6382 lines
690 KiB
Text
6382 lines
690 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
|
|
|
|
- #253300 - SPINAL MUSCULAR ATROPHY, TYPE I; SMA1
|
|
|
|
|
|
- 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=253300"><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">#253300</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/253300"><strong>Clinical Synopsis</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="#otherFeatures">Other 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="#diagnosis">Diagnosis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalManagement">Clinical Management</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</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, TYPE I" 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=633&Typ=Pat" title="Proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Proximal spinal muscular a… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11563&Typ=Pat" title="Proximal spinal muscular atrophy type 1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Proximal spinal muscular a… </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1352/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=253300[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="https://www.acmg.net/PDFLibrary/SMA-ACT-Sheet.pdf" class="mim-tip-hint" title="Information and resources for newborn screening and genetics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">Newborn Screening</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=70" title="Proximal spinal muscular atrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Proximal spinal muscular a…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83330" title="Proximal spinal muscular atrophy type 1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Proximal spinal muscular a…</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:13137" 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/253300" 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://omia.org/results?search_type=advanced&omia_id=000939,001164" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:13137" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:253300" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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> 64383006<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> G12.0<br />
|
|
|
|
|
|
<strong>ICD9CM:</strong> 335.0<br />
|
|
|
|
|
|
<strong>ORPHA:</strong> 70, 83330<br />
|
|
|
|
|
|
<strong>DO:</strong> 13137<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>
|
|
253300
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SPINAL MUSCULAR ATROPHY, TYPE I; SMA1
|
|
|
|
</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">
|
|
SMA I<br />
|
|
SMA, INFANTILE ACUTE FORM<br />
|
|
MUSCULAR ATROPHY, INFANTILE<br />
|
|
WERDNIG-HOFFMANN DISEASE
|
|
</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/5/232?start=-3&limit=10&highlight=232">
|
|
5q13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Spinal muscular atrophy-1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/253300"> 253300 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
|
|
SMN1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600354"> 600354 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/253300" 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">
|
|
<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/253300" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/253300" 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 recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Congenital cardiac malformations have been rarely reported in severe cases <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673355</a>]</span><br /> -
|
|
Ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
|
|
Atrial septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253366007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253366007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405752007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405752007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70142008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70142008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018817</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Respiratory failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409622000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409622000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J96.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J96.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1145670&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1145670</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</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">
|
|
|
|
- Muscle weakness, symmetric, proximal (lower limbs more affected than upper limbs) due to motor neuronopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854665&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854665</a>]</span><br /> -
|
|
Muscle atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a>, <a href="https://bioportal.bioontology.org/search?q=C0026846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br /> -
|
|
Affected children are unable to sit without support <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854666</a>]</span><br /> -
|
|
Facial muscle sparing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854667&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854667</a>]</span><br /> -
|
|
Tongue fasciculations/fibrillations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249878001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239548&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239548</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001308" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001308</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001308" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001308</a>]</span><br /> -
|
|
Normal motor conduction studies (initially) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854669&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854669</a>]</span><br /> -
|
|
EMG shows neurogenic abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846832&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846832</a>]</span><br /> -
|
|
Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br /> -
|
|
Loss of lower alpha-motor neurons in the anterior horn of the spinal cord and lower brainstem <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854670&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854670</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> PRENATAL MANIFESTATIONS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Movement </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Decreased fetal movement <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276369006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276369006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.8190" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.8190</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235659&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235659</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</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">
|
|
|
|
- Death secondary to respiratory infection or failure before age 2 years<br /> -
|
|
Onset birth to 6 months<br /> -
|
|
Incidence 1 in 6,000 to 1 in 8,000 live births<br /> -
|
|
Approximately 45% of SMA1 patients also are missing both homologs of neuronal apoptosis inhibitory protein (NAIP, <a href="/entry/600355">600355</a>), which may play a role in modifying disease severity<br /> -
|
|
Exon 7 of SMN1 is absent in 95.6% of SMA1 patients<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 survival of motor neuron 1 gene (SMN1, <a href="/entry/600354#0001">600354.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" 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 spinal muscular atrophy type I (SMA1) is caused by mutation or deletion in the telomeric copy of the SMN gene, known as SMN1 (<a href="/entry/600354">600354</a>), on chromosome 5q13.</p><p>Changes in expression of the centromeric copy of SMN, SMN2 (<a href="/entry/601627">601627</a>), are known to modify the phenotype.</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 refers to a group of autosomal recessive neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy (summary by <a href="#99" class="mim-tip-reference" title="Wirth, B. <strong>An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA).</strong> Hum. Mutat. 15: 228-237, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10679938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10679938</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10679938">Wirth, 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10679938" 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>Four types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: type I, severe infantile acute SMA, or Werdnig-Hoffman disease; type II (<a href="/entry/253550">253550</a>), or infantile chronic SMA; type III (<a href="/entry/253400">253400</a>), juvenile SMA, or Wohlfart-Kugelberg-Welander disease; and type IV (<a href="/entry/271150">271150</a>), or adult-onset SMA. All types are caused by recessive mutations in the SMN1 gene.</p><p><a href="#59" class="mim-tip-reference" title="Lunn, M. R., Wang, C. H. <strong>Spinal muscular atrophy.</strong> Lancet 371: 2120-2133, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18572081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18572081</a>] [<a href="https://doi.org/10.1016/S0140-6736(08)60921-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18572081">Lunn and Wang (2008)</a> provided a detailed review of clinical features, molecular pathogenesis, and therapeutic strategies for SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18572081" 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="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>Many groups observed the occurrence of different SMA subtypes within the same family, suggesting different manifestations of a single disease entity. <a href="#37" class="mim-tip-reference" title="Ghetti, B., Amati, A., Turra, M. V., Pacini, A., Del Vecchio, M., Guazzi, G. C. <strong>Werdnig-Hoffmann-Wohlfart-Kugelberg-Welander disease: nosological unity and clinical variability in intrafamilial cases.</strong> Acta Genet. Med. Gemellol. 20: 43-58, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5568110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5568110</a>] [<a href="https://doi.org/10.1017/s1120962300011707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5568110">Ghetti et al. (1971)</a> reported that in many families 'malignant' Werdnig-Hoffmann disease coexisted with the Werdnig-Hoffmann disease with a prolonged course, the Wohlfart-Kugelberg-Welander disease with infantile onset, and the Wohlfart-Kugelberg-Welander disease with juvenile onset. <a href="#79" class="mim-tip-reference" title="Pearn, J. K., Carter, C. O., Wilson, J. <strong>The genetic identity of acute infantile spinal muscular atrophy.</strong> Brain 96: 463-470, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4743929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4743929</a>] [<a href="https://doi.org/10.1093/brain/96.3.463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4743929">Pearn et al. (1973)</a> suggested that both the age of onset and the age of death were important in delineating this disorder and that therefore it should be called the infantile acute form of Werdnig and Hoffmann. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4743929+5568110" 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="#32" class="mim-tip-reference" title="Feingold, J., Arthuis, M., Celers, J. <strong>Genetique de l'amyotrophie spinale infantile: existence de deux formes autosomiques recessives.</strong> Ann. Genet. 20: 19-23, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/302668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">302668</a>]" pmid="302668">Feingold et al. (1977)</a> referred to 'acute' and 'chronic' forms of infantile spinal muscular atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=302668" 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="#104" class="mim-tip-reference" title="Zerres, K., Grimm, T. <strong>Genetic counseling in families with spinal muscular atrophy type Kugelberg-Welander.</strong> Hum. Genet. 65: 74-75, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6642509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6642509</a>] [<a href="https://doi.org/10.1007/BF00285033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6642509">Zerres and Grimm (1983)</a> presented a pedigree in which 2 males died at the age of 13 and 19 months, respectively, of the Werdnig-Hoffmann type of spinal muscular atrophy; a son and daughter of a great-aunt of theirs died at the age of 6 and 3.4 years, respectively, of Werdnig-Hoffmann disease, and a 59-year-old son of a great-uncle of theirs suffered from SMA of the Kugelberg-Welander type, with onset at age 12 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6642509" 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="#90" class="mim-tip-reference" title="Thomas, N. H., Dubowitz, V. <strong>The natural history of type I (severe) spinal muscular atrophy.</strong> Neuromusc. Disord. 4: 497-502, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7881295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7881295</a>] [<a href="https://doi.org/10.1016/0960-8966(94)90090-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7881295">Thomas and Dubowitz (1994)</a> found a correlation between age of onset and age of death in 2 cohorts of patients with spinal muscular atrophy, consisting of 36 and 70 patients, respectively. In one cohort, the shortest survival was 5 hours, and the longest was 19 months. In the other cohort, the mean age of onset was 1.6 months and the mean age of death was 9.6 months. The data further suggested that patients with onset before 2 months of age have a poor prognosis, with earlier death than those with slightly later onset who still fulfill the diagnostic criteria for type I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7881295" 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="#58" class="mim-tip-reference" title="Lumaka, A., Bone, D., Lukoo, R., Mujinga, N., Senga, I., Tady, B., Matthijs, G., Lukusa, T. P. <strong>Werdnig-Hoffmann disease: report of the first case clinically identified and genetically confirmed in Central Africa (Kinshasa-Congo).</strong> Genet. Counsel. 20: 349-358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20162870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20162870</a>]" pmid="20162870">Lumaka et al. (2009)</a> reported a boy from central Africa with classic type 1 SMA confirmed by genetic analysis. He presented at birth with axial hypotonia and poor spontaneous movements. By age 5.5 months, he had extreme hypotonia, was unable to hold his head up, and showed psychomotor delay. He had joint laxity, severe proximal muscle weakness, umbilical hernia, atrial septal defect, and recurrent pulmonary infections resulting in death by age 10 months. EMG studies showed evidence for an alpha-motor neuron defect. An older brother who died at 10 months was reportedly similarly affected. <a href="#58" class="mim-tip-reference" title="Lumaka, A., Bone, D., Lukoo, R., Mujinga, N., Senga, I., Tady, B., Matthijs, G., Lukusa, T. P. <strong>Werdnig-Hoffmann disease: report of the first case clinically identified and genetically confirmed in Central Africa (Kinshasa-Congo).</strong> Genet. Counsel. 20: 349-358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20162870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20162870</a>]" pmid="20162870">Lumaka et al. (2009)</a> noted that this was the first documented report of SMA type 1 in central Africa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20162870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pathologic Findings</em></strong></p><p>
|
|
Muscle biopsies of infantile spinal muscular atrophy demonstrate large numbers of round atrophic fibers and clumps of hypertrophic fibers that are type 1 by the ATPase reaction. <a href="#87" class="mim-tip-reference" title="Soubrouillard, C., Pellissier, J. F., Lepidi, H., Mancini, J., Rougon, G., Figarella-Branger, D. <strong>Expression of developmentally regulated cytoskeleton and cell surface proteins in childhood spinal muscular atrophies.</strong> J. Neurol. Sci. 133: 155-163, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8583219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8583219</a>] [<a href="https://doi.org/10.1016/0022-510x(95)00182-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8583219">Soubrouillard et al. (1995)</a> performed immunohistochemical analyses of biopsied skeletal muscle from 23 cases of infantile SMA to determine the expression of developmentally regulated cytoskeletal components, including desmin (<a href="/entry/125660">125660</a>), NCAM (<a href="/entry/116930">116930</a>), vimentin (<a href="/entry/193060">193060</a>), and embryonic and fetal forms of the myosin heavy chain. Strong NCAM and developmental myosin heavy chain expression was present in atrophic fibers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8583219" 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="otherFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimOtherFeaturesFold" id="mimOtherFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimOtherFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimOtherFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By analysis of a questionnaire-based retrospective study of 65 patients with SMA type 1, <a href="#82" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Heller, R., Berg, C., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Zerres, K. <strong>Congenital heart disease is a feature of severe infantile spinal muscular atrophy.</strong> J. Med. Genet. 45: 635-638, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18662980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18662980</a>] [<a href="https://doi.org/10.1136/jmg.2008.057950" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18662980">Rudnik-Schoneborn et al. (2008)</a> concluded that congenital heart defects may result from severe SMN deficiency. Among these patients, 4 (6%) had 1 copy of SMN2, 56 (86%) had 2 copies, and 5 (8%) had 3 copies. Three (75%) of the 4 patients with a single SMN2 copy had congenital SMA with atrial or ventricular septal defects. Six of the 56 patients with 2 copies of SMN2 showed minor cardiac anomalies that resolved spontaneously, including a patent foramen ovale (PFO) in 4 infants, associated with a hypertrophic septum in 1, a patent ductus arteriosus (PDA) in 1 patient, and a PDA combined with a PFO in another patient. A small apical ventricular septal defect along with PDA was seen in 1 patient with classic SMA I who died at 11 months. She was the child of consanguineous parents who had lost 4 other children due to alleged sudden infant death syndrome. No cardiac malformation was documented in the 5 patients with 3 SMN2 copies. In a literature review, <a href="#82" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Heller, R., Berg, C., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Zerres, K. <strong>Congenital heart disease is a feature of severe infantile spinal muscular atrophy.</strong> J. Med. Genet. 45: 635-638, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18662980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18662980</a>] [<a href="https://doi.org/10.1136/jmg.2008.057950" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18662980">Rudnik-Schoneborn et al. (2008)</a> noted that most reported SMA patients with heart defects had a severe disease course, congenital or prenatal onset, congenital contractures, respiratory distress from birth, and a very short life span, most likely associated with only 1 SMN2 copy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18662980" 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="#31" class="mim-tip-reference" title="Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N. <strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong> Nature 457: 277-280, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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/nature07677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098894">Ebert et al. (2009)</a> reported the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy type 1. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. <a href="#31" class="mim-tip-reference" title="Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N. <strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong> Nature 457: 277-280, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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/nature07677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098894">Ebert et al. (2009)</a> stated that this was the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. <a href="#31" class="mim-tip-reference" title="Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N. <strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong> Nature 457: 277-280, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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/nature07677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098894">Ebert et al. (2009)</a> suggested that since animal models for SMA1 are nonviable, the generation of these pluripotent stem cells would allow more detailed studies of the pathophysiology of SMA1 in the motor neuron. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19098894" 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="#10" class="mim-tip-reference" title="Brandt, S. <strong>Hereditary factors in infantile progressive muscular atrophy: study of one hundred and twelve cases in seventy families.</strong> Am. J. Dis. Child. 78: 226-236, 1949."None>Brandt (1949)</a> reported a large study of familial infantile progressive muscular atrophy involving 112 cases in 70 families. Segregation analysis yielded results consistent with autosomal recessive inheritance. Almost 6% of the parents were consanguineous, a value 8 times that in controls.</p><p><a href="#60" class="mim-tip-reference" title="Marquardt, J. E., MacLowry, J., Perry, R. E. <strong>Infantile progressive spinal muscular atrophy in identical Negro twins.</strong> New Eng. J. Med. 267: 386-388, 1962.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14470139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14470139</a>] [<a href="https://doi.org/10.1056/NEJM196208232670804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14470139">Marquardt et al. (1962)</a>, among others, described the disorder in twins. <a href="#46" class="mim-tip-reference" title="Hogenhuis, L. A. H., Spaulding, S. W., Engel, W. K. <strong>Neuronal RNA metabolism in infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) studied by radioautography: a new technic in the investigation of neurological disease.</strong> J. Neuropath. Exp. Neurol. 26: 335-341, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6022173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6022173</a>] [<a href="https://doi.org/10.1097/00005072-196704000-00010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6022173">Hogenhuis et al. (1967)</a> reported studies of a Chinese family in which 4 of 8 sibs succumbed to Werdnig-Hoffmann disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14470139+6022173" 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="diagnosis" class="mim-anchor"></a>
|
|
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>See <a href="/entry/600354">600354</a> for details on the molecular diagnosis of SMA.</p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
|
|
