of a North American family with autosomal dominant spinal muscular atrophy affecting the lower limbs, Harms et al. (2010) found significant linkage to chromosome 14q32 (maximum 2-point lod score of 5.10 at rs17679127). Linkage to 14q32 was further supported by multipoint parametric lod scores of 3.00 between rs2615453 and rs10143250. Haplotype analysis identified a 6.1-Mb disease-associated interval, containing 73 known or predicted genes.. Harms et al. (2010) proposed the designation spinal muscular atrophy-lower extremity, dominant (SMALED) for this disorder. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large family with autosomal dominant lower extremity spinal muscular atrophy originally reported by Harms et al. (2010), Harms et al. (2012) identified a heterozygous 1750A-C mutation in the DYNC1H1 gene (I584L; 600112.0004). The mutation was identified by sequencing all exons of 73 annotated genes in the 14q32 linkage interval using custom target capture followed by next-generation sequencing. Patient skin fibroblasts showed normal binding to microtubules in the absence of ATP, but markedly decreased binding to microtubules in the presence of ATP. The mutant dynein also appeared to disrupt the stability of the dynein complex. Sequencing of this gene in 32 additional probands with a similar disorder identified 2 additional families with a heterozygous DYNC1H1 mutation (600112.0005 and 600112.0006). The findings were similar to those observed in Loa homozygous mice, who have a mutation in the Dync1h1 gene (Hafezparast et al., 2003; Ori-McKenney et al., 2010). </p><p>In 2 Japanese sibs with autosomal dominant lower extremity spinal muscular atrophy and no sensory symptoms, Tsurusaki et al. (2012) identified a heterozygous missense mutation in the DYNC1H1 gene (H306R; 600112.0001). The mutation, which was found by exome sequencing, was inherited from their mother, who had mild symptoms. The same mutation had previously been found by Weedon et al. (2011) in a family with autosomal dominant axonal Charcot-Marie-Tooth disease type 2O (CMT2O; 614228). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Young (1972) provided follow-up of the family reported by Timme (1917), noting that the disorder did not prevent productive life, as indicated by the biography of one of the affected persons (Young, 1967), William Stewart Young, a cofounder of Occidental College. An autopsy report by Butt et al. (1939), who wrongly labeled the disorder as dystrophia myotonica (160900), a distal myopathy, also noted that affected persons could maintain a productive life. There were no additional features, such as cataract, myotonia, diabetes, or mental retardation in the family. One of the affected members of the family, son of William Stewart Young, gave a useful description of mechanical aids for patients with muscular disability (Young, 1949).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Baraitser (1982); Zellweger et al. (1972)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baraitser, M.
|
|
<strong>The Genetics of Neurological Disorders.</strong>
|
|
Oxford: Oxford Univ. Press (pub.) 1982.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Butt, E. M., Hall, E. M., Courville, C. B.
|
|
<strong>Progressive muscular dystrophy (dystrophia myotonica).</strong>
|
|
Bull. Los Angeles Neurol. Soc. 4: 58-68, 1939.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garvie, J. M., Woolf, A. L.
|
|
<strong>Kugelberg-Welander syndrome (hereditary proximal spinal muscular atrophy).</strong>
|
|
Brit. Med. J. 1: 1458-1461, 1966.
|
|
|
|
|
|
[PubMed: 5933049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.1.5501.1458]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A. S., Hummerich, H., Nicholson, S., Morgan, P. J., Oozageer, R., and 27 others.
|
|
<strong>Mutations in dynein link motor neuron degeneration to defects in retrograde transport.</strong>
|
|
Science 300: 808-812, 2003.
|
|
|
|
|
|
[PubMed: 12730604]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1083129]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H.
|
|
<strong>Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.</strong>
|
|
Neurology 75: 539-546, 2010.
|
|
|
|
|
|
[PubMed: 20697106]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e3181ec800c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harms, M. B., Ori-McKenney, K. M., Scoto, M., Tuck, E. P., Bell, S., Ma, D., Masi, S., Allred, P., Al-Lozi, M., Reilly, M. M., Miller, L. J., Jani-Acsadi, A., Pestronk, A., Shy, M. E., Muntoni, F., Vallee, R. B., Baloh, R. H.
|
|
<strong>Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.</strong>
|
|
Neurology 78: 1714-1720, 2012.
|
|
|
|
|
|
[PubMed: 22459677]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e3182556c05]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hausmanowa-Petrusewicz, I., Zaremba, J., Borkowska, J.
|
|
<strong>Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling.</strong>
|
|
J. Med. Genet. 22: 350-353, 1985.
|
|
|
|
|
|
[PubMed: 2370051]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00193198]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Magee, K. R., DeJong, R. N.