<a href="#28" class="mim-tip-reference" title="Daniels, R. J., Suthers, G. K., Morrison, K. E., Thomas, N. H., Francis, M. J., Mathew, C. G., Loughlin, S., Heiberg, A., Wood, D., Dubowitz, V., Davies, K. E. <strong>Prenatal prediction of spinal muscular atrophy.</strong> J. Med. Genet. 29: 165-170, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348091</a>] [<a href="https://doi.org/10.1136/jmg.29.3.165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1348091">Daniels et al. (1992)</a> and <a href="#65" class="mim-tip-reference" title="Melki, J., Abdelhak, S., Burlet, P., Raclin, V., Kaplan, J., Spiegel, R., Gilgenkrantz, S., Philip, N., Chauvet, M.-L., Dumez, Y., Briard, M.-L., Frezal, J., Munnich, A. <strong>Prenatal prediction of Werdnig-Hoffmann disease using linked polymorphic DNA probes.</strong> J. Med. Genet. 29: 171-174, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348092</a>] [<a href="https://doi.org/10.1136/jmg.29.3.171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1348092">Melki et al. (1992)</a> demonstrated the feasibility of prenatal diagnosis of SMA by the linkage principle. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1348091+1348092" 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="#96" class="mim-tip-reference" title="Wirth, B., Rudnik-Schoneborn, S., Hahnen, E., Rohrig, D., Zerres, K. <strong>Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2-q13.3): molecular genetics and clinical experience in 109 cases.</strong> Prenatal Diag. 15: 407-417, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7644431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7644431</a>] [<a href="https://doi.org/10.1002/pd.1970150503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7644431">Wirth et al. (1995)</a> presented their experience with 109 prenatal diagnoses performed in 91 families at risk of SMA by use of polymorphic microsatellites in the region 5q11.2-q13.3. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be at more than 99% risk of developing the disease, while in 7 additional pregnancies no exact prediction could be made due to a recombination event in 1 parental haplotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7644431" 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="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#76" class="mim-tip-reference" title="Oprea, G. E., Kroeber, S., McWhorter, M. L., Rossoll, W., Mueller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., Wirth, B. <strong>Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy.</strong> Science 320: 524-527, 2008. Note: Erratum: Science 384: eadq4773, 2024."None>Oprea et al. (2008)</a> discovered that unaffected SMN1-deleted females exhibit significantly higher expression of plastin-3 (PLS3; <a href="/entry/300131">300131</a>) than their SMA-affected counterparts. The authors demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN downregulation in motor neurons of SMA mouse embryos and in zebrafish. <a href="#76" class="mim-tip-reference" title="Oprea, G. E., Kroeber, S., McWhorter, M. L., Rossoll, W., Mueller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., Wirth, B. <strong>Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy.</strong> Science 320: 524-527, 2008. Note: Erratum: Science 384: eadq4773, 2024."None>Oprea et al. (2008)</a> concluded that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.</p><p><a href="#93" class="mim-tip-reference" title="Wen, H.-L., Lin, Y.-T., Ting, C.-H., Lin-Chao, S., Li, H., Hsieh-Li, H. M. <strong>Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy.</strong> Hum. Molec. Genet. 19: 1766-1778, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20176735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20176735</a>] [<a href="https://doi.org/10.1093/hmg/ddq058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20176735">Wen et al. (2010)</a> described a potential link between stathmin (STMN1; <a href="/entry/151442">151442</a>) and microtubule defects in SMA. Stathmin was identified by screening Smn-knockdown NSC34 cells through proteomics analysis. Stathmin was aberrantly upregulated in vitro and in vivo, leading to a decreased level of polymerized tubulin, which was correlated with disease severity. Reduced microtubule densities and beta-3-tubulin (TUBB3; <a href="/entry/602661">602661</a>) levels in distal axons of affected SMA-like mice and an impaired microtubule network in Smn-deficient cells were observed, suggesting an involvement of stathmin in those microtubule defects. Furthermore, knockdown of stathmin restored the microtubule network defects of Smn-deficient cells, promoted axon outgrowth, and reduced the defect in mitochondria transport in SMA-like motor neurons. The authors concluded that aberrant stathmin levels may play a detrimental role in SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20176735" 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="#52" class="mim-tip-reference" title="Kye, M. J., Niederst, E. D., Wertz, M. H., Goncalves, I. C. G., Akten, B., Dover, K. Z., Peters, M., Riessland, M., Neveu, P., Wirth, B., Kosik, K. S., Sardi, S. P., Monani, U. R., Passini, M. A., Sahin, M. <strong>SMN regulates axonal local translation via miR-183/mTOR pathway.</strong> Hum. Molec. Genet. 23: 6318-6331, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25055867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25055867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25055867[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddu350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25055867">Kye et al. (2014)</a> found that expression of microRNA-183 (MIR183; <a href="/entry/611608">611608</a>), but not its primary transcript, was increased in Smn-knockdown rat primary neurons, concomitant with impaired axonal growth, impaired local translation of Mtor (<a href="/entry/601231">601231</a>) in neurites, and reduced Mtor pathway-dependent neurite protein synthesis. Mir183 was also elevated in SMA model mice and in SMA patient-derived fibroblasts. Codepletion of Mir183 and Smn in rat neurons rescued the axonal phenotype and increased Mtor expression in neurites. <a href="#52" class="mim-tip-reference" title="Kye, M. J., Niederst, E. D., Wertz, M. H., Goncalves, I. C. G., Akten, B., Dover, K. Z., Peters, M., Riessland, M., Neveu, P., Wirth, B., Kosik, K. S., Sardi, S. P., Monani, U. R., Passini, M. A., Sahin, M. <strong>SMN regulates axonal local translation via miR-183/mTOR pathway.</strong> Hum. Molec. Genet. 23: 6318-6331, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25055867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25055867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25055867[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddu350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25055867">Kye et al. (2014)</a> identified an Mir183-binding site in the 3-prime UTR of the Mtor transcript, and Mir183 bound directly to this site and inhibited Mtor translation. Inhibition of Mir183 in vivo partly alleviated the disease phenotype in SMA model mice. <a href="#52" class="mim-tip-reference" title="Kye, M. J., Niederst, E. D., Wertz, M. H., Goncalves, I. C. G., Akten, B., Dover, K. Z., Peters, M., Riessland, M., Neveu, P., Wirth, B., Kosik, K. S., Sardi, S. P., Monani, U. R., Passini, M. A., Sahin, M. <strong>SMN regulates axonal local translation via miR-183/mTOR pathway.</strong> Hum. Molec. Genet. 23: 6318-6331, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25055867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25055867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25055867[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddu350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25055867">Kye et al. (2014)</a> concluded that axonal MIR183 and the MTOR pathway contribute to SMA pathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25055867" 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="clinicalManagement" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#21" class="mim-tip-reference" title="Chang, J.-G., Hsieh-Li, H.-M., Jong, Y.-J., Wang, N. M., Tsai, C.-H., Li, H. <strong>Treatment of spinal muscular atrophy by sodium butyrate.</strong> Proc. Nat. Acad. Sci. 98: 9808-9813, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11504946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11504946</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11504946[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.171105098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11504946">Chang et al. (2001)</a> reported results suggesting that sodium butyrate may be helpful in the treatment of SMA. They found that this agent increased the amount of exon 7-containing SMN protein in lymphoid cell lines from SMA patients by changing the alternative splicing pattern of exon 7 in the SMN2 gene. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all 3 types of SMA-like mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11504946" 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="#12" class="mim-tip-reference" title="Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F. A., Raschke, H., Blumcke, I., Eyupoglu, I. Y., Wirth, B. <strong>Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.</strong> Hum. Molec. Genet. 12: 2481-2489, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915451</a>] [<a href="https://doi.org/10.1093/hmg/ddg256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12915451">Brichta et al. (2003)</a> showed that in fibroblast cultures derived from SMA patients treated with therapeutic doses of valproic acid (VPA), the level of full-length SMN2 mRNA/protein increased 2- to 4-fold. This upregulation of SMN was most likely attributable to increased levels of HTRA2-beta-1 (see <a href="/entry/606441">606441</a>) as well as to SMN gene transcription activation. VPA was also able to increase SMN protein levels through transcription activation in organotypic hippocampal rat brain slices. Additionally, valproic acid increased the expression of other serine-arginine (SR) family proteins, which may have important implications for other disorders affected by alternative splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of valproic acid (VPA) treatment in 10 SMA carriers and 20 patients with SMA1, SMA2, or SMA3, <a href="#13" class="mim-tip-reference" title="Brichta, L., Holker, I., Haug, K., Klockgether, T., Wirth, B. <strong>In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate.</strong> Ann. Neurol. 59: 970-975, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607616</a>] [<a href="https://doi.org/10.1002/ana.20836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16607616">Brichta et al. (2006)</a> found that VPA increased peripheral blood full-length SMN mRNA and protein levels in 7 carriers, increased full-length SMN2 mRNA in 7 patients, and left full-length SMN2 mRNA levels unchanged or decreased in 13 patients. The effect on protein levels in carriers was more pronounced than on mRNA levels, and the variability in augmentation among carriers and patients suggested to the authors that valproic acid interferes with transcription of genes encoding translation factors or regulates translation or SMN protein stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16607616" 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 fibroblast cultures from patients with SMA I, SMA II, or SMA III, <a href="#3" class="mim-tip-reference" title="Andreassi, C., Angelozzi, C., Tiziano, F. D., Vitali, T., De Vincenzi, E., Boninsegna, A., Villanova, M., Bertini, E., Pini, A., Neri, G., Brahe, C. <strong>Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy.</strong> Europ. J. Hum. Genet. 12: 59-65, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14560316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14560316</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14560316">Andreassi et al. (2004)</a> found a significant increase in SMN2 gene expression (increase in SMN2 transcripts of 50 to 160% in SMA1, and of 80 to 400% in SMA2 and SMA3) and a more moderate increase in SMN protein expression in response to treatment with 4-phenylbutyrate (PBA). PBA treatment also resulted in an increase in the number of SMN-containing nuclear structures (GEMS). The authors suggested a potential use for PBA in treatment of various types of SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14560316" 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="#40" class="mim-tip-reference" title="Grzeschik, S. M., Ganta, M., Prior, T. W., Heavlin, W. D., Wang, C. H. <strong>Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells.</strong> Ann. Neurol. 58: 194-202, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16049920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16049920</a>] [<a href="https://doi.org/10.1002/ana.20548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16049920">Grzeschik et al. (2005)</a> reported that cultured lymphocytes from patients with SMA showed increased production of the full-length SMN mRNA and protein in response to treatment with hydroxyurea. The findings suggested that hydroxyurea promoted inclusion of exon 7 during SMN2 transcription. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16049920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of questionnaire-based data on 143 SMA patients, <a href="#77" class="mim-tip-reference" title="Oskoui, M., Levy, G., Garland, C. J., Gray, J. M., O'Hagen, J., De Vivo, D. C., Kaufmann, P. <strong>The changing natural history of spinal muscular atrophy type 1.</strong> Neurology 69: 1931-1936, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998484</a>] [<a href="https://doi.org/10.1212/01.wnl.0000290830.40544.b9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17998484">Oskoui et al. (2007)</a> found that patients born from 1995 to 2006 had a 70% reduction in the risk of death compared to patients born from 1980 to 1994. However, when controlling for demographic and clinical care variables, the association was no longer significant. Treatment with ventilation for more than 16 hours per day, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feedings showed a significant effect in reducing the risk of death. An amino acid diet had no significant effect on survival. <a href="#77" class="mim-tip-reference" title="Oskoui, M., Levy, G., Garland, C. J., Gray, J. M., O'Hagen, J., De Vivo, D. C., Kaufmann, P. <strong>The changing natural history of spinal muscular atrophy type 1.</strong> Neurology 69: 1931-1936, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998484</a>] [<a href="https://doi.org/10.1212/01.wnl.0000290830.40544.b9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17998484">Oskoui et al. (2007)</a> concluded that the increased use of specific proactive management tools has been successful in enhancing survival of patients with SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17998484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Angelozzi, C., Borgo, F., Tiziano, F. D., Martella, A., Neri, G., Brahe, C. <strong>Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells.</strong> J. Med. Genet. 45: 29-31, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932121</a>] [<a href="https://doi.org/10.1136/jmg.2007.051177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17932121">Angelozzi et al. (2008)</a> found that salbutamol increased full-length SMN2 mRNA transcript levels in fibroblasts derived from patients with SMA I, II, and III. The maximum increase (over 200%) was observed after 30 to 60 minutes. This rapid rise correlated with decreased levels of SMN2 with deletion of exon 7. Salbutamol treatment also resulted in increased SMN protein levels and nuclear gems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932121" 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="#102" class="mim-tip-reference" title="Yuo, C.-Y., Lin, H.-H., Chang, Y.-S., Yang, W.-K., Chang, J.-G. <strong>5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells.</strong> Ann. Neurol. 63: 26-34, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17924536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17924536</a>] [<a href="https://doi.org/10.1002/ana.21241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17924536">Yuo et al. (2008)</a> found that treatment of SMA lymphoid cell lines with an Na+/H+ exchange inhibitor resulted in increased expression of SMN2 mRNA with exon 7 and increased SMN protein production in SMA cells. The underlying mechanism appeared to be upregulation of the splicing factor SRp20 (<a href="/entry/603364">603364</a>) in the nucleus. The findings were consistent with an effect of cellular pH on SMN splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17924536" 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="#31" class="mim-tip-reference" title="Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N. <strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong> Nature 457: 277-280, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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/nature07677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098894">Ebert et al. (2009)</a> reported the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy type 1. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. <a href="#31" class="mim-tip-reference" title="Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N. <strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong> Nature 457: 277-280, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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/nature07677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098894">Ebert et al. (2009)</a> stated that this was the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. <a href="#31" class="mim-tip-reference" title="Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N. <strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong> Nature 457: 277-280, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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/nature07677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098894">Ebert et al. (2009)</a> suggested that since animal models for SMA1 are nonviable, the generation of these pluripotent stem cells would allow more detailed studies of the pathophysiology of SMA1 in the motor neuron. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19098894" 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>Through chemical screening and optimization, <a href="#73" class="mim-tip-reference" title="Naryshkin, N. A., Weetall, M., Dakka, A., Narasimhan, J., Zhao, X., Feng, Z., Ling, K. K. Y., Karp, G. M., Qi, H., Woll, M. G., Chen, G., Zhang, N., and 36 others. <strong>SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy.</strong> Science 345: 688-693, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25104390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25104390</a>] [<a href="https://doi.org/10.1126/science.1250127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25104390">Naryshkin et al. (2014)</a> identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 mRNA with high selectivity. Administration of these compounds to delta-7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25104390" 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 homozygosity testing of 4 consanguineous families with SMA type I, <a href="#38" class="mim-tip-reference" title="Gilliam, T. C., Brzustowicz, L. M., Castilla, L. H., Lehner, T., Penchaszadeh, G. K., Daniels, R. J., Byth, B. C., Knowles, J., Hislop, J. E., Shapira, Y., Dubowitz, V., Munsat, T. L., Ott, J., Davies, K. E. <strong>Genetic homogeneity between acute and chronic forms of spinal muscular atrophy.</strong> Nature 345: 823-825, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1972783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1972783</a>] [<a href="https://doi.org/10.1038/345823a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1972783">Gilliam et al. (1990)</a> linked the disorder to chromosome 5q11.2-q13.3, the same region to which the more chronic forms SMA II and SMA III had been mapped. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1972783" 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="#67" class="mim-tip-reference" title="Melki, J., Sheth, P., Abdelhak, S., Burlet, P., Bachelot, M.-F., Lathrop, M. G., Frezal, J., Munnich, A., the French Spinal Muscular Atrophy Investigators. <strong>Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14.</strong> Lancet 336: 271-273, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973971</a>] [<a href="https://doi.org/10.1016/0140-6736(90)91803-i" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1973971">Melki et al. (1990)</a> independently demonstrated that SMA type I, like types II and III, was linked to markers at chromosome 5q12-q14. By in situ hybridization of 2 markers closely flanking the SMA I gene, <a href="#61" class="mim-tip-reference" title="Mattei, M.-G., Melki, J., Bachelot, M.-F., Abdelhak, S., Burlet, P., Frezal, J., Munnich, A. <strong>In situ hybridization of two markers closely flanking the spinal muscular atrophy gene to 5q12-q13.3.</strong> Cytogenet. Cell Genet. 57: 112-113, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1914518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1914518</a>] [<a href="https://doi.org/10.1159/000133125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1914518">Mattei et al. (1991)</a> refined the assignment to 5q12-q13.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1973971+1914518" 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="#28" class="mim-tip-reference" title="Daniels, R. J., Suthers, G. K., Morrison, K. E., Thomas, N. H., Francis, M. J., Mathew, C. G., Loughlin, S., Heiberg, A., Wood, D., Dubowitz, V., Davies, K. E. <strong>Prenatal prediction of spinal muscular atrophy.</strong> J. Med. Genet. 29: 165-170, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348091</a>] [<a href="https://doi.org/10.1136/jmg.29.3.165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1348091">Daniels et al. (1992)</a> used in situ hybridization to refine the mapping of SMA I to 5q12.2-q13 near marker D5S6. <a href="#14" class="mim-tip-reference" title="Brzustowicz, L. M., Kleyn, P. W., Boyce, F. M., Lien, L. L., Monaco, A. P., Penchaszadeh, G. K., Das, K., Wang, C. H., Munsat, T. L., Ott, J., Kunkel, L. M., Gilliam, T. C. <strong>Fine-mapping of the spinal muscular atrophy locus to a region flanked by MAP1B and D5S6.</strong> Genomics 13: 991-998, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505990</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90012-h" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1505990">Brzustowicz et al. (1992)</a> identified 2 flanking loci, MAP1B (<a href="/entry/157129">157129</a>) and D5S6, which are separated by an interval of approximately 2 cM. <a href="#98" class="mim-tip-reference" title="Wirth, B., Voosen, B., Rohrig, D., Knapp, M., Piechaczek, B., Rudnik-Schoneborn, S., Zerres, K. <strong>Fine mapping and narrowing of the genetic interval of the spinal muscular atrophy region by linkage studies.</strong> Genomics 15: 113-118, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432521</a>] [<a href="https://doi.org/10.1006/geno.1993.1018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432521">Wirth et al. (1993)</a> narrowed the assignment to a region of about 4 cM and defined a new proximal genetic border by the locus D5S125. The closest marker on the distal side of SMA was found to be MAP1B, which has its 5-prime end directed toward the centromere. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1348091+1505990+8432521" 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="#56" class="mim-tip-reference" title="Lien, L. L., Boyce, F. M., Kleyn, P., Brzustowicz, L. M., Menninger, J., Ward, D. C., Gilliam, T. C., Kunkel, L. M. <strong>Mapping of a gene encoding a dystrophin cross-reactive protein in close proximity to the spinal muscular atrophy locus. (Abstract)</strong> Am. J. Hum. Genet. 49 (suppl.): 412, 1991."None>Lien et al. (1991)</a> used a polyclonal antiserum directed against the C-terminal domain of dystrophin (<a href="/entry/300377">300377</a>) to isolate a cDNA encoding an antigenically cross-reactive protein. Physical mapping of this gene placed it at 5q13 in close proximity to the SMA locus. A genetic linkage analysis of SMA families using a dinucleotide repeat polymorphism related to the dystrophin-like gene showed tight linkage to SMA mutations. The brain-specific expression of the gene likewise suggested possible association with SMA.</p><p>By a combination of genetic and physical mapping, <a href="#66" class="mim-tip-reference" title="Melki, J., Lefebvre, S., Burglen, L., Burlet, P., Clermont, O., Millasseau, P., Reboullet, S., Benichou, B., Zeviani, M., Le Paslier, D., Cohen, D., Weissenbach, J., Munnich, A. <strong>De novo and inherited deletions of the 5q13 region in spinal muscular atrophies.</strong> Science 264: 1474-1477, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7910982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7910982</a>] [<a href="https://doi.org/10.1126/science.7910982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7910982">Melki et al. (1994)</a> constructed a yeast artificial chromosome (YAC) contig of the 5q13 region spanning the SMN disease locus and showing the presence of low copy repeats. Analysis of allele segregation at the closest genetic loci in 201 SMA families demonstrated inherited and de novo deletions in 9 unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18% of SMA type I patients by the observation of marked deficiency of heterozygosity for the loci studied. The results indicated that deletion events were statistically associated with the severe form of spinal muscular atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7910982" 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="#91" class="mim-tip-reference" title="Thompson, T. G., DiDonato, C. J., Simard, L. R., Ingraham, S. E., Burghes, A. H. M., Crawford, T. O., Rochette, C., Mendell, J. R., Wasmuth, J. J. <strong>A novel cDNA detects homozygous microdeletions in greater than 50% of type I spinal muscular atrophy patients..</strong> Nature Genet. 9: 56-62, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7704025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7704025</a>] [<a href="https://doi.org/10.1038/ng0195-56" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7704025">Thompson et al. (1995)</a> identified several coding sequences unique to the SMA region. A genomic fragment detected by 1 cDNA was homozygously deleted in 17 of 29 (58%) type I SMA patients. Only 2 of 235 unaffected controls showed the deletion, and both were carriers of the disease. These data suggested that deletion of at least part of this novel gene is directly related to the phenotype of SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7704025" 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><a href="#6" class="mim-tip-reference" title="Biros, I., Forrest, S. <strong>Spinal muscular dystrophy: untangling the knot?</strong> J. Med. Genet. 36: 1-8, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950358</a>]" pmid="9950358">Biros and Forrest (1999)</a>, <a href="#99" class="mim-tip-reference" title="Wirth, B. <strong>An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA).</strong> Hum. Mutat. 15: 228-237, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10679938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10679938</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10679938">Wirth (2000)</a>, and <a href="#75" class="mim-tip-reference" title="Ogino, S., Wilson, R. B. <strong>Spinal muscular atrophy: molecular genetics and diagnosis.</strong> Expert Rev. Molec. Diagn. 4: 15-29, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14711346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14711346</a>] [<a href="https://doi.org/10.1586/14737159.4.1.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14711346">Ogino and Wilson (2004)</a> provided reviews of the complex molecular basis of SMA. SMN1 and SMN2 lie within the telomeric and centromeric halves, respectively, of a large inverted repeat on chromosome 5q. The coding sequence of SMN2 differs from that of SMN1 by a single nucleotide in exon 7 (840C-T), which results in decreased transcription and deficiency of the normal stable SMN protein. Approximately 94% of individuals with SMA lack both copies of SMN1 exon 7, resulting in substantial loss of the protein. Loss of exon 7 can result from deletion or the 840C-T change, in which SMN1 is essentially converted to SMN2 (gene conversion) (<a href="#57" class="mim-tip-reference" title="Lorson, C. L., Hahnen, E., Androphy, E. J., Wirth, B. <strong>A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy.</strong> Proc. Nat. Acad. Sci. 96: 6307-6311, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10339583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10339583</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10339583[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.11.6307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10339583">Lorson et al., 1999</a>). Loss of SMN1 can also occur by other mechanisms, such as large deletions or point mutations. Most of the SMN protein is derived from the SMN1 gene; however, the SMN2 gene can contribute a small amount of SMN protein, thus modifying the genotype. For a detailed discussion of the molecular genetics of SMA, see <a href="/entry/600354">600354</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14711346+10679938+9950358+10339583" 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="#54" class="mim-tip-reference" title="Lefebvre, S., Burglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., Le Paslier, D., Frezal, J., Cohen, D., Weissenbach, J., Munnich, A., Melki, J. <strong>Identification and characterization of a spinal muscular atrophy-determining gene.</strong> Cell 80: 155-165, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813012</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90460-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813012">Lefebvre et al. (1995)</a> identified the SMN gene, which they termed 'survival motor neuron,' within the SMA candidate region on chromosome 5q13, and demonstrated deletion or disruption of the gene in 226 of 229 patients with SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7813012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a separate publication accompanying that by <a href="#54" class="mim-tip-reference" title="Lefebvre, S., Burglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., Le Paslier, D., Frezal, J., Cohen, D., Weissenbach, J., Munnich, A., Melki, J. <strong>Identification and characterization of a spinal muscular atrophy-determining gene.</strong> Cell 80: 155-165, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813012</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90460-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813012">Lefebvre et al. (1995)</a>, <a href="#80" class="mim-tip-reference" title="Roy, N., Mahadevan, M. S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X., Salih, M., Aubry, H., Tamai, K., Guan, X., Ioannou, P., Crawford, T. O., de Jong, P. J., Surh, L., Ikeda, J.-E., Korneluk, R. G., MacKenzie, A. <strong>The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.</strong> Cell 80: 167-178, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813013</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90461-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813013">Roy et al. (1995)</a> identified a different gene on chromosome 5q13.1, neuronal apoptosis inhibitory protein (NAIP; <a href="/entry/600355">600355</a>). They found that the first 2 coding exons of this gene were deleted in approximately 67% of type I SMA chromosomes compared with 2% of non-SMA chromosomes, and reverse transcriptase-PCR analysis revealed internally deleted and mutated forms of the NAIP transcript in type I SMA individuals and not in unaffected individuals. <a href="#80" class="mim-tip-reference" title="Roy, N., Mahadevan, M. S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X., Salih, M., Aubry, H., Tamai, K., Guan, X., Ioannou, P., Crawford, T. O., de Jong, P. J., Surh, L., Ikeda, J.-E., Korneluk, R. G., MacKenzie, A. <strong>The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.</strong> Cell 80: 167-178, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813013</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90461-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813013">Roy et al. (1995)</a> suggested that mutations in the NAIP locus resulted in a failure of a normally occurring inhibition of motor neuron apoptosis that occurs during development, thus contributing to the SMA phenotype. In a discussion of these seemingly discordant findings, <a href="#55" class="mim-tip-reference" title="Lewin, B. <strong>Genes for SMA: multum in parvo.</strong> Cell 80: 1-5, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813005</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90442-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813005">Lewin (1995)</a> suggested that a mutation in either of the 2 genes could result in SMA or that a mutation in both genes was necessary for the disease. <a href="#39" class="mim-tip-reference" title="Gilliam, T. C. <strong>Is the spinal muscular atrophy gene found?</strong> Nature Med. 1: 124-127, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585007</a>] [<a href="https://doi.org/10.1038/nm0295-124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585007">Gilliam (1995)</a> discussed the evidence that either the NAIP gene or the SMN gene, or perhaps both, are involved in the causation of SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7585007+7813005+7813013+7813012" 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="#62" class="mim-tip-reference" title="Matthijs, G., Schollen, E., Legius, E., Devriendt, K., Goemans, N., Kayserili, H., Apak, M. Y., Cassiman, J.-J. <strong>Unusual molecular findings in autosomal recessive spinal muscular atrophy.</strong> J. Med. Genet. 33: 469-474, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782046</a>] [<a href="https://doi.org/10.1136/jmg.33.6.469" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8782046">Matthijs et al. (1996)</a> identified homozygous deletion of exon 7 of the SMN1 gene in 34 of 38 patients with SMA. Of these 34 patients, the deletion was associated with homozygous deletion of exon 8 in 31 patients and with heterozygous deletion of exon 8 in 2 patients; both copies of exon 8 were present in 1 patient. In 1 family, a normal father of the proband had only 1 copy of the SMN gene and lacked both copies of the SMN2 gene, showing that a reduction of the total number of SMN genes to a single SMN copy is compatible with normal life. In another family, a de novo deletion of a paternal SMN2 gene was found in a normal sister of a girl with SMA I. <a href="#62" class="mim-tip-reference" title="Matthijs, G., Schollen, E., Legius, E., Devriendt, K., Goemans, N., Kayserili, H., Apak, M. Y., Cassiman, J.-J. <strong>Unusual molecular findings in autosomal recessive spinal muscular atrophy.</strong> J. Med. Genet. 33: 469-474, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782046</a>] [<a href="https://doi.org/10.1136/jmg.33.6.469" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8782046">Matthijs et al. (1996)</a> suggested that 'this region of chromosome 5q shows some special characteristics which should lead to caution' in the molecular diagnosis of SMA I. Deletions of the SMN gene were not found in 4 of the patients with SMA I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8782046" 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="#41" class="mim-tip-reference" title="Hahnen, E., Schonling, J., Rudnik-Schoneborn, S., Zerres, K., Wirth, B. <strong>Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease.</strong> Am. J. Hum. Genet. 59: 1057-1065, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900234</a>]" pmid="8900234">Hahnen et al. (1996)</a> reported molecular analysis of 42 SMA patients who carried homozygous deletions of exon 7 but not of exon 8 in the SMN1 gene. Additional homozygous deletions of exon 8 in the SMN2 gene were found in 2 of the patients. By a simple PCR test, <a href="#41" class="mim-tip-reference" title="Hahnen, E., Schonling, J., Rudnik-Schoneborn, S., Zerres, K., Wirth, B. <strong>Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease.</strong> Am. J. Hum. Genet. 59: 1057-1065, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900234</a>]" pmid="8900234">Hahnen et al. (1996)</a> demonstrated the existence of hybrid SMN genes (i.e., genes composed of both the centromeric SMN2 and the telomeric SMN1). They reported a high frequency of hybrid SMN genes in SMA patients with Czech or Polish background. <a href="#41" class="mim-tip-reference" title="Hahnen, E., Schonling, J., Rudnik-Schoneborn, S., Zerres, K., Wirth, B. <strong>Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease.</strong> Am. J. Hum. Genet. 59: 1057-1065, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900234</a>]" pmid="8900234">Hahnen et al. (1996)</a> identified a single haplotype for half of the hybrid genes analyzed, suggesting that in these cases the SMA chromosomes shared a common origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Alias, L., Bernal, S., Fuentes-Prior, P., Barcelo, M. J., Also, E., Martinez-Hernandez, R., Rodriguez-Alvarez, F. J., Martin, Y., Aller, E., Grau, E., Pecina, A., Antinolo, G., Galan, E., Rosa, A. L., Fernandez-Burriel, M., Borrego, S., Millan, J. M., Hernandez-Chico, C., Baiget, M., Tizzano, E. F. <strong>Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene.</strong> Hum. Genet. 125: 29-39, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19050931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19050931</a>] [<a href="https://doi.org/10.1007/s00439-008-0598-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19050931">Alias et al. (2009)</a> found homozygous absence of SMN1 exons 7 and 8 in 671 (90%) of 745 Spanish SMA patients. Thirty-seven patients (5%) had homozygous absence of exon 7 but not exon 8, due to the presence of hybrid genes. The majority of the remaining 5% of patients had smaller deletions or point mutations. However, only 1 mutant allele was identified in 7 (0.9%) patients. Data stratification by SMA type showed that females had a significantly higher frequency of type I SMA compared to males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19050931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Modifying Factors</em></strong></p><p>
|
|
<a href="#89" class="mim-tip-reference" title="Stratigopoulos, G., Lanzano, P., Deng, L., Guo, J., Kaufmann, P., Darras, B., Finkel, R., Tawil, R., McDermott, M. P., Martens, W., Devivo, D. C., Chung, W. K. <strong>Association of plastin 3 expression with disease severity in spinal muscular atrophy only in postpubertal females.</strong> Arch. Neurol. 67: 1252-1256, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20937953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20937953</a>] [<a href="https://doi.org/10.1001/archneurol.2010.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20937953">Stratigopoulos et al. (2010)</a> evaluated blood levels of PLS3 (<a href="/entry/300131">300131</a>) mRNA transcripts in 88 patients with SMA, including 29 males under age 11 years, 12 males over age 11, 29 prepubertal girls, and 18 postpubertal girls in an attempt to examine whether PLS3 was a modifier of the phenotype. PLS3 expression was decreased in the older patients of both sexes. However, expression correlated with phenotype only in postpubertal girls: expression was greatest in those with SMA type III, intermediate in those with SMA type II, and lowest in those with SMA type I, and correlated with residual motor function as well as SMN2 copy number. <a href="#89" class="mim-tip-reference" title="Stratigopoulos, G., Lanzano, P., Deng, L., Guo, J., Kaufmann, P., Darras, B., Finkel, R., Tawil, R., McDermott, M. P., Martens, W., Devivo, D. C., Chung, W. K. <strong>Association of plastin 3 expression with disease severity in spinal muscular atrophy only in postpubertal females.</strong> Arch. Neurol. 67: 1252-1256, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20937953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20937953</a>] [<a href="https://doi.org/10.1001/archneurol.2010.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20937953">Stratigopoulos et al. (2010)</a> concluded that the PLS3 gene may be an age- and/or puberty-specific and sex-specific modifier of SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20937953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>For a detailed discussion of genotype/phenotype correlations in spinal muscular atrophy, see <a href="/entry/600354">600354</a>.</p><p><a href="#17" class="mim-tip-reference" title="Burlet, P., Burglen, L., Clermont, O., Lefebvre, S., Viollet, L., Munnich, A., Melki, J. <strong>Large scale deletions of the 5q13 region are specific to Werdnig-Hoffmann disease.</strong> J. Med. Genet. 33: 281-283, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8730281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8730281</a>] [<a href="https://doi.org/10.1136/jmg.33.4.281" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8730281">Burlet et al. (1996)</a> found large-scale deletions involving both the SMN gene and its upstream (C212-C272) and downstream (NAIP) flanking markers in 43% of 106 unrelated SMA patients. However, they noted that smaller rearrangements can still result in disease, since 27% of patients with severe disease lacked only the SMN gene. They also pointed out that deletion of the SMN gene may produce mild disease and referred to an article by Cobben et al. (l995) in which deletions of the SMN gene were found in unaffected sibs of patients with SMA. <a href="#17" class="mim-tip-reference" title="Burlet, P., Burglen, L., Clermont, O., Lefebvre, S., Viollet, L., Munnich, A., Melki, J. <strong>Large scale deletions of the 5q13 region are specific to Werdnig-Hoffmann disease.</strong> J. Med. Genet. 33: 281-283, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8730281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8730281</a>] [<a href="https://doi.org/10.1136/jmg.33.4.281" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8730281">Burlet et al. (1996)</a> suggested that other genetic mechanisms might be involved in the variable clinical expression of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8730281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using pulsed field gel electrophoresis to map deletions in the SMN gene, <a href="#19" class="mim-tip-reference" title="Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K. <strong>Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.</strong> Am. J. Hum. Genet. 61: 40-50, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245983</a>] [<a href="https://doi.org/10.1086/513886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245983">Campbell et al. (1997)</a> found that mutations in SMA types II and III, previously classed as deletions, were in fact due to gene-conversion events in which the telomeric SMN1 was replaced by its centromeric counterpart, SMN2. This resulted in a greater number of SMN2 copies in type II and type III patients compared with type I patients and enabled a genotype/phenotype correlation to be made. <a href="#19" class="mim-tip-reference" title="Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K. <strong>Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.</strong> Am. J. Hum. Genet. 61: 40-50, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245983</a>] [<a href="https://doi.org/10.1086/513886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245983">Campbell et al. (1997)</a> also demonstrated individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explained why no consensus map of this region of 5q had been produced. They suggested that this DNA variation may be due to a 'midisatellite' array, which would promote the observed high deletion and gene conversion rate. <a href="#16" class="mim-tip-reference" title="Burghes, A. H. M. <strong>When is a deletion not a deletion? When it is converted. (Editorial)</strong> Am. J. Hum. Genet. 61: 9-15, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245977</a>] [<a href="https://doi.org/10.1086/513913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245977">Burghes (1997)</a> discussed the significance of the findings of <a href="#19" class="mim-tip-reference" title="Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K. <strong>Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.</strong> Am. J. Hum. Genet. 61: 40-50, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245983</a>] [<a href="https://doi.org/10.1086/513886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245983">Campbell et al. (1997)</a> and presented a model (Figure 3) of alleles present in the normal population and in severe and mild forms of SMA. <a href="#19" class="mim-tip-reference" title="Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K. <strong>Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.</strong> Am. J. Hum. Genet. 61: 40-50, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245983</a>] [<a href="https://doi.org/10.1086/513886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245983">Campbell et al. (1997)</a>, <a href="#16" class="mim-tip-reference" title="Burghes, A. H. M. <strong>When is a deletion not a deletion? When it is converted. (Editorial)</strong> Am. J. Hum. Genet. 61: 9-15, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245977</a>] [<a href="https://doi.org/10.1086/513913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245977">Burghes (1997)</a> raised the question of whether the centromeric SMN2 gene might be activated to compensate for the deficiency of SMN1 as a therapeutic strategy in SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9245983+9245977" 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="#83" class="mim-tip-reference" title="Samilchuk, E., D'Souza, B., Bastaki, L. <strong>Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy.</strong> Hum. Genet. 98: 524-527, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882869</a>] [<a href="https://doi.org/10.1007/s004390050253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8882869">Samilchuk et al. (1996)</a> carried out deletion analysis of the SMN and NAIP genes in 11 cases of type I SMA and 4 cases of type II SMA. The patients were of Kuwaiti origin. They also analyzed samples from 41 healthy relatives of these patients and 44 control individuals of Arab origin. They found homozygous deletions of exons 7 and 8 of the SMN gene in all SMA patients studied. Exon 5 of the NAIP gene was homozygously absent in all type I SMA patients, but was retained in the type II patients. Among relatives, they identified 1 mother was had homozygous deletion of NAIP. All of the control individuals had normal SMN and NAIP. <a href="#83" class="mim-tip-reference" title="Samilchuk, E., D'Souza, B., Bastaki, L. <strong>Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy.</strong> Hum. Genet. 98: 524-527, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882869</a>] [<a href="https://doi.org/10.1007/s004390050253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8882869">Samilchuk et al. (1996)</a> concluded that the incidence of NAIP deletion is much higher in the clinically more severe cases (type I SMA) than in the milder forms, and all of the type II SMA patients in their study had at least one copy of the intact NAIP gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8882869" 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="#86" class="mim-tip-reference" title="Somerville, M. J., Hunter, A. G. W., Aubry, H. L., Korneluk, R. G., MacKenzie, A. E., Surh, L. C. <strong>Clinical application of the molecular diagnosis of spinal muscular atrophy: deletions of neuronal apoptosis inhibitor protein and survival motor neuron genes.</strong> Am. J. Med. Genet. 69: 159-165, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9056553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9056553</a>]" pmid="9056553">Somerville et al. (1997)</a> presented a compilation of genotypes for the SMN1 and NAIP genes from their own laboratory and those of others as reported in the literature. Bayesian analyses were used to generate probabilities for SMA when deletions were present or absent in SMN1. They found that when the SMN1 exon 7 was deleted, the probability of SMA could reach greater than 98% in some populations, and when SMN1 was present, the probability of SMA was approximately 17 times less than the prior population risk. Deletion of NAIP exon 5, as well as SMN1 exon 7, was associated with a 5-fold increased risk of type I SMA. Case studies were used to illustrate differing disease risks for pre- and postnatal testing, depending on the presence of information about clinical status or molecular results. These analyses demonstrated that deletion screening of candidate genes can be a powerful tool in the diagnosis of SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9056553" 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="#74" class="mim-tip-reference" title="Novelli, G., Semprini, S., Capon, F., Dallapiccola, B. <strong>A possible role of NAIP gene deletions in sex-related spinal muscular atrophy phenotype variation.</strong> Neurogenetics 1: 29-30, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10735271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10735271</a>] [<a href="https://doi.org/10.1007/s100480050004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10735271">Novelli et al. (1997)</a> investigated the effects of gender on the association between NAIP gene deletion and disease severity in SMA. NAIP deletions were screened in 197 SMA patients lacking SMN; the results obtained were correlated with disease severity in male and female samples separately. No significant relationship between deletion size and clinical phenotype was observed among male patients, whereas in females the absence of NAIP was strongly associated with a severe phenotype (p less than 0.0001). SMA I was found in 75.6% of females and only 52.5% of males lacking NAIP. These results provided a possible molecular explanation for the sex-dependent phenotypic variation observed in SMA patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10735271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using comparative genomics to screen for modifying factors in SMA among sequences evolutionarily conserved between mouse and human, <a href="#84" class="mim-tip-reference" title="Scharf, J. M., Endrizzi, M. G., Wetter, A., Huang, S., Thompson, T. G., Zerres, K., Dietrich, W. F., Wirth, B., Kunkel, L. M. <strong>Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics.</strong> Nature Genet. 20: 83-86, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731538</a>] [<a href="https://doi.org/10.1038/1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731538">Scharf et al. (1998)</a> identified a novel transcript, H4F5 (<a href="/entry/603011">603011</a>), which lay closer to SMN1 than any previously identified gene in the region. They found that a multicopy microsatellite marker that was deleted in more than 90% of type I SMA chromosomes was embedded in an intron of the SMN1 gene, indicating that H4F5 may also be deleted in type I SMA, and thus was a candidate phenotypic modifier for SMA. In comparison with the high rate of H4F5 deletions in type I SMA, <a href="#84" class="mim-tip-reference" title="Scharf, J. M., Endrizzi, M. G., Wetter, A., Huang, S., Thompson, T. G., Zerres, K., Dietrich, W. F., Wirth, B., Kunkel, L. M. <strong>Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics.</strong> Nature Genet. 20: 83-86, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731538</a>] [<a href="https://doi.org/10.1038/1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731538">Scharf et al. (1998)</a> found that the deletion frequency in type II SMA chromosomes was between that of type I and control chromosomes, whereas the frequency in type III chromosomes was only slightly higher than in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731538" 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="#48" class="mim-tip-reference" title="Jedrzejowska, M., Borkowska, J., Zimowski, J., Kostera-Pruszczyk, A., Milewski, M., Jurek, M., Sielska, D., Kostyk, E., Nyka, W., Zaremba, J., Hausmanowa-Petrusewicz, I. <strong>Unaffected patients with a homozygous absence of the SMN1 gene.</strong> Europ. J. Hum. Genet. 16: 930-934, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337729</a>] [<a href="https://doi.org/10.1038/ejhg.2008.41" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337729">Jedrzejowska et al. (2008)</a> reported 3 unrelated families with asymptomatic carriers of a biallelic deletion of the SMN1 gene. In the first family, the biallelic deletion was found in 3 sibs: 2 affected brothers with SMA3 and a 25-year-old asymptomatic sister. All of them had 4 copies of the SMN2 gene. In the second family, 4 sibs were affected, 3 with SMA2 and 1 with SMA3, and each had 3 copies of SMN2. The clinically asymptomatic 47-year-old father had the biallelic deletion and 4 copies of SMN2. In the third family, the biallelic SMN1 deletion was found in a girl affected with SMA1 and in her healthy 53-year-old father who had 5 copies of SMN2. The findings again confirmed that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but also suggested that other factors play a role in disease modification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337729" 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="#81" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Berg, C., Zerres, K., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Heller, R. <strong>Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling.</strong> Clin. Genet. 76: 168-178, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19780763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19780763</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01200.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19780763">Rudnik-Schoneborn et al. (2009)</a> reviewed the clinical features of 66 German patients with SMA type 1 caused by homozygous deletion of the SMN1 gene. Reduced fetal movements were recorded in 33% of pregnancies. Sixteen (24%) patients showed onset of weakness in the first week of life; the overall mean age at death was 9 months. Four (6.1%) patients with 1 SMN2 gene copy had severe SMA type '0' with joint contractures and respiratory distress from birth. All died within a few months of age. Among the 57 (86.3%) patients with 2 SMN2 copies, the mean age at onset was 1.3 months, and the mean age at disease endpoint (death or need for permanent ventilation) was 7.8 months. Among the 5 (7.6%) of patients with 3 SMN2 copies, the mean age at onset was 3.4 months and the mean age at endpoint was 28.9 months (range, 10 to 55 months). <a href="#81" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Berg, C., Zerres, K., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Heller, R. <strong>Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling.</strong> Clin. Genet. 76: 168-178, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19780763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19780763</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01200.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19780763">Rudnik-Schoneborn et al. (2009)</a> noted that much of the observed clinical variability in SMA type 1 likely depends on the number of SMN2 copies, and suggested that the SMN2 copy number should be considered in clinical trials. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19780763" 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="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#26" class="mim-tip-reference" title="Czeizel, A., Hamula, J. <strong>A Hungarian study on Werdnig-Hoffmann disease.</strong> J. Med. Genet. 26: 761-763, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2614795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2614795</a>] [<a href="https://doi.org/10.1136/jmg.26.12.761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2614795">Czeizel and Hamula (1989)</a> and <a href="#27" class="mim-tip-reference" title="Czeizel, A. <strong>High incidence of acute infantile spinal atrophy in Hungary. (Letter)</strong> Hum. Genet. 86: 539, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2016096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2016096</a>] [<a href="https://doi.org/10.1007/BF00194653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2016096">Czeizel (1991)</a> estimated the prevalence of Werdnig-Hoffmann disease in Hungary to be 1 per 10,000 live births. The occurrence in sibs was 32%, a figure considered consistent with autosomal recessive inheritance complicated by greater ascertainment of families with more than 1 affected child. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2614795+2016096" 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>From an epidemiologic study of acute and chronic childhood SMA in Poland, <a href="#88" class="mim-tip-reference" title="Spiegler, A. W. J., Hausmanowa-Petrusewicz, I., Borkowska, J., Klopocka, A. <strong>Population data on acute infantile and chronic childhood spinal muscular atrophy in Warsaw.</strong> Hum. Genet. 85: 211-214, 1990."None>Spiegler et al. (1990)</a> cited a frequency of 1.026 cases per 10,000, a gene frequency of 0.01428, and a carrier frequency of 1 in 35. <a href="#88" class="mim-tip-reference" title="Spiegler, A. W. J., Hausmanowa-Petrusewicz, I., Borkowska, J., Klopocka, A. <strong>Population data on acute infantile and chronic childhood spinal muscular atrophy in Warsaw.</strong> Hum. Genet. 85: 211-214, 1990."None>Spiegler et al. (1990)</a> reviewed various other reports on the frequency of SMA. For an 8-year period (1980-1987) in the State of North Dakota, <a href="#15" class="mim-tip-reference" title="Burd, L., Short, S. K., Martsolf, J. T., Nelson, R. A. <strong>Prevalence of type I spinal muscular atrophy in North Dakota.</strong> Am. J. Med. Genet. 41: 212-215, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1785637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1785637</a>] [<a href="https://doi.org/10.1002/ajmg.1320410216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1785637">Burd et al. (1991)</a> found an incidence of 1 in 6,720 births (14 in 94,092). In an Italian population, <a href="#69" class="mim-tip-reference" title="Mostacciuolo, M. L., Danieli, G. A., Trevisan, C., Muller, E., Angelini, C. <strong>Epidemiology of spinal muscular atrophies in a sample of the Italian population.</strong> Neuroepidemiology 11: 34-38, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1608493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1608493</a>] [<a href="https://doi.org/10.1159/000110905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1608493">Mostacciuolo et al. (1992)</a> found an overall prevalence at birth for SMA types I, II, and III to be 7.8 in 100,000 live births. Type I alone accounted for 4.1 in 100,000 live births. Assuming that the 3 types are clinical manifestations of allelic mutations, the locus mutation rate would be about 70 x 10(-6) and the frequency of heterozygotes about 1 in 57. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1608493+1785637" 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="#94" class="mim-tip-reference" title="Wilmshurst, J. M., Reynolds, L., Van Toorn, R., Leisegang, F., Henderson, H. E. <strong>Spinal muscular atrophy in black South Africans: concordance with the universal SMN1 genotype.</strong> Clin. Genet. 62: 165-168, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220455</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620210.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12220455">Wilmshurst et al. (2002)</a> performed DNA studies in 30 unrelated and racially diverse patients with SMA residing in the Western Cape of South Africa. Four had SMA type I, 16 had type II, and 10 had type III. All patients were found to be homozygous for the loss of either exon 7 or exons 7 and 8 of the SMN1 gene. Thus, all patients from the Western Cape, which included 12 black South Africans, were no different genetically or phenotypically from the internationally recognized form of typical SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220455" 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="#103" class="mim-tip-reference" title="Zaldivar, T., Montejo, Y., Acevedo, A. M., Guerra, R., Vargas, J., Garofalo, N., Alvarez, R., Alvarez, M. A., Hardiman, O. <strong>Evidence of reduced frequency of spinal muscular atrophy type I in the Cuban population.</strong> Neurology 65: 636-638, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116135</a>] [<a href="https://doi.org/10.1212/01.wnl.0000172860.41953.12" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116135">Zaldivar et al. (2005)</a> found that the incidence of SMA type I in Cuba was 3.53 per 100,000 live births. When the population was classified according to self-reported ethnicity, the incidence was 8 per 100,000 for whites, 0.89 per 100,000 for blacks, and 0.96 per 100,000 for those of mixed ethnicity. <a href="#103" class="mim-tip-reference" title="Zaldivar, T., Montejo, Y., Acevedo, A. M., Guerra, R., Vargas, J., Garofalo, N., Alvarez, R., Alvarez, M. A., Hardiman, O. <strong>Evidence of reduced frequency of spinal muscular atrophy type I in the Cuban population.</strong> Neurology 65: 636-638, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116135</a>] [<a href="https://doi.org/10.1212/01.wnl.0000172860.41953.12" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116135">Zaldivar et al. (2005)</a> concluded that SMA I may occur less frequently in those of African ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a detailed review, <a href="#59" class="mim-tip-reference" title="Lunn, M. R., Wang, C. H. <strong>Spinal muscular atrophy.</strong> Lancet 371: 2120-2133, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18572081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18572081</a>] [<a href="https://doi.org/10.1016/S0140-6736(08)60921-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18572081">Lunn and Wang (2008)</a> stated that the incidence of SMA was 1 in 10,000 livebirths and that the carrier frequency was 1 in 50. In a reply, <a href="#95" class="mim-tip-reference" title="Wilson, R. B., Ogino, S. <strong>Carrier frequency of spinal muscular atrophy. (Letter)</strong> Lancet 372: 1542 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18984183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18984183</a>] [<a href="https://doi.org/10.1016/S0140-6736(08)61645-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18984183">Wilson and Ogino (2008)</a> stated that carrier testing had revealed a carried frequency of 1 in 38, which extrapolates to an incidence of 1 in 6,000 livebirths under Hardy-Weinberg equilibrium. <a href="#95" class="mim-tip-reference" title="Wilson, R. B., Ogino, S. <strong>Carrier frequency of spinal muscular atrophy. (Letter)</strong> Lancet 372: 1542 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18984183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18984183</a>] [<a href="https://doi.org/10.1016/S0140-6736(08)61645-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18984183">Wilson and Ogino (2008)</a> postulated that the numerical differences could be due to embryonic lethality or clinically atypical SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18984183+18572081" 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="#44" class="mim-tip-reference" title="Hendrickson, B. C., Donohoe, C., Akmaev, V. R., Sugarman, E. A., Labrousse, P., Boguslavskiy, L., Flynn, K., Rohlfs, E. M., Walker, A., Allitto, B., Sears, C., Scholl, T. <strong>Differences in SMN1 allele frequencies among ethnic groups within North America. (Letter)</strong> J. Med. Genet. 46: 641-644, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19625283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19625283</a>] [<a href="https://doi.org/10.1136/jmg.2009.066969" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19625283">Hendrickson et al. (2009)</a> genotyped more than 1,000 specimens from various ethnic groups using a quantitative real-time PCR assay specific for the 840C-T change in exon 7, which results in loss of SMN1. The observed 1-copy SMN1 carrier rate was 1 in 37 (2.7%) among Caucasians, 1 in 46 (2.2%) among Ashkenazi Jews, 1 in 56 (1.8%) 56 among Asians, 1 in 91 (1.1%) among African Americans, and 1 in 125 (0.8%) among Hispanics. In all groups except African Americans the 2-copy genotype was the most common. However, African American specimens had an unusually high frequency of alleles with multiple copies of SMN1 (27% compared to 3.3-8.1%). The authors noted that alleles with increased numbers of SMN1 copies increase the relative risk of being a carrier due to the inability of many methods to detect the rare SMN1 genotype consisting of 1 allele with zero copies and the other allele with 2 or more copies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19625283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using denaturing high-performance liquid chromatography (DHPLC) as a screening tool to determine SMN copy number, <a href="#85" class="mim-tip-reference" title="Sheng-Yuan, Z., Xiong, F., Chen, Y.-J., Yan, T.-Z., Zeng, J., Li, L., Zhang, Y.-N., Chen, W.-Q., Bao, X.-H., Zhang, C., Xu, X.-M. <strong>Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.</strong> Europ. J. Hum. Genet. 18: 978-984, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20442745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20442745</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20442745[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/ejhg.2010.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20442745">Sheng-Yuan et al. (2010)</a> found a heterozygous deletion of SMN1 exon 7 in 41 (2.39%) of 1,712 cord blood samples from Chinese infants, indicating a carrier state. Thirteen different genotypic groups characterized by SMN1:SMN2 copy number ratio were identified overall. Carrier genotypes were similar among 25 core families with the disorder, with the '1+0' SMN1 genotype accounting for 90.9% of carriers, although 2 of 44 parents had the rare '2+0' genotype. <a href="#85" class="mim-tip-reference" title="Sheng-Yuan, Z., Xiong, F., Chen, Y.-J., Yan, T.-Z., Zeng, J., Li, L., Zhang, Y.-N., Chen, W.-Q., Bao, X.-H., Zhang, C., Xu, X.-M. <strong>Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.</strong> Europ. J. Hum. Genet. 18: 978-984, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20442745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20442745</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20442745[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/ejhg.2010.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20442745">Sheng-Yuan et al. (2010)</a> developed an assay based on reverse dot blot for rapid genotyping of exon 7 deletional SMA. <a href="#85" class="mim-tip-reference" title="Sheng-Yuan, Z., Xiong, F., Chen, Y.-J., Yan, T.-Z., Zeng, J., Li, L., Zhang, Y.-N., Chen, W.-Q., Bao, X.-H., Zhang, C., Xu, X.-M. <strong>Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.</strong> Europ. J. Hum. Genet. 18: 978-984, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20442745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20442745</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20442745[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/ejhg.2010.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20442745">Sheng-Yuan et al. (2010)</a> concluded that the carrier rate of SMA in China is 1 in 42 and that approximately 2,306 newborns are affected each year. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20442745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Chong, J. X., Oktay, A. A., Dai, Z., Swoboda, K .J., Prior, T. W., Ober, C. <strong>A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites.</strong> Europ. J. Hum. Genet. 19: 1045-1051, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21610747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21610747</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21610747[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/ejhg.2011.85" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21610747">Chong et al. (2011)</a> identified a shared haplotype encompassing the SMN1/SMN2 genes in a Hutterite patient from South Dakota and 3 Hutterite patients from Montana. An 8-generation pedigree connected these 4 individuals to their most recent common ancestors, who were a couple born in the 1790s. All 4 patients carried zero copies of SMN1 and 4 copies of SMN2, indicating that the haplotype carrying the deletion of SMN1 also carries 2 copies of SMN2. The carrier frequency for this haplotype was 12.9% in South Dakota Hutterites. The phenotypic expression of this phenotype was relatively mild, and 1 asymptomatic homozygous adult was identified. <a href="#22" class="mim-tip-reference" title="Chong, J. X., Oktay, A. A., Dai, Z., Swoboda, K .J., Prior, T. W., Ober, C. <strong>A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites.</strong> Europ. J. Hum. Genet. 19: 1045-1051, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21610747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21610747</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21610747[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/ejhg.2011.85" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21610747">Chong et al. (2011)</a> identified a 26-SNP haplotype that could be used for screening in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21610747" 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>Among 23,127 ethnically diverse individuals screened for SMA1 carrier status, <a href="#53" class="mim-tip-reference" title="Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S. <strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong> Genet. Med. 15: 178-186, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22975760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22975760</a>] [<a href="https://doi.org/10.1038/gim.2012.114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22975760">Lazarin et al. (2013)</a> identified 405 carriers (1.8%), for an estimated carrier frequency of approximately 1 in 57. Fifteen 'carrier couples' were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22975760" 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="#5" class="mim-tip-reference" title="Becker, P. E. <strong>Atrophia musculorum spinalis pseudomyopathica. Hereditaere neurogene proximale Amyotrophie von Kugelberg und Welander.</strong> Z. Menschl. Vererb. Konstitutionsl. 37: 193-220, 1964."None>Becker (1964)</a> suggested an allelic model for the clinically distinct subtypes of SMA: 3 or more normal alleles (a, a', a'') in addition to the pathologic gene a(+). The genotype a'a(+) was thought to lead to Kugelberg-Welander phenotype and the a''a(+) genotype to the Werdnig-Hoffmann phenotype. <a href="#8" class="mim-tip-reference" title="Bouwsma, G., Leschot, N. J. <strong>Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis.</strong> Clin. Genet. 30: 145-149, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3780029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3780029</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1986.tb00586.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3780029">Bouwsma and Leschot (1986)</a> extended the allele hypothesis of Becker. They presented clinical and genetic findings in 18 patients from 7 pedigrees showing an unusual genetic pattern not consistent with simple autosomal recessive inheritance. In 6 of the 7 pedigrees, different types of SMA were present. However, <a href="#70" class="mim-tip-reference" title="Muller, B., Melki, J., Burlet, P., Clerget-Darpoux, F. <strong>Proximal spinal muscular atrophy (SMA) types II and III in the same sibship are not caused by different alleles at the SMA locus on 5q.</strong> Am. J. Hum. Genet. 50: 892-895, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1570842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1570842</a>]" pmid="1570842">Muller et al. (1992)</a> presented evidence rejecting the Becker hypothesis. In a sample of 4 sibships in which both SMA type II and SMA type III occurred, the segregation of linked markers indicated that the same allele was involved. The finding suggested that other factors, genetic or environmental, must determine disease severity in SMA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3780029+1570842" 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="#51" class="mim-tip-reference" title="Kleyn, P. W., Brzustowicz, L. M., Wilhelmsen, K. C., Freimer, N. B., Miller, J. M., Munsat, T. L., Gilliam, T. C. <strong>Spinal muscular atrophy is not the result of mutations at the beta-hexosaminidase or GM(2)-activator locus.</strong> Neurology 41: 1418-1422, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1679910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1679910</a>] [<a href="https://doi.org/10.1212/wnl.41.9.1418" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1679910">Kleyn et al. (1991)</a> excluded both the HEXB locus (<a href="/entry/606873">606873</a>) and the GM2-activator protein locus (GM2A; <a href="/entry/613109">613109</a>), both of which are located on chromosome 5, as the site of the mutation in SMA. Recombination between HEXB and SMA eliminated this enzyme as a candidate site. Furthermore, the gene encoding the activator protein was found to map distal to the SMA I locus (<a href="#45" class="mim-tip-reference" title="Heng, H. H. Q., Xie, B., Shi, X.-M., Tsui, L.-C., Mahuran, D. J. <strong>Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus.</strong> Genomics 18: 429-431, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8288250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8288250</a>] [<a href="https://doi.org/10.1006/geno.1993.1491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8288250">Heng et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1679910+8288250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Exclusion of the Wobbler Mouse and a Canine Model</em></strong></p><p>
|
|