|
|
<strong>Neurogenic muscular atrophy simulating muscular dystrophy.</strong>
|
|
Arch. Neurol. 2: 677-682, 1960.
|
|
|
|
|
|
[PubMed: 14419782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1960.03840120083009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ori-McKenney, K. M., Xu, J., Gross, S. P., Vallee, R. B.
|
|
<strong>A cytoplasmic dynein tail mutation impairs motor processivity.</strong>
|
|
Nature Cell Biol. 12: 1228-1234, 2010.
|
|
|
|
|
|
[PubMed: 21102439]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ncb2127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pearn, J.
|
|
<strong>Autosomal dominant spinal muscular atrophy: a clinical and genetic study.</strong>
|
|
J. Neurol. Sci. 38: 263-275, 1978.
|
|
|
|
|
|
[PubMed: 712386]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-510x(78)90072-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Wirth, B., Zerres, K.
|
|
<strong>Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy.</strong>
|
|
Am. J. Hum. Genet. 55: 112-119, 1994.
|
|
|
|
|
|
[PubMed: 8023839]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saul, R. A., Meyer, L. C.
|
|
<strong>Autosomal dominant spinal muscular atrophy in three generations.</strong>
|
|
Proc. Greenwood Genet. Center 4: 13-15, 1985.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Timme, W.
|
|
<strong>Progressive muscular dystrophy as an endocrine disease.</strong>
|
|
Arch. Intern. Med. 19: 79-104, 1917.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsukagoshi, H., Sugita, H., Furukawa, T., Tsubaki, T., Ono, E.
|
|
<strong>Kugelberg-Welander syndrome with dominant inheritance.</strong>
|
|
Arch. Neurol. 14: 378-381, 1966.
|
|
|
|
|
|
[PubMed: 5906462]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1966.00470100034004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsurusaki, Y., Saitoh, S., Tomizawa, K., Sudo, A., Asahina, N., Shiraishi, H., Ito, J., Tanaka, H., Doi, H., Saitsu, H., Miyake, N., Matsumoto, N.
|
|
<strong>A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance.</strong>
|
|
Neurogenetics 13: 327-332, 2012.
|
|
|
|
|
|
[PubMed: 22847149]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-012-0337-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T., Williams, M., King, C., Greenhalgh, L., Newbury-Ecob, R., Ellard, S.
|
|
<strong>Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease.</strong>
|
|
Am. J. Hum. Genet. 89: 308-312, 2011.
|
|
|
|
|
|
[PubMed: 21820100]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2011.07.002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Young, N. M.
|
|
<strong>William Stewart Young, Builder of California Institutions.</strong>
|
|
Glendale, Calif.: Arthur H. Clark Co. (pub.) 1967.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Young, P. T.
|
|
<strong>Mechanical aids for patients with muscular disability.</strong>
|
|
J. Bone Joint Surg. Am. 31: 428-430, 1949.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Young, P. T.
|
|
<strong>Personal Communication.</strong>
|
|
Claremont, Calif. 1972.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zellweger, H., Simpson, J., McCormick, W. F., Ionasescu, V.
|
|
<strong>Spinal muscular atrophy with autosomal dominant inheritance: report of a new kindred.</strong>
|
|
Neurology 22: 957-963, 1972.
|
|
|
|
|
|
[PubMed: 4673381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.22.9.957]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 9/23/2013<br>Cassandra L. Kniffin - updated : 6/27/2013<br>Cassandra L. Kniffin - updated : 4/25/2012<br>Cassandra L. Kniffin - updated : 10/20/2010
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/2/1986
|
|
</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">
|
|
carol : 01/29/2019<br>ckniffin : 01/23/2019<br>carol : 03/25/2016<br>ckniffin : 3/11/2016<br>carol : 5/1/2014<br>tpirozzi : 9/26/2013<br>ckniffin : 9/23/2013<br>carol : 7/10/2013<br>carol : 7/9/2013<br>ckniffin : 6/27/2013<br>terry : 7/5/2012<br>terry : 5/2/2012<br>carol : 4/27/2012<br>ckniffin : 4/25/2012<br>terry : 1/13/2011<br>wwang : 11/1/2010<br>ckniffin : 10/20/2010<br>alopez : 5/31/2007<br>alopez : 5/31/2007<br>carol : 3/31/2004<br>ckniffin : 3/29/2004<br>ckniffin : 3/29/2004<br>mgross : 3/17/2004<br>mimadm : 11/6/1994<br>supermim : 3/16/1992<br>carol : 11/30/1990<br>carol : 11/21/1990<br>supermim : 3/20/1990<br>ddp : 10/27/1989
|
|
</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>
|
|
|
|
|