<a href="#50" class="mim-tip-reference" title="Kaupmann, K., Simon-Chazottes, D., Guenet, J.-L., Jockusch, H. <strong>Wobbler, a mutation affecting motoneuron survival and gonadal functions in the mouse, maps to proximal chromosome 11.</strong> Genomics 13: 39-43, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349581</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90199-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349581">Kaupmann et al. (1992)</a> mapped the 'wobbler' locus (wr) (see <a href="/entry/614633">614633</a>) to proximal mouse chromosome 11. The wobbler mouse (genotype wr/wr) shows motoneuron disease and gonadal dysfunction. <a href="#50" class="mim-tip-reference" title="Kaupmann, K., Simon-Chazottes, D., Guenet, J.-L., Jockusch, H. <strong>Wobbler, a mutation affecting motoneuron survival and gonadal functions in the mouse, maps to proximal chromosome 11.</strong> Genomics 13: 39-43, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349581</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90199-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349581">Kaupmann et al. (1992)</a> stated that the wobbler was an unlikely model for human SMA because it shows also a striking spermiogenesis defect which has not been reported for male SMA patients who have reached adolescence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1349581" 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="#30" class="mim-tip-reference" title="des Portes, V., Coulpier, M., Melki, J., Dreyfus, P. A. <strong>Early detection of mouse wobbler mutation: a model of pathological motoneurone death.</strong> Neuroreport 5: 1861-1864, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7841363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7841363</a>] [<a href="https://doi.org/10.1097/00001756-199410000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7841363">Des Portes et al. (1994)</a> also mapped the mouse 'wobbler' mutation to mouse chromosome 11, about 1 cM from the glutamine synthetase gene (<a href="/entry/138290">138290</a>); several crossovers excluded glutamine synthetase from being a candidate gene for the wobbler mutation. The murine equivalent of the human 5q region is mainly situated on chromosomes 13 and 11, and the closest published marker for human spinal muscular atrophy, D5S39, was mapped to mouse chromosome 13. Thus, it seemed unlikely that the wobbler mutation and the common human spinal muscular atrophies were genetically identical, despite their similar phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7841363" 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="Blazej, R. G., Mellersh, C. S., Cork, L. C., Ostrander, E. A. <strong>Hereditary canine spinal muscular atrophy is phenotypically similar but molecularly distinct from human spinal muscular atrophy.</strong> J. Hered. 89: 531-537, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9864863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9864863</a>] [<a href="https://doi.org/10.1093/jhered/89.6.531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9864863">Blazej et al. (1998)</a> concluded that autosomal dominant canine spinal muscular atrophy, which has pathologic and clinical features similar to various forms of human motor neuron disease, was molecularly distinct from human spinal muscular atrophy. They studied the canine SMN gene in affected and unaffected dogs and found no germline mutations in the SMN gene in affected dogs. Analysis of a panel of canine/rodent hybrid cell lines revealed that the SMN gene did not map to the same chromosome in the dog as did the canine spinal muscular atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9864863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Other Animal Models</em></strong></p><p>
|
|
<a href="#47" class="mim-tip-reference" title="Hsieh-Li, H. M., Chang, J.-G., Jong, Y.-J., Wu, M.-H., Wang, N. M., Tsai, C. H., Li, H. <strong>A mouse model for spinal muscular atrophy.</strong> Nature Genet. 24: 66-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615130</a>] [<a href="https://doi.org/10.1038/71709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615130">Hsieh-Li et al. (2000)</a> produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2 (<a href="/entry/601627">601627</a>). Smn -/- mice died during the periimplantation stage. In contrast, transgenic mice harboring SMN2 in the Smn -/- background showed pathologic changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathologic changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. The results demonstrated that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn -/- SMN2 mice reflected those seen in SMA patients, thus providing a mouse model for that disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10615130" 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="#34" class="mim-tip-reference" title="Frugier, T., Tiziano, F. D., Cifuentes-Diaz, C., Miniou, P., Roblot, N., Dierich, A., Le Meur, M., Melki, J. <strong>Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy.</strong> Hum. Molec. Genet. 9: 849-858, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749994</a>] [<a href="https://doi.org/10.1093/hmg/9.5.849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10749994">Frugier et al. (2000)</a> used the Cre/loxP recombination system and a neuron-specific promoter to generate transgenic mice with selective expression in neural tissue of an SMN construct missing exon 7. Unlike mice missing SMN exon 7 in all tissues (an embryonic lethal phenotype), those with a neuron-specific defect displayed a severe motor deficit with tremors. The mutated SMN protein lacked the normal C terminus and was dramatically reduced in motor neuron nuclei. Histologic analysis revealed a lack of GEMS (gemini of coiled bodies, which are normal nuclear structures) and the presence of large aggregates of coilin, a coiled body-specific protein (<a href="/entry/600272">600272</a>). The authors concluded that the lack of nuclear targeting of SMN is the biochemical defect in SMA, which leads to muscle denervation of neurogenic origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749994" 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>Studying Brown-Swiss cattle, <a href="#64" class="mim-tip-reference" title="Medugorac, I., Kemter, J., Russ, I., Pietrowski, D., Nuske, S., Reichenbach, H.-D., Schmahl, W., Forster, M. <strong>Mapping of the bovine spinal muscular atrophy locus to chromosome 24.</strong> Mammalian Genome 14: 383-391, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12879360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12879360</a>] [<a href="https://doi.org/10.1007/s00335-002-3024-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12879360">Medugorac et al. (2003)</a> mapped the bovine spinal muscular atrophy locus to chromosome 24. Before performing a genomewide linkage analysis, they investigated 2 candidate chromosome segments: the proximal part of bovine chromosome 20 and the complete bovine chromosome 29. These regions are orthologous to human chromosome segments responsible for SMA1 and SMA with respiratory distress (SMARD1; <a href="/entry/604320">604320</a>), respectively. No abnormalities were found in these regions. The linkage region on chromosome 24 contains the homolog of the BCL2 gene (<a href="/entry/151430">151430</a>) on human chromosome 18q. <a href="#64" class="mim-tip-reference" title="Medugorac, I., Kemter, J., Russ, I., Pietrowski, D., Nuske, S., Reichenbach, H.-D., Schmahl, W., Forster, M. <strong>Mapping of the bovine spinal muscular atrophy locus to chromosome 24.</strong> Mammalian Genome 14: 383-391, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12879360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12879360</a>] [<a href="https://doi.org/10.1007/s00335-002-3024-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12879360">Medugorac et al. (2003)</a> suggested that the gene encoding the apoptosis-inhibiting protein BCL2 is a promising candidate for bovine SMA and that the disorder in Brown-Swiss cattle offers an attractive animal model for a better understanding of human SMA and for a probable antiapoptotic synergy of SMN-BCL2 aggregates in mammals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12879360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Chan, Y. B., Miguel-Aliaga, I., Franks, C., Thomas, N., Trulzsch, B., Sattelle, D. B., Davies, K. E., van den Heuvel, M. <strong>Neuromuscular defects in a Drosophila survival motor neuron gene mutant.</strong> Hum. Molec. Genet. 12: 1367-1376, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12783845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12783845</a>] [<a href="https://doi.org/10.1093/hmg/ddg157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12783845">Chan et al. (2003)</a> isolated a Drosophila smn mutant with point mutations in the smn gene similar to those found in SMA patients. Zygotic smn mutant animals showed abnormal motor behavior; smn gene activity was required in both neurons and muscle to alleviate this phenotype. Excitatory postsynaptic currents were reduced while synaptic motor neuron boutons were disorganized in mutants, indicating defects at the neuromuscular junction. Clustering of a neurotransmitter receptor subunit in the muscle at the neuromuscular junction was also severely reduced. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12783845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a mouse model of SMA, <a href="#49" class="mim-tip-reference" title="Kariya, S., Park, G.-H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M. S., Landmesser, L. T., Monani, U. R. <strong>Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.</strong> Hum. Molec. Genet. 17: 2552-2569, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492800</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492800[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18492800">Kariya et al. (2008)</a> demonstrated that the earliest structural defects of the disorder appeared in the distal muscles and involved the neuromuscular synapse even before the appearance of overt symptoms. Insufficient SMN protein arrested the postnatal development of the neuromuscular junction (NMJ), impairing the maturation of postsynaptic acetylcholine receptor (AChR) clusters. Presynaptic defects at the distal ends of alpha-motor neurons included poor terminal arborization, intermediate filament aggregates, and misplaced synaptic vesicles. These defects were reflected in functional deficits at the NMJ characterized by intermittent neurotransmission failures. <a href="#49" class="mim-tip-reference" title="Kariya, S., Park, G.-H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M. S., Landmesser, L. T., Monani, U. R. <strong>Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.</strong> Hum. Molec. Genet. 17: 2552-2569, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492800</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492800[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18492800">Kariya et al. (2008)</a> suggested that SMA might best be described as a NMJ synaptopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18492800" 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 severe SMA mice (Smn -/-;SMN2 +/+) <a href="#36" class="mim-tip-reference" title="Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U. R., Morris, G. E., Burghes, A. H. M. <strong>Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect.</strong> Hum. Molec. Genet. 17: 1063-1075, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178576</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18178576[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddm379" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18178576">Gavrilina et al. (2008)</a> found that transgenic embryonic expression of full-length SMN under the prion (<a href="/entry/176640">176640</a>) promoter in brain and spinal cord neurons rescued the phenotype. Mice homozygous for the transgene survived for an average of 210 days, compared to 4.6 days in control SMA mice, and lumbar motor neuron root counts in the transgenic mice were normal. High levels of SMN in neurons were observed at embryonic day 15. In contrast, transgenic expression of SMN solely in skeletal muscle using the human skeletal actin promoter resulted in no improvement of the SMA phenotype or extension of survival in SMA mice. However, 1 transgenic strain with high SMN expression in muscle and low SMN expression in brain showed increased survival to 160 days, indicating that even mild neuronal SMN expression can affect the phenotype. <a href="#36" class="mim-tip-reference" title="Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U. R., Morris, G. E., Burghes, A. H. M. <strong>Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect.</strong> Hum. Molec. Genet. 17: 1063-1075, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178576</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18178576[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddm379" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18178576">Gavrilina et al. (2008)</a> concluded that expression of full-length SMN in neurons can correct the severe SMA phenotype in mice, whereas high SMN levels in mature skeletal muscle alone has no impact. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18178576" 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="#71" class="mim-tip-reference" title="Murray, L. M., Lee, S., Baumer, D., Parson, S. H., Talbot, K., Gillingwater, T. H. <strong>Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy.</strong> Hum. Molec. Genet. 19: 420-433, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19884170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19884170</a>] [<a href="https://doi.org/10.1093/hmg/ddp506" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19884170">Murray et al. (2010)</a> investigated the presymptomatic development of neuromuscular connectivity in differentially vulnerable motor neuron populations in Smn -/-;SMN2 +/+ mice. Reduced Smn levels had no detectable effect on morphologic correlates of presymptomatic development in either vulnerable or stable motor units, indicating that abnormal presymptomatic developmental processes were unlikely to be a prerequisite for subsequent pathologic changes to occur in vivo. Microarray analyses of spinal cord from 2 different severe SMA mouse models demonstrated that only minimal changes in gene expression were present in presymptomatic mice. In contrast, microarray analysis of late-symptomatic spinal cord revealed widespread changes in gene expression, implicating extracellular matrix integrity, growth factor signaling, and myelination pathways in SMA pathogenesis. <a href="#71" class="mim-tip-reference" title="Murray, L. M., Lee, S., Baumer, D., Parson, S. H., Talbot, K., Gillingwater, T. H. <strong>Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy.</strong> Hum. Molec. Genet. 19: 420-433, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19884170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19884170</a>] [<a href="https://doi.org/10.1093/hmg/ddp506" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19884170">Murray et al. (2010)</a> suggested that reduced Smn levels induce SMA pathology by instigating rapidly progressive neurodegenerative pathways in lower motor neurons around the time of disease onset, rather than by modulating presymptomatic neurodevelopmental pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19884170" 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="#100" class="mim-tip-reference" title="Wishart, T. M., Huang, J. P.-W., Murray, L. M., Lamont, D. J., Mutsaers, C. A., Ross, J., Geldsetzer, P., Ansorge, O., Talbot, K., Parson, S. H., Gillingwater, T. H. <strong>SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy.</strong> Hum. Molec. Genet. 19: 4216-4228, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20705736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20705736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20705736[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20705736">Wishart et al. (2010)</a> showed that reduced levels of Smn led to impaired perinatal brain development in a mouse model of severe SMA. Regionally selective changes in brain morphology were apparent in areas normally associated with higher Smn levels in the healthy postnatal brain, including the hippocampus, and were associated with decreased cell density, reduced cell proliferation, and impaired hippocampal neurogenesis. A comparative proteomics analysis of the hippocampus from SMA and wildtype littermate mice revealed widespread modifications in expression levels of proteins regulating cellular proliferation, migration, and development when Smn levels were reduced. <a href="#100" class="mim-tip-reference" title="Wishart, T. M., Huang, J. P.-W., Murray, L. M., Lamont, D. J., Mutsaers, C. A., Ross, J., Geldsetzer, P., Ansorge, O., Talbot, K., Parson, S. H., Gillingwater, T. H. <strong>SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy.</strong> Hum. Molec. Genet. 19: 4216-4228, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20705736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20705736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20705736[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20705736">Wishart et al. (2010)</a> proposed roles for SMN protein in brain development and maintenance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20705736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Therapeutic Strategies</em></strong></p><p>
|
|
In SMA-like mouse embryonic fibroblasts and human SMN2-transfected motor neuron cells, <a href="#92" class="mim-tip-reference" title="Ting, C.-H., Lin, C.-W., Wen, S.-L., Hsieh-Li, H.-M., Li, H. <strong>Stat5 constitutive activation rescues defects in spinal muscular atrophy.</strong> Hum. Molec. Genet. 16: 499-514, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17220171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17220171</a>] [<a href="https://doi.org/10.1093/hmg/ddl482" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17220171">Ting et al. (2007)</a> found that sodium vanadate, trichostatin A, and aclarubicin effectively enhanced SMN2 expression by inducing Stat5 (<a href="/entry/601511">601511</a>) activation. This resulted in enhanced SMN2 promoter activity with an increase in both full-length and deletion exon 7 SMN transcripts in human cells with SMN2. Knockdown of Stat5 expression disrupted the effects of sodium vanadate on SMN2 activation, but did not influence SMN2 splicing, suggesting that Stat5 signaling is involved in SMN2 transcriptional regulation. Constitutive expression of the activated Stat5 mutant Stat5A1*6 profoundly increased the number of nuclear gems in SMA patient lymphocytes and reduced SMA-like motor neuron axon outgrowth defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17220171" 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="#72" class="mim-tip-reference" title="Narver, H. L., Kong, L., Burnett, B. G., Choe, D. W., Bosch-Marce, M., Taye, A. A., Eckhaus, M. A., Sumner, C. J. <strong>Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition.</strong> Ann. Neurol. 64: 465-470, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18661558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18661558</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18661558[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18661558">Narver et al. (2008)</a> found that in a transgenic mouse model of SMA (Smn +/-, SMN2 +/+, SMN-delta-7) early treatment with the HDAC (<a href="/entry/601241">601241</a>) inhibitor, trichostatin A (TSA), plus nutritional support extended median survival by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after TSA was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe SMA. <a href="#72" class="mim-tip-reference" title="Narver, H. L., Kong, L., Burnett, B. G., Choe, D. W., Bosch-Marce, M., Taye, A. A., Eckhaus, M. A., Sumner, C. J. <strong>Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition.</strong> Ann. Neurol. 64: 465-470, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18661558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18661558</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18661558[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18661558">Narver et al. (2008)</a> concluded that early SMA disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of HDAC inhibitor treatment in human patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18661558" 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="#68" class="mim-tip-reference" title="Meyer, K., Marquis, J., Trub, J., Nlend Nlend, R., Verp, S., Ruepp, M.-D., Imboden, H., Barde, I., Trono, D., Schumperli, D. <strong>Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation.</strong> Hum. Molec. Genet. 18: 546-555, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19010792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19010792</a>] [<a href="https://doi.org/10.1093/hmg/ddn382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19010792">Meyer et al. (2009)</a> created an optimal exon 7 inclusion strategy based on a bifunctional U7 snRNA (RNU7-1; <a href="/entry/617876">617876</a>) construct that targets the 3-prime part of exon 7 and carries an ESE sequence that can attract stimulatory splice factors. This construct induced nearly complete exon 7 inclusion of an SMN2-reporter in HeLa cells and of endogenous SMN2 in SMA type I patient fibroblasts. Introduction of the U7-ESE-B construct in a severe mouse model of SMA resulted in a clear suppression of disease-associated symptoms, ranging from normal life span with pronounced SMA symptoms to full weight development, muscular function, and ability of female mice to carry to term and feed a normal-sized litter. Exon 7 inclusion in total spinal RNA increased from 26% to 52%, and SMN protein levels increased, albeit only to levels one-fifth of that seen wildtype mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19010792" 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="#101" class="mim-tip-reference" title="Workman, E., Saieva, L., Carrel, T. L., Crawford, T. O., Liu, D., Lutz, C., Beattie, C. E., Pellizzoni, L., Burghes, A. H. M. <strong>A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice.</strong> Hum. Molec. Genet. 18: 2215-2229, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329542</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329542[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19329542">Workman et al. (2009)</a> showed that SMN(A111G), an allele capable of snRNP assembly (A111G; <a href="/entry/600354#0015">600354.0015</a>), can rescue mice that lacked Smn and contained either 1 or 2 copies of SMN2 (SMA mice). The correction of SMA in these animals was directly correlated with snRNP assembly activity in spinal cord, as was correction of snRNA levels. These data support snRNP assembly as being the critical function affected in SMA and suggests that the levels of snRNPs are critical to motor neurons. Furthermore, SMN(A111G) could not rescue Smn-null mice without SMN2, suggesting that both SMN(A111G) and SMN from SMN2 may undergo intragenic complementation in vivo to function in heteromeric complexes that have greater function than either allele alone. The oligomer composed of limiting full-length SMN and SMN(A111G) had substantial snRNP assembly activity. The SMN(A2G) (A2G; <a href="/entry/600354#0002">600354.0002</a>) and SMN(A111G) alleles in vivo did not complement each other, leading to the possibility that these mutations could affect the same function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19329542" 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="#63" class="mim-tip-reference" title="Mattis, V. B., Ebert, A. D., Fosso, M. Y., Chang, C.-W., Lorson, C. L. <strong>Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model.</strong> Hum. Molec. Genet. 18: 3906-3913, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19625298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19625298</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19625298[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19625298">Mattis et al. (2009)</a> examined the potential therapeutic capabilities of a novel aminoglycoside, TC007. In an intermediate SMA mouse model (Smn -/-; SMN2 +/+; SMN-delta-7), when delivered directly to the central nervous system, TC007 induced SMN in both the brain and spinal cord, significantly increased life span (approximately 30%), and increased ventral horn cell number, consistent with its ability to increase SMN levels in induced pluripotent stem cell-derived human SMA motor neuron cultures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19625298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Butchbach, M. E. R., Singh, J., Porsteinsdottir, M., Saieva, L., Slominski, E., Thurmond, J., Andresson, T., Zhang, J., Edwards, J. D., Simard, L. R., Pellizzoni, L., Jarecki, J., Burghes, A. H. M., Gurney, M. E. <strong>Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy.</strong> Hum. Molec. Genet. 19: 454-467, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19897588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19897588</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19897588[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp510" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19897588">Butchbach et al. (2010)</a> tested a series of C5-quinazoline derivatives for their ability to increase SMN expression in vivo. Oral administration of 3 compounds (D152344, D153249, and D156844) to neonatal SMN-delta-7 mice resulted in a dose-dependent increase in Smn promoter activity in the central nervous system. Oral administration of D156844 significantly increased the mean life span of SMN-delta-7 SMA mice by approximately 20-30% when given prior to motor neuron loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19897588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Bowerman, M., Beauvais, A., Anderson, C. L., Kothary, R. <strong>Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model.</strong> Hum. Molec. Genet. 19: 1468-1478, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097679</a>] [<a href="https://doi.org/10.1093/hmg/ddq021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20097679">Bowerman et al. (2010)</a> showed that Smn depletion led to increased activation of RhoA (<a href="/entry/165390">165390</a>), a major regulator of actin dynamics, in the spinal cord of an intermediate SMA mouse model. Treating these mice with Y-27632, which inhibits ROCK (<a href="/entry/601702">601702</a>), a direct downstream effector of RhoA, dramatically improved their survival. This life span rescue was independent of Smn expression and was accompanied by an improvement in the maturation of the neuromuscular junctions and an increase in muscle fiber size in the SMA mice. <a href="#9" class="mim-tip-reference" title="Bowerman, M., Beauvais, A., Anderson, C. L., Kothary, R. <strong>Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model.</strong> Hum. Molec. Genet. 19: 1468-1478, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097679</a>] [<a href="https://doi.org/10.1093/hmg/ddq021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20097679">Bowerman et al. (2010)</a> proposed a role for disruption of actin cytoskeletal dynamics to SMA pathogenesis and suggested that RhoA effectors may be viable targets for therapeutic intervention in the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20097679" 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="#1" class="mim-tip-reference" title="Ackermann, B., Krober, S., Torres-Benito, L., Borgmann, A., Peters, M., Barkooie, S. M. H., Tejero, R., Jakubik, M., Schreml, J., Milbradt, J., Wunderlich, T. F., Riessland, M., Tabares, L., Wirth, B. <strong>Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality.</strong> Hum. Molec. Genet. 22: 1328-1347, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23263861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23263861</a>] [<a href="https://doi.org/10.1093/hmg/dds540" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23263861">Ackermann et al. (2013)</a> found that ubiquitous overexpression of human PLS3 (<a href="/entry/300131">300131</a>) in mice with a mild SMA phenotype improved motor ability and neuromuscular junction function and moderately increased survival compared with control SMA mice. Expression of PLS3 did not improve the morphology of heart, lung, or intestine, and it did not improve motor ability or survival in mice with a severe SMA phenotype. The authors noted that these findings were consistent with observations in humans showing that PLS3 provides full protection against SMA only in SMN1-deleted individuals with 3 to 4 SMN2 copies, but not in those with 2 SMN2 copies. In mildly affected SMA mice, PLS3 delayed axon pruning until postnatal day 8, which counteracted the poor synaptic activity observed in control SMA mice. F-actin content was increased in presynapses, leading to improved neuromuscular connectivity, restored active zone content of synaptic vesicles, improved organization of the ready releasable vesicle pool, increased endplate and muscle fiber size, and improved neurotransmission. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23263861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="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="#Brandt1950" class="mim-tip-reference" title="Brandt, S. <strong>Werdnig-Hoffmann's Infantile Progressive Muscular Atrophy: Clinical Aspects, Pathology, Heredity and Relation to Oppenheim's Amyotonia Congenita and other Morbid Conditions with Laxity of Joints or Muscles in Infants.</strong> Copenhagen: Munksgaard (pub.) 1950.">Brandt (1950)</a>; <a href="#Chow1978" class="mim-tip-reference" title="Chow, S. M., Nanaka, I. <strong>Werdnig-Hoffmann disease: proposal of a pathogenetic mechanism.</strong> Acta Neuropath. 41: 45-54, 1978.">Chow and Nanaka (1978)</a>; <a href="#Cobben1995" class="mim-tip-reference" title="Cobben, J. M., van der Steege, G., Grootscholten, P., de Visser, M., Scheffer, H., Buys, C. H. C. M. <strong>Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy.</strong> Am. J. Hum. Genet. 57: 805-808, 1995.">Cobben et al. (1995)</a>; <a href="#Cunningham1978" class="mim-tip-reference" title="Cunningham, M., Stocks, J. <strong>Werdnig-Hoffmann disease: the effects of intrauterine onset on lung growth.</strong> Arch. Dis. Child. 53: 921-925, 1978.">Cunningham and Stocks (1978)</a>; <a href="#Daniels1992" class="mim-tip-reference" title="Daniels, R. J., Thomas, N. H., MacKinnon, R. N., Lehner, T., Ott, J., Flint, T. J., Dubowitz, V., Ignatius, J., Donner, M., Zerres, K., Rietschel, M., Cookson, W. O. C., Brzustowicz, L. M., Gilliam, T. C., Davies, K. E. <strong>Linkage analysis of spinal muscular atrophy.</strong> Genomics 12: 335-339, 1992.">Daniels et al. (1992)</a>; <a href="#Fried1977" class="mim-tip-reference" title="Fried, K., Mundel, G. <strong>High incidence of spinal muscular atrophy type I (Werdnig-Hoffmann disease) in the Karaite community in Israel.</strong> Clin. Genet. 12: 250-251, 1977.">Fried and Mundel
|
|
(1977)</a>; <a href="#Gamstorp1967" class="mim-tip-reference" title="Gamstorp, I. <strong>Progressive spinal muscular atrophy with onset in infancy or early childhood.</strong> Acta Paediat. Scand. 56: 408-423, 1967.">Gamstorp (1967)</a>; <a href="#Hanhart1945" class="mim-tip-reference" title="Hanhart, E. <strong>Die infantile progressive spinale Muskelatrophie (Werdnig-Hoffmann) als einfach-rezessive, subletale Mutation auf Grund von 29 Faellen in 14 Sippen.</strong> Helv. Paediat. Acta 1: 110-133, 1945.">Hanhart (1945)</a>; <a href="#Hausmanowa-Petrusewicz1985" 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.">Hausmanowa-Petrusewicz et
|
|
al. (1985)</a>; <a href="#Pascalet-Guidon1984" class="mim-tip-reference" title="Pascalet-Guidon, M.-J., Bois, E., Feingold, J., Mattei, J.-F., Combes, J.-C., Hamon, C. <strong>Cluster of acute infantile spinal muscular atrophy (Werdnig-Hoffmann disease) in a limited area of Reunion Island.</strong> Clin. Genet. 26: 39-42, 1984.">Pascalet-Guidon et al. (1984)</a>; <a href="#Wirth1997" class="mim-tip-reference" title="Wirth, B., Schmidt, T., Hahnen, E., Rudnik-Schoneborn, S., Krawczak, M., Muller-Myhsok, B., Schonling, J., Zerres, K. <strong>De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling.</strong> Am. J. Hum. Genet. 61: 1102-1111, 1997.">Wirth et al. (1997)</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="Ackermann2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ackermann, B., Krober, S., Torres-Benito, L., Borgmann, A., Peters, M., Barkooie, S. M. H., Tejero, R., Jakubik, M., Schreml, J., Milbradt, J., Wunderlich, T. F., Riessland, M., Tabares, L., Wirth, B.
|
|
<strong>Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality.</strong>
|
|
Hum. Molec. Genet. 22: 1328-1347, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23263861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23263861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23263861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/dds540" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Alias2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alias, L., Bernal, S., Fuentes-Prior, P., Barcelo, M. J., Also, E., Martinez-Hernandez, R., Rodriguez-Alvarez, F. J., Martin, Y., Aller, E., Grau, E., Pecina, A., Antinolo, G., Galan, E., Rosa, A. L., Fernandez-Burriel, M., Borrego, S., Millan, J. M., Hernandez-Chico, C., Baiget, M., Tizzano, E. F.
|
|
<strong>Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene.</strong>
|
|
Hum. Genet. 125: 29-39, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19050931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19050931</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19050931" 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/s00439-008-0598-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Andreassi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andreassi, C., Angelozzi, C., Tiziano, F. D., Vitali, T., De Vincenzi, E., Boninsegna, A., Villanova, M., Bertini, E., Pini, A., Neri, G., Brahe, C.
|
|
<strong>Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy.</strong>
|
|
Europ. J. Hum. Genet. 12: 59-65, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14560316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14560316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14560316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5201102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Angelozzi2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Angelozzi, C., Borgo, F., Tiziano, F. D., Martella, A., Neri, G., Brahe, C.
|
|
<strong>Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells.</strong>
|
|
J. Med. Genet. 45: 29-31, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2007.051177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Becker1964" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Becker, P. E.
|
|
<strong>Atrophia musculorum spinalis pseudomyopathica. Hereditaere neurogene proximale Amyotrophie von Kugelberg und Welander.</strong>
|
|
Z. Menschl. Vererb. Konstitutionsl. 37: 193-220, 1964.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Biros1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Biros, I., Forrest, S.
|
|
<strong>Spinal muscular dystrophy: untangling the knot?</strong>
|
|
J. Med. Genet. 36: 1-8, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9950358" 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="7" class="mim-anchor"></a>
|
|
<a id="Blazej1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blazej, R. G., Mellersh, C. S., Cork, L. C., Ostrander, E. A.
|
|
<strong>Hereditary canine spinal muscular atrophy is phenotypically similar but molecularly distinct from human spinal muscular atrophy.</strong>
|
|
J. Hered. 89: 531-537, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9864863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9864863</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9864863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/jhered/89.6.531" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Bouwsma1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bouwsma, G., Leschot, N. J.
|
|
<strong>Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis.</strong>
|
|
Clin. Genet. 30: 145-149, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3780029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3780029</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3780029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1986.tb00586.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Bowerman2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bowerman, M., Beauvais, A., Anderson, C. L., Kothary, R.
|
|
<strong>Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model.</strong>
|
|
Hum. Molec. Genet. 19: 1468-1478, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20097679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddq021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Brandt1949" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brandt, S.
|
|
<strong>Hereditary factors in infantile progressive muscular atrophy: study of one hundred and twelve cases in seventy families.</strong>
|
|
Am. J. Dis. Child. 78: 226-236, 1949.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Brandt1950" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brandt, S.
|
|
<strong>Werdnig-Hoffmann's Infantile Progressive Muscular Atrophy: Clinical Aspects, Pathology, Heredity and Relation to Oppenheim's Amyotonia Congenita and other Morbid Conditions with Laxity of Joints or Muscles in Infants.</strong>
|
|
Copenhagen: Munksgaard (pub.) 1950.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Brichta2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F. A., Raschke, H., Blumcke, I., Eyupoglu, I. Y., Wirth, B.
|
|
<strong>Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 12: 2481-2489, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg256" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Brichta2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brichta, L., Holker, I., Haug, K., Klockgether, T., Wirth, B.
|
|
<strong>In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate.</strong>
|
|
Ann. Neurol. 59: 970-975, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16607616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20836" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Brzustowicz1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brzustowicz, L. M., Kleyn, P. W., Boyce, F. M., Lien, L. L., Monaco, A. P., Penchaszadeh, G. K., Das, K., Wang, C. H., Munsat, T. L., Ott, J., Kunkel, L. M., Gilliam, T. C.
|
|
<strong>Fine-mapping of the spinal muscular atrophy locus to a region flanked by MAP1B and D5S6.</strong>
|
|
Genomics 13: 991-998, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505990</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1505990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90012-h" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Burd1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burd, L., Short, S. K., Martsolf, J. T., Nelson, R. A.
|
|
<strong>Prevalence of type I spinal muscular atrophy in North Dakota.</strong>
|
|
Am. J. Med. Genet. 41: 212-215, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1785637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1785637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1785637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320410216" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Burghes1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burghes, A. H. M.
|
|
<strong>When is a deletion not a deletion? When it is converted. (Editorial)</strong>
|
|
Am. J. Hum. Genet. 61: 9-15, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9245977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/513913" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Burlet1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burlet, P., Burglen, L., Clermont, O., Lefebvre, S., Viollet, L., Munnich, A., Melki, J.
|
|
<strong>Large scale deletions of the 5q13 region are specific to Werdnig-Hoffmann disease.</strong>
|
|
J. Med. Genet. 33: 281-283, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8730281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8730281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8730281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.33.4.281" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Butchbach2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Butchbach, M. E. R., Singh, J., Porsteinsdottir, M., Saieva, L., Slominski, E., Thurmond, J., Andresson, T., Zhang, J., Edwards, J. D., Simard, L. R., Pellizzoni, L., Jarecki, J., Burghes, A. H. M., Gurney, M. E.
|
|
<strong>Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 454-467, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19897588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19897588</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19897588[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=19897588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp510" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Campbell1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K.
|
|
<strong>Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.</strong>
|
|
Am. J. Hum. Genet. 61: 40-50, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245983</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9245983" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/513886" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Chan2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, Y. B., Miguel-Aliaga, I., Franks, C., Thomas, N., Trulzsch, B., Sattelle, D. B., Davies, K. E., van den Heuvel, M.
|
|
<strong>Neuromuscular defects in a Drosophila survival motor neuron gene mutant.</strong>
|
|
Hum. Molec. Genet. 12: 1367-1376, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12783845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12783845</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12783845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg157" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Chang2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chang, J.-G., Hsieh-Li, H.-M., Jong, Y.-J., Wang, N. M., Tsai, C.-H., Li, H.
|
|
<strong>Treatment of spinal muscular atrophy by sodium butyrate.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 9808-9813, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11504946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11504946</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11504946[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=11504946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.171105098" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Chong2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chong, J. X., Oktay, A. A., Dai, Z., Swoboda, K .J., Prior, T. W., Ober, C.
|
|
<strong>A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites.</strong>
|
|
Europ. J. Hum. Genet. 19: 1045-1051, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21610747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21610747</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21610747[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=21610747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2011.85" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Chow1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chow, S. M., Nanaka, I.
|
|
<strong>Werdnig-Hoffmann disease: proposal of a pathogenetic mechanism.</strong>
|
|
Acta Neuropath. 41: 45-54, 1978.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Cobben1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cobben, J. M., van der Steege, G., Grootscholten, P., de Visser, M., Scheffer, H., Buys, C. H. C. M.
|
|
<strong>Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy.</strong>
|
|
Am. J. Hum. Genet. 57: 805-808, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573039/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573039</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573039" 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="25" class="mim-anchor"></a>
|
|
<a id="Cunningham1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cunningham, M., Stocks, J.
|
|
<strong>Werdnig-Hoffmann disease: the effects of intrauterine onset on lung growth.</strong>
|
|
Arch. Dis. Child. 53: 921-925, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/747396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">747396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=747396" 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/adc.53.12.921" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Czeizel1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Czeizel, A., Hamula, J.
|
|
<strong>A Hungarian study on Werdnig-Hoffmann disease.</strong>
|
|
J. Med. Genet. 26: 761-763, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2614795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2614795</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2614795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.26.12.761" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Czeizel1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Czeizel, A.
|
|
<strong>High incidence of acute infantile spinal atrophy in Hungary. (Letter)</strong>
|
|
Hum. Genet. 86: 539, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2016096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2016096</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2016096" 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/BF00194653" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Daniels1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Daniels, R. J., Suthers, G. K., Morrison, K. E., Thomas, N. H., Francis, M. J., Mathew, C. G., Loughlin, S., Heiberg, A., Wood, D., Dubowitz, V., Davies, K. E.
|
|
<strong>Prenatal prediction of spinal muscular atrophy.</strong>
|
|
J. Med. Genet. 29: 165-170, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348091</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.29.3.165" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Daniels1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Daniels, R. J., Thomas, N. H., MacKinnon, R. N., Lehner, T., Ott, J., Flint, T. J., Dubowitz, V., Ignatius, J., Donner, M., Zerres, K., Rietschel, M., Cookson, W. O. C., Brzustowicz, L. M., Gilliam, T. C., Davies, K. E.
|
|
<strong>Linkage analysis of spinal muscular atrophy.</strong>
|
|
Genomics 12: 335-339, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346777</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90382-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="des Portes1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
des Portes, V., Coulpier, M., Melki, J., Dreyfus, P. A.
|
|
<strong>Early detection of mouse wobbler mutation: a model of pathological motoneurone death.</strong>
|
|
Neuroreport 5: 1861-1864, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7841363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7841363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7841363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00001756-199410000-00005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Ebert2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N.
|
|
<strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong>
|
|
Nature 457: 277-280, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098894[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=19098894" 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/nature07677" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Feingold1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Feingold, J., Arthuis, M., Celers, J.
|
|
<strong>Genetique de l'amyotrophie spinale infantile: existence de deux formes autosomiques recessives.</strong>
|
|
Ann. Genet. 20: 19-23, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/302668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">302668</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=302668" 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="33" class="mim-anchor"></a>
|
|
<a id="Fried1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fried, K., Mundel, G.
|
|
<strong>High incidence of spinal muscular atrophy type I (Werdnig-Hoffmann disease) in the Karaite community in Israel.</strong>
|
|
Clin. Genet. 12: 250-251, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/912942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">912942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=912942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1977.tb00934.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Frugier2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frugier, T., Tiziano, F. D., Cifuentes-Diaz, C., Miniou, P., Roblot, N., Dierich, A., Le Meur, M., Melki, J.
|
|
<strong>Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 9: 849-858, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.5.849" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Gamstorp1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gamstorp, I.
|
|
<strong>Progressive spinal muscular atrophy with onset in infancy or early childhood.</strong>
|
|
Acta Paediat. Scand. 56: 408-423, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6039049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6039049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6039049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1651-2227.1967.tb15400.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Gavrilina2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U. R., Morris, G. E., Burghes, A. H. M.
|
|
<strong>Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect.</strong>
|
|
Hum. Molec. Genet. 17: 1063-1075, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178576</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18178576[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=18178576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddm379" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Ghetti1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ghetti, B., Amati, A., Turra, M. V., Pacini, A., Del Vecchio, M., Guazzi, G. C.
|
|
<strong>Werdnig-Hoffmann-Wohlfart-Kugelberg-Welander disease: nosological unity and clinical variability in intrafamilial cases.</strong>
|
|
Acta Genet. Med. Gemellol. 20: 43-58, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5568110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5568110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5568110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1017/s1120962300011707" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Gilliam1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gilliam, T. C., Brzustowicz, L. M., Castilla, L. H., Lehner, T., Penchaszadeh, G. K., Daniels, R. J., Byth, B. C., Knowles, J., Hislop, J. E., Shapira, Y., Dubowitz, V., Munsat, T. L., Ott, J., Davies, K. E.
|
|
<strong>Genetic homogeneity between acute and chronic forms of spinal muscular atrophy.</strong>
|
|
Nature 345: 823-825, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1972783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1972783</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1972783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/345823a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Gilliam1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gilliam, T. C.
|
|
<strong>Is the spinal muscular atrophy gene found?</strong>
|
|
Nature Med. 1: 124-127, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585007" 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/nm0295-124" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Grzeschik2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grzeschik, S. M., Ganta, M., Prior, T. W., Heavlin, W. D., Wang, C. H.
|
|
<strong>Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells.</strong>
|
|
Ann. Neurol. 58: 194-202, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16049920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16049920</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16049920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20548" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Hahnen1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hahnen, E., Schonling, J., Rudnik-Schoneborn, S., Zerres, K., Wirth, B.
|
|
<strong>Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease.</strong>
|
|
Am. J. Hum. Genet. 59: 1057-1065, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900234" 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="42" class="mim-anchor"></a>
|
|
<a id="Hanhart1945" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hanhart, E.
|
|
<strong>Die infantile progressive spinale Muskelatrophie (Werdnig-Hoffmann) als einfach-rezessive, subletale Mutation auf Grund von 29 Faellen in 14 Sippen.</strong>
|
|
Helv. Paediat. Acta 1: 110-133, 1945.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" 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="44" class="mim-anchor"></a>
|
|
<a id="Hendrickson2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hendrickson, B. C., Donohoe, C., Akmaev, V. R., Sugarman, E. A., Labrousse, P., Boguslavskiy, L., Flynn, K., Rohlfs, E. M., Walker, A., Allitto, B., Sears, C., Scholl, T.
|
|
<strong>Differences in SMN1 allele frequencies among ethnic groups within North America. (Letter)</strong>
|
|
J. Med. Genet. 46: 641-644, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19625283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19625283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19625283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2009.066969" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Heng1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heng, H. H. Q., Xie, B., Shi, X.-M., Tsui, L.-C., Mahuran, D. J.
|
|
<strong>Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus.</strong>
|
|
Genomics 18: 429-431, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8288250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8288250</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8288250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1993.1491" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Hogenhuis1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hogenhuis, L. A. H., Spaulding, S. W., Engel, W. K.
|
|
<strong>Neuronal RNA metabolism in infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) studied by radioautography: a new technic in the investigation of neurological disease.</strong>
|
|
J. Neuropath. Exp. Neurol. 26: 335-341, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6022173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6022173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6022173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00005072-196704000-00010" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Hsieh-Li2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hsieh-Li, H. M., Chang, J.-G., Jong, Y.-J., Wu, M.-H., Wang, N. M., Tsai, C. H., Li, H.
|
|
<strong>A mouse model for spinal muscular atrophy.</strong>
|
|
Nature Genet. 24: 66-70, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615130</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10615130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/71709" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Jedrzejowska2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jedrzejowska, M., Borkowska, J., Zimowski, J., Kostera-Pruszczyk, A., Milewski, M., Jurek, M., Sielska, D., Kostyk, E., Nyka, W., Zaremba, J., Hausmanowa-Petrusewicz, I.
|
|
<strong>Unaffected patients with a homozygous absence of the SMN1 gene.</strong>
|
|
Europ. J. Hum. Genet. 16: 930-934, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337729</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337729" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2008.41" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Kariya2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kariya, S., Park, G.-H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M. S., Landmesser, L. T., Monani, U. R.
|
|
<strong>Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 17: 2552-2569, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492800</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492800[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=18492800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddn156" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Kaupmann1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kaupmann, K., Simon-Chazottes, D., Guenet, J.-L., Jockusch, H.
|
|
<strong>Wobbler, a mutation affecting motoneuron survival and gonadal functions in the mouse, maps to proximal chromosome 11.</strong>
|
|
Genomics 13: 39-43, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1349581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90199-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Kleyn1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kleyn, P. W., Brzustowicz, L. M., Wilhelmsen, K. C., Freimer, N. B., Miller, J. M., Munsat, T. L., Gilliam, T. C.
|
|
<strong>Spinal muscular atrophy is not the result of mutations at the beta-hexosaminidase or GM(2)-activator locus.</strong>
|
|
Neurology 41: 1418-1422, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1679910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1679910</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1679910" 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.41.9.1418" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Kye2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kye, M. J., Niederst, E. D., Wertz, M. H., Goncalves, I. C. G., Akten, B., Dover, K. Z., Peters, M., Riessland, M., Neveu, P., Wirth, B., Kosik, K. S., Sardi, S. P., Monani, U. R., Passini, M. A., Sahin, M.
|
|
<strong>SMN regulates axonal local translation via miR-183/mTOR pathway.</strong>
|
|
Hum. Molec. Genet. 23: 6318-6331, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25055867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25055867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25055867[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=25055867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddu350" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Lazarin2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S.
|
|
<strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong>
|
|
Genet. Med. 15: 178-186, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22975760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22975760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22975760" 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/gim.2012.114" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Lefebvre1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lefebvre, S., Burglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., Le Paslier, D., Frezal, J., Cohen, D., Weissenbach, J., Munnich, A., Melki, J.
|
|
<strong>Identification and characterization of a spinal muscular atrophy-determining gene.</strong>
|
|
Cell 80: 155-165, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813012</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7813012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(95)90460-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Lewin1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lewin, B.
|
|
<strong>Genes for SMA: multum in parvo.</strong>
|
|
Cell 80: 1-5, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813005</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7813005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(95)90442-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Lien1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lien, L. L., Boyce, F. M., Kleyn, P., Brzustowicz, L. M., Menninger, J., Ward, D. C., Gilliam, T. C., Kunkel, L. M.
|
|
<strong>Mapping of a gene encoding a dystrophin cross-reactive protein in close proximity to the spinal muscular atrophy locus. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49 (suppl.): 412, 1991.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Lorson1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lorson, C. L., Hahnen, E., Androphy, E. J., Wirth, B.
|
|
<strong>A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 6307-6311, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10339583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10339583</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10339583[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=10339583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.11.6307" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Lumaka2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lumaka, A., Bone, D., Lukoo, R., Mujinga, N., Senga, I., Tady, B., Matthijs, G., Lukusa, T. P.
|
|
<strong>Werdnig-Hoffmann disease: report of the first case clinically identified and genetically confirmed in Central Africa (Kinshasa-Congo).</strong>
|
|
Genet. Counsel. 20: 349-358, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20162870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20162870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20162870" 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="59" class="mim-anchor"></a>
|
|
<a id="Lunn2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lunn, M. R., Wang, C. H.
|
|
<strong>Spinal muscular atrophy.</strong>
|
|
Lancet 371: 2120-2133, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18572081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18572081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18572081" 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/S0140-6736(08)60921-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Marquardt1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marquardt, J. E., MacLowry, J., Perry, R. E.
|
|
<strong>Infantile progressive spinal muscular atrophy in identical Negro twins.</strong>
|
|
New Eng. J. Med. 267: 386-388, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14470139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14470139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14470139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM196208232670804" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Mattei1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mattei, M.-G., Melki, J., Bachelot, M.-F., Abdelhak, S., Burlet, P., Frezal, J., Munnich, A.
|
|
<strong>In situ hybridization of two markers closely flanking the spinal muscular atrophy gene to 5q12-q13.3.</strong>
|
|
Cytogenet. Cell Genet. 57: 112-113, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1914518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1914518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1914518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000133125" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Matthijs1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthijs, G., Schollen, E., Legius, E., Devriendt, K., Goemans, N., Kayserili, H., Apak, M. Y., Cassiman, J.-J.
|
|
<strong>Unusual molecular findings in autosomal recessive spinal muscular atrophy.</strong>
|
|
J. Med. Genet. 33: 469-474, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8782046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.33.6.469" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Mattis2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mattis, V. B., Ebert, A. D., Fosso, M. Y., Chang, C.-W., Lorson, C. L.
|
|
<strong>Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model.</strong>
|
|
Hum. Molec. Genet. 18: 3906-3913, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19625298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19625298</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19625298[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=19625298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp333" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Medugorac2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Medugorac, I., Kemter, J., Russ, I., Pietrowski, D., Nuske, S., Reichenbach, H.-D., Schmahl, W., Forster, M.
|
|
<strong>Mapping of the bovine spinal muscular atrophy locus to chromosome 24.</strong>
|
|
Mammalian Genome 14: 383-391, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12879360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12879360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12879360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00335-002-3024-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Melki1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Melki, J., Abdelhak, S., Burlet, P., Raclin, V., Kaplan, J., Spiegel, R., Gilgenkrantz, S., Philip, N., Chauvet, M.-L., Dumez, Y., Briard, M.-L., Frezal, J., Munnich, A.
|
|
<strong>Prenatal prediction of Werdnig-Hoffmann disease using linked polymorphic DNA probes.</strong>
|
|
J. Med. Genet. 29: 171-174, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.29.3.171" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Melki1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Melki, J., Lefebvre, S., Burglen, L., Burlet, P., Clermont, O., Millasseau, P., Reboullet, S., Benichou, B., Zeviani, M., Le Paslier, D., Cohen, D., Weissenbach, J., Munnich, A.
|
|
<strong>De novo and inherited deletions of the 5q13 region in spinal muscular atrophies.</strong>
|
|
Science 264: 1474-1477, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7910982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7910982</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7910982" 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.7910982" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Melki1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Melki, J., Sheth, P., Abdelhak, S., Burlet, P., Bachelot, M.-F., Lathrop, M. G., Frezal, J., Munnich, A., the French Spinal Muscular Atrophy Investigators.
|
|
<strong>Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14.</strong>
|
|
Lancet 336: 271-273, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973971</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1973971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0140-6736(90)91803-i" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Meyer2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer, K., Marquis, J., Trub, J., Nlend Nlend, R., Verp, S., Ruepp, M.-D., Imboden, H., Barde, I., Trono, D., Schumperli, D.
|
|
<strong>Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation.</strong>
|
|
Hum. Molec. Genet. 18: 546-555, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19010792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19010792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19010792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddn382" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Mostacciuolo1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mostacciuolo, M. L., Danieli, G. A., Trevisan, C., Muller, E., Angelini, C.
|
|
<strong>Epidemiology of spinal muscular atrophies in a sample of the Italian population.</strong>
|
|
Neuroepidemiology 11: 34-38, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1608493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1608493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1608493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000110905" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Muller1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muller, B., Melki, J., Burlet, P., Clerget-Darpoux, F.
|
|
<strong>Proximal spinal muscular atrophy (SMA) types II and III in the same sibship are not caused by different alleles at the SMA locus on 5q.</strong>
|
|
Am. J. Hum. Genet. 50: 892-895, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1570842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1570842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1570842" 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="71" class="mim-anchor"></a>
|
|
<a id="Murray2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murray, L. M., Lee, S., Baumer, D., Parson, S. H., Talbot, K., Gillingwater, T. H.
|
|
<strong>Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 420-433, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19884170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19884170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19884170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp506" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Narver2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Narver, H. L., Kong, L., Burnett, B. G., Choe, D. W., Bosch-Marce, M., Taye, A. A., Eckhaus, M. A., Sumner, C. J.
|
|
<strong>Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition.</strong>
|
|
Ann. Neurol. 64: 465-470, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18661558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18661558</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18661558[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=18661558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.21449" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Naryshkin2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Naryshkin, N. A., Weetall, M., Dakka, A., Narasimhan, J., Zhao, X., Feng, Z., Ling, K. K. Y., Karp, G. M., Qi, H., Woll, M. G., Chen, G., Zhang, N., and 36 others.
|
|
<strong>SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy.</strong>
|
|
Science 345: 688-693, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25104390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25104390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25104390" 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.1250127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Novelli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Novelli, G., Semprini, S., Capon, F., Dallapiccola, B.
|
|
<strong>A possible role of NAIP gene deletions in sex-related spinal muscular atrophy phenotype variation.</strong>
|
|
Neurogenetics 1: 29-30, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10735271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10735271</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10735271" 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/s100480050004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Ogino2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ogino, S., Wilson, R. B.
|
|
<strong>Spinal muscular atrophy: molecular genetics and diagnosis.</strong>
|
|
Expert Rev. Molec. Diagn. 4: 15-29, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14711346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14711346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14711346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1586/14737159.4.1.15" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Oprea2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oprea, G. E., Kroeber, S., McWhorter, M. L., Rossoll, W., Mueller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., Wirth, B.
|
|
<strong>Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy.</strong>
|
|
Science 320: 524-527, 2008. Note: Erratum: Science 384: eadq4773, 2024.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Oskoui2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oskoui, M., Levy, G., Garland, C. J., Gray, J. M., O'Hagen, J., De Vivo, D. C., Kaufmann, P.
|
|
<strong>The changing natural history of spinal muscular atrophy type 1.</strong>
|
|
Neurology 69: 1931-1936, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17998484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000290830.40544.b9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Pascalet-Guidon1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pascalet-Guidon, M.-J., Bois, E., Feingold, J., Mattei, J.-F., Combes, J.-C., Hamon, C.
|
|
<strong>Cluster of acute infantile spinal muscular atrophy (Werdnig-Hoffmann disease) in a limited area of Reunion Island.</strong>
|
|
Clin. Genet. 26: 39-42, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6467653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6467653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6467653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1984.tb00785.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Pearn1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pearn, J. K., Carter, C. O., Wilson, J.
|
|
<strong>The genetic identity of acute infantile spinal muscular atrophy.</strong>
|
|
Brain 96: 463-470, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4743929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4743929</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4743929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/brain/96.3.463" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Roy1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roy, N., Mahadevan, M. S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X., Salih, M., Aubry, H., Tamai, K., Guan, X., Ioannou, P., Crawford, T. O., de Jong, P. J., Surh, L., Ikeda, J.-E., Korneluk, R. G., MacKenzie, A.
|
|
<strong>The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.</strong>
|
|
Cell 80: 167-178, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813013</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7813013" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(95)90461-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Rudnik-Schoneborn2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Berg, C., Zerres, K., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Heller, R.
|
|
<strong>Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling.</strong>
|
|
Clin. Genet. 76: 168-178, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19780763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19780763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19780763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2009.01200.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Rudnik-Schoneborn2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Heller, R., Berg, C., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Zerres, K.
|
|
<strong>Congenital heart disease is a feature of severe infantile spinal muscular atrophy.</strong>
|
|
J. Med. Genet. 45: 635-638, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18662980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18662980</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18662980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2008.057950" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Samilchuk1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Samilchuk, E., D'Souza, B., Bastaki, L.
|
|
<strong>Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy.</strong>
|
|
Hum. Genet. 98: 524-527, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882869</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8882869" 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/s004390050253" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Scharf1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scharf, J. M., Endrizzi, M. G., Wetter, A., Huang, S., Thompson, T. G., Zerres, K., Dietrich, W. F., Wirth, B., Kunkel, L. M.
|
|
<strong>Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics.</strong>
|
|
Nature Genet. 20: 83-86, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/1753" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Sheng-Yuan2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sheng-Yuan, Z., Xiong, F., Chen, Y.-J., Yan, T.-Z., Zeng, J., Li, L., Zhang, Y.-N., Chen, W.-Q., Bao, X.-H., Zhang, C., Xu, X.-M.
|
|
<strong>Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.</strong>
|
|
Europ. J. Hum. Genet. 18: 978-984, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20442745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20442745</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20442745[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=20442745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2010.54" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Somerville1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Somerville, M. J., Hunter, A. G. W., Aubry, H. L., Korneluk, R. G., MacKenzie, A. E., Surh, L. C.
|
|
<strong>Clinical application of the molecular diagnosis of spinal muscular atrophy: deletions of neuronal apoptosis inhibitor protein and survival motor neuron genes.</strong>
|
|
Am. J. Med. Genet. 69: 159-165, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9056553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9056553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9056553" 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="87" class="mim-anchor"></a>
|
|
<a id="Soubrouillard1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Soubrouillard, C., Pellissier, J. F., Lepidi, H., Mancini, J., Rougon, G., Figarella-Branger, D.
|
|
<strong>Expression of developmentally regulated cytoskeleton and cell surface proteins in childhood spinal muscular atrophies.</strong>
|
|
J. Neurol. Sci. 133: 155-163, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8583219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8583219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8583219" 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(95)00182-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Spiegler1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spiegler, A. W. J., Hausmanowa-Petrusewicz, I., Borkowska, J., Klopocka, A.
|
|
<strong>Population data on acute infantile and chronic childhood spinal muscular atrophy in Warsaw.</strong>
|
|
Hum. Genet. 85: 211-214, 1990.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Stratigopoulos2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stratigopoulos, G., Lanzano, P., Deng, L., Guo, J., Kaufmann, P., Darras, B., Finkel, R., Tawil, R., McDermott, M. P., Martens, W., Devivo, D. C., Chung, W. K.
|
|
<strong>Association of plastin 3 expression with disease severity in spinal muscular atrophy only in postpubertal females.</strong>
|
|
Arch. Neurol. 67: 1252-1256, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20937953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20937953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20937953" 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/archneurol.2010.239" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Thomas1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomas, N. H., Dubowitz, V.
|
|
<strong>The natural history of type I (severe) spinal muscular atrophy.</strong>
|
|
Neuromusc. Disord. 4: 497-502, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7881295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7881295</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7881295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0960-8966(94)90090-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Thompson1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, T. G., DiDonato, C. J., Simard, L. R., Ingraham, S. E., Burghes, A. H. M., Crawford, T. O., Rochette, C., Mendell, J. R., Wasmuth, J. J.
|
|
<strong>A novel cDNA detects homozygous microdeletions in greater than 50% of type I spinal muscular atrophy patients..</strong>
|
|
Nature Genet. 9: 56-62, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7704025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7704025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7704025" 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/ng0195-56" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Ting2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ting, C.-H., Lin, C.-W., Wen, S.-L., Hsieh-Li, H.-M., Li, H.
|
|
<strong>Stat5 constitutive activation rescues defects in spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 16: 499-514, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17220171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17220171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17220171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddl482" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Wen2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wen, H.-L., Lin, Y.-T., Ting, C.-H., Lin-Chao, S., Li, H., Hsieh-Li, H. M.
|
|
<strong>Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 1766-1778, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20176735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20176735</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20176735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddq058" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Wilmshurst2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilmshurst, J. M., Reynolds, L., Van Toorn, R., Leisegang, F., Henderson, H. E.
|
|
<strong>Spinal muscular atrophy in black South Africans: concordance with the universal SMN1 genotype.</strong>
|
|
Clin. Genet. 62: 165-168, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2002.620210.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Wilson2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilson, R. B., Ogino, S.
|
|
<strong>Carrier frequency of spinal muscular atrophy. (Letter)</strong>
|
|
Lancet 372: 1542 only, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18984183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18984183</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18984183" 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/S0140-6736(08)61645-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Wirth1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wirth, B., Rudnik-Schoneborn, S., Hahnen, E., Rohrig, D., Zerres, K.
|
|
<strong>Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2-q13.3): molecular genetics and clinical experience in 109 cases.</strong>
|
|
Prenatal Diag. 15: 407-417, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7644431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7644431</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7644431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/pd.1970150503" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Wirth1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wirth, B., Schmidt, T., Hahnen, E., Rudnik-Schoneborn, S., Krawczak, M., Muller-Myhsok, B., Schonling, J., Zerres, K.
|
|
<strong>De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling.</strong>
|
|
Am. J. Hum. Genet. 61: 1102-1111, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301608" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Wirth1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wirth, B., Voosen, B., Rohrig, D., Knapp, M., Piechaczek, B., Rudnik-Schoneborn, S., Zerres, K.
|
|
<strong>Fine mapping and narrowing of the genetic interval of the spinal muscular atrophy region by linkage studies.</strong>
|
|
Genomics 15: 113-118, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1993.1018" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Wirth2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wirth, B.
|
|
<strong>An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA).</strong>
|
|
Hum. Mutat. 15: 228-237, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10679938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10679938</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10679938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Wishart2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wishart, T. M., Huang, J. P.-W., Murray, L. M., Lamont, D. J., Mutsaers, C. A., Ross, J., Geldsetzer, P., Ansorge, O., Talbot, K., Parson, S. H., Gillingwater, T. H.
|
|
<strong>SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 4216-4228, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20705736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20705736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20705736[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=20705736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddq340" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Workman2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Workman, E., Saieva, L., Carrel, T. L., Crawford, T. O., Liu, D., Lutz, C., Beattie, C. E., Pellizzoni, L., Burghes, A. H. M.
|
|
<strong>A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice.</strong>
|
|
Hum. Molec. Genet. 18: 2215-2229, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329542</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329542[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=19329542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp157" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Yuo2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yuo, C.-Y., Lin, H.-H., Chang, Y.-S., Yang, W.-K., Chang, J.-G.
|
|
<strong>5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells.</strong>
|
|
Ann. Neurol. 63: 26-34, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17924536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17924536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17924536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.21241" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Zaldivar2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zaldivar, T., Montejo, Y., Acevedo, A. M., Guerra, R., Vargas, J., Garofalo, N., Alvarez, R., Alvarez, M. A., Hardiman, O.
|
|
<strong>Evidence of reduced frequency of spinal muscular atrophy type I in the Cuban population.</strong>
|
|
Neurology 65: 636-638, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116135</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000172860.41953.12" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Zerres1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zerres, K., Grimm, T.
|
|
<strong>Genetic counseling in families with spinal muscular atrophy type Kugelberg-Welander.</strong>
|
|
Hum. Genet. 65: 74-75, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6642509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6642509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6642509" 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/BF00285033" 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">
|
|
George E. Tiller - updated : 06/23/2017
|
|
</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">
|
|
Patricia A. Hartz - updated : 01/20/2015<br>Ada Hamosh - updated : 8/29/2014<br>Patricia A. Hartz - updated : 9/4/2013<br>Anne M. Stumpf - updated : 4/18/2013<br>Cassandra L. Kniffin - updated : 3/21/2012<br>Cassandra L. Kniffin - updated : 1/10/2012<br>George E. Tiller - updated : 12/1/2011<br>George E. Tiller - updated : 11/21/2011<br>Cassandra L. Kniffin - updated : 10/10/2011<br>Cassandra L. Kniffin - updated : 7/21/2011<br>George E. Tiller - updated : 1/5/2011<br>George E. Tiller - updated : 8/10/2010<br>Cassandra L. Kniffin - updated : 6/8/2010<br>Cassandra L. Kniffin - updated : 3/15/2010<br>George E. Tiller - updated : 3/3/2010<br>Cassandra L. Kniffin - updated : 12/30/2009<br>Cassandra L. Kniffin - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 11/2/2009<br>Cassandra L. Kniffin - updated : 8/28/2009<br>George E. Tiller - updated : 8/14/2009<br>Cassandra L. Kniffin - updated : 7/14/2009<br>Cassandra L. Kniffin - updated : 2/25/2009<br>Ada Hamosh - updated : 2/24/2009<br>Cassandra L. Kniffin - updated : 2/12/2009<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Ada Hamosh - updated : 6/17/2008<br>Cassandra L. Kniffin - updated : 5/12/2008<br>Cassandra L. Kniffin - updated : 3/6/2008<br>Cassandra L. Kniffin - updated : 8/6/2007<br>Cassandra L. Kniffin - updated : 12/5/2005<br>Cassandra L. Kniffin - reorganized : 11/21/2005<br>Cassandra L. Kniffin - updated : 11/2/2005<br>George E. Tiller - updated : 9/12/2005<br>George E. Tiller - updated : 3/17/2005<br>George E. Tiller - updated : 3/17/2005<br>Cassandra L. Kniffin - updated : 5/7/2004<br>Victor A. McKusick - updated : 12/9/2003<br>Victor A. McKusick - updated : 11/25/2002<br>Victor A. McKusick - updated : 10/15/2001<br>George E. Tiller - updated : 1/16/2001<br>George E. Tiller - updated : 12/4/2000<br>Victor A. McKusick - updated : 3/15/1999<br>Michael J. Wright - updated : 2/11/1999<br>Victor A. McKusick - updated : 8/28/1998<br>Victor A. McKusick - updated : 11/26/1997<br>Victor A. McKusick - updated : 9/5/1997<br>Victor A. McKusick - updated : 8/20/1997<br>Victor A. McKusick - updated : 5/15/1997<br>Victor A. McKusick - updated : 4/15/1997<br>Moyra Smith - updated : 1/14/1997<br>Moyra Smith - updated : 12/31/1996<br>Iosif W. Lurie - updated : 7/10/1996<br>Moyra Smith - updated : 4/23/1996<br>Orest Hurko - updated : 3/6/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</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 : 07/19/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 01/20/2022<br>carol : 04/02/2021<br>mgross : 02/15/2018<br>alopez : 06/23/2017<br>carol : 05/01/2017<br>carol : 03/25/2017<br>alopez : 09/16/2016<br>mgross : 01/20/2015<br>alopez : 8/29/2014<br>mgross : 9/4/2013<br>alopez : 5/30/2013<br>alopez : 4/18/2013<br>mgross : 5/11/2012<br>carol : 3/21/2012<br>carol : 3/21/2012<br>ckniffin : 1/10/2012<br>alopez : 12/5/2011<br>terry : 12/1/2011<br>carol : 11/22/2011<br>carol : 11/21/2011<br>terry : 11/21/2011<br>carol : 10/12/2011<br>ckniffin : 10/10/2011<br>wwang : 7/26/2011<br>ckniffin : 7/21/2011<br>wwang : 1/14/2011<br>terry : 1/5/2011<br>wwang : 8/10/2010<br>carol : 7/30/2010<br>wwang : 6/15/2010<br>ckniffin : 6/8/2010<br>terry : 5/11/2010<br>wwang : 3/19/2010<br>ckniffin : 3/15/2010<br>wwang : 3/15/2010<br>terry : 3/3/2010<br>wwang : 1/21/2010<br>carol : 1/8/2010<br>ckniffin : 12/30/2009<br>wwang : 12/1/2009<br>wwang : 11/24/2009<br>ckniffin : 11/10/2009<br>carol : 11/4/2009<br>ckniffin : 11/2/2009<br>wwang : 10/30/2009<br>ckniffin : 8/28/2009<br>wwang : 8/14/2009<br>wwang : 7/30/2009<br>ckniffin : 7/14/2009<br>carol : 3/5/2009<br>ckniffin : 2/25/2009<br>alopez : 2/24/2009<br>wwang : 2/20/2009<br>ckniffin : 2/12/2009<br>wwang : 8/28/2008<br>terry : 8/26/2008<br>ckniffin : 8/19/2008<br>alopez : 6/20/2008<br>alopez : 6/20/2008<br>terry : 6/17/2008<br>wwang : 5/19/2008<br>ckniffin : 5/12/2008<br>wwang : 5/8/2008<br>ckniffin : 3/6/2008<br>wwang : 8/21/2007<br>ckniffin : 8/6/2007<br>carol : 2/1/2006<br>wwang : 12/5/2005<br>carol : 11/22/2005<br>carol : 11/21/2005<br>ckniffin : 11/2/2005<br>alopez : 10/20/2005<br>terry : 9/12/2005<br>alopez : 3/17/2005<br>alopez : 3/17/2005<br>tkritzer : 5/10/2004<br>ckniffin : 5/7/2004<br>tkritzer : 12/17/2003<br>terry : 12/9/2003<br>carol : 11/14/2003<br>cwells : 11/25/2002<br>terry : 11/20/2002<br>ckniffin : 5/7/2002<br>cwells : 3/13/2002<br>mcapotos : 10/15/2001<br>mcapotos : 1/26/2001<br>mcapotos : 1/19/2001<br>mcapotos : 1/16/2001<br>terry : 12/4/2000<br>carol : 8/26/1999<br>terry : 7/7/1999<br>carol : 3/15/1999<br>terry : 3/15/1999<br>carol : 2/17/1999<br>terry : 2/11/1999<br>dkim : 12/10/1998<br>carol : 11/16/1998<br>alopez : 8/31/1998<br>terry : 8/28/1998<br>terry : 12/3/1997<br>terry : 11/26/1997<br>terry : 9/12/1997<br>terry : 9/5/1997<br>jenny : 8/22/1997<br>terry : 8/20/1997<br>jenny : 5/15/1997<br>terry : 5/12/1997<br>jenny : 4/15/1997<br>terry : 4/8/1997<br>terry : 1/14/1997<br>mark : 1/14/1997<br>mark : 12/31/1996<br>joanna : 12/2/1996<br>carol : 7/10/1996<br>carol : 4/26/1996<br>carol : 4/23/1996<br>terry : 4/15/1996<br>mark : 3/6/1996<br>terry : 2/29/1996<br>mimman : 2/8/1996<br>mark : 9/12/1995<br>terry : 2/27/1995<br>carol : 2/17/1995<br>jason : 6/15/1994<br>mimadm : 5/4/1994<br>warfield : 3/30/1994
|
|
</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> 253300
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SPINAL MUSCULAR ATROPHY, TYPE I; SMA1
|
|
|
|
</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">
|
|
SMA I<br />
|
|
SMA, INFANTILE ACUTE FORM<br />
|
|
MUSCULAR ATROPHY, INFANTILE<br />
|
|
WERDNIG-HOFFMANN DISEASE
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 64383006;
|
|
|
|
|
|
<strong>ICD10CM:</strong> G12.0;
|
|
|
|
|
|
<strong>ICD9CM:</strong> 335.0;
|
|
|
|
|
|
<strong>ORPHA:</strong> 70, 83330;
|
|
|
|
|
|
<strong>DO:</strong> 13137;
|
|
|
|
|
|
</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">
|
|
5q13.2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Spinal muscular atrophy-1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
253300
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
SMN1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600354
|
|
</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 spinal muscular atrophy type I (SMA1) is caused by mutation or deletion in the telomeric copy of the SMN gene, known as SMN1 (600354), on chromosome 5q13.</p><p>Changes in expression of the centromeric copy of SMN, SMN2 (601627), are known to modify the phenotype.</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 refers to a group of autosomal recessive neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy (summary by Wirth, 2000). </p><p>Four types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: type I, severe infantile acute SMA, or Werdnig-Hoffman disease; type II (253550), or infantile chronic SMA; type III (253400), juvenile SMA, or Wohlfart-Kugelberg-Welander disease; and type IV (271150), or adult-onset SMA. All types are caused by recessive mutations in the SMN1 gene.</p><p>Lunn and Wang (2008) provided a detailed review of clinical features, molecular pathogenesis, and therapeutic strategies for SMA. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Many groups observed the occurrence of different SMA subtypes within the same family, suggesting different manifestations of a single disease entity. Ghetti et al. (1971) reported that in many families 'malignant' Werdnig-Hoffmann disease coexisted with the Werdnig-Hoffmann disease with a prolonged course, the Wohlfart-Kugelberg-Welander disease with infantile onset, and the Wohlfart-Kugelberg-Welander disease with juvenile onset. Pearn et al. (1973) suggested that both the age of onset and the age of death were important in delineating this disorder and that therefore it should be called the infantile acute form of Werdnig and Hoffmann. </p><p>Feingold et al. (1977) referred to 'acute' and 'chronic' forms of infantile spinal muscular atrophy. </p><p>Zerres and Grimm (1983) presented a pedigree in which 2 males died at the age of 13 and 19 months, respectively, of the Werdnig-Hoffmann type of spinal muscular atrophy; a son and daughter of a great-aunt of theirs died at the age of 6 and 3.4 years, respectively, of Werdnig-Hoffmann disease, and a 59-year-old son of a great-uncle of theirs suffered from SMA of the Kugelberg-Welander type, with onset at age 12 years. </p><p>Thomas and Dubowitz (1994) found a correlation between age of onset and age of death in 2 cohorts of patients with spinal muscular atrophy, consisting of 36 and 70 patients, respectively. In one cohort, the shortest survival was 5 hours, and the longest was 19 months. In the other cohort, the mean age of onset was 1.6 months and the mean age of death was 9.6 months. The data further suggested that patients with onset before 2 months of age have a poor prognosis, with earlier death than those with slightly later onset who still fulfill the diagnostic criteria for type I. </p><p>Lumaka et al. (2009) reported a boy from central Africa with classic type 1 SMA confirmed by genetic analysis. He presented at birth with axial hypotonia and poor spontaneous movements. By age 5.5 months, he had extreme hypotonia, was unable to hold his head up, and showed psychomotor delay. He had joint laxity, severe proximal muscle weakness, umbilical hernia, atrial septal defect, and recurrent pulmonary infections resulting in death by age 10 months. EMG studies showed evidence for an alpha-motor neuron defect. An older brother who died at 10 months was reportedly similarly affected. Lumaka et al. (2009) noted that this was the first documented report of SMA type 1 in central Africa. </p><p><strong><em>Pathologic Findings</em></strong></p><p>
|
|
Muscle biopsies of infantile spinal muscular atrophy demonstrate large numbers of round atrophic fibers and clumps of hypertrophic fibers that are type 1 by the ATPase reaction. Soubrouillard et al. (1995) performed immunohistochemical analyses of biopsied skeletal muscle from 23 cases of infantile SMA to determine the expression of developmentally regulated cytoskeletal components, including desmin (125660), NCAM (116930), vimentin (193060), and embryonic and fetal forms of the myosin heavy chain. Strong NCAM and developmental myosin heavy chain expression was present in atrophic fibers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By analysis of a questionnaire-based retrospective study of 65 patients with SMA type 1, Rudnik-Schoneborn et al. (2008) concluded that congenital heart defects may result from severe SMN deficiency. Among these patients, 4 (6%) had 1 copy of SMN2, 56 (86%) had 2 copies, and 5 (8%) had 3 copies. Three (75%) of the 4 patients with a single SMN2 copy had congenital SMA with atrial or ventricular septal defects. Six of the 56 patients with 2 copies of SMN2 showed minor cardiac anomalies that resolved spontaneously, including a patent foramen ovale (PFO) in 4 infants, associated with a hypertrophic septum in 1, a patent ductus arteriosus (PDA) in 1 patient, and a PDA combined with a PFO in another patient. A small apical ventricular septal defect along with PDA was seen in 1 patient with classic SMA I who died at 11 months. She was the child of consanguineous parents who had lost 4 other children due to alleged sudden infant death syndrome. No cardiac malformation was documented in the 5 patients with 3 SMN2 copies. In a literature review, Rudnik-Schoneborn et al. (2008) noted that most reported SMA patients with heart defects had a severe disease course, congenital or prenatal onset, congenital contractures, respiratory distress from birth, and a very short life span, most likely associated with only 1 SMN2 copy. </p><p>Ebert et al. (2009) reported the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy type 1. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. Ebert et al. (2009) stated that this was the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. Ebert et al. (2009) suggested that since animal models for SMA1 are nonviable, the generation of these pluripotent stem cells would allow more detailed studies of the pathophysiology of SMA1 in the motor neuron. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Brandt (1949) reported a large study of familial infantile progressive muscular atrophy involving 112 cases in 70 families. Segregation analysis yielded results consistent with autosomal recessive inheritance. Almost 6% of the parents were consanguineous, a value 8 times that in controls.</p><p>Marquardt et al. (1962), among others, described the disorder in twins. Hogenhuis et al. (1967) reported studies of a Chinese family in which 4 of 8 sibs succumbed to Werdnig-Hoffmann disease. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>See 600354 for details on the molecular diagnosis of SMA.</p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
|
|
Daniels et al. (1992) and Melki et al. (1992) demonstrated the feasibility of prenatal diagnosis of SMA by the linkage principle. </p><p>Wirth et al. (1995) presented their experience with 109 prenatal diagnoses performed in 91 families at risk of SMA by use of polymorphic microsatellites in the region 5q11.2-q13.3. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be at more than 99% risk of developing the disease, while in 7 additional pregnancies no exact prediction could be made due to a recombination event in 1 parental haplotype. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Oprea et al. (2008) discovered that unaffected SMN1-deleted females exhibit significantly higher expression of plastin-3 (PLS3; 300131) than their SMA-affected counterparts. The authors demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN downregulation in motor neurons of SMA mouse embryos and in zebrafish. Oprea et al. (2008) concluded that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.</p><p>Wen et al. (2010) described a potential link between stathmin (STMN1; 151442) and microtubule defects in SMA. Stathmin was identified by screening Smn-knockdown NSC34 cells through proteomics analysis. Stathmin was aberrantly upregulated in vitro and in vivo, leading to a decreased level of polymerized tubulin, which was correlated with disease severity. Reduced microtubule densities and beta-3-tubulin (TUBB3; 602661) levels in distal axons of affected SMA-like mice and an impaired microtubule network in Smn-deficient cells were observed, suggesting an involvement of stathmin in those microtubule defects. Furthermore, knockdown of stathmin restored the microtubule network defects of Smn-deficient cells, promoted axon outgrowth, and reduced the defect in mitochondria transport in SMA-like motor neurons. The authors concluded that aberrant stathmin levels may play a detrimental role in SMA. </p><p>Kye et al. (2014) found that expression of microRNA-183 (MIR183; 611608), but not its primary transcript, was increased in Smn-knockdown rat primary neurons, concomitant with impaired axonal growth, impaired local translation of Mtor (601231) in neurites, and reduced Mtor pathway-dependent neurite protein synthesis. Mir183 was also elevated in SMA model mice and in SMA patient-derived fibroblasts. Codepletion of Mir183 and Smn in rat neurons rescued the axonal phenotype and increased Mtor expression in neurites. Kye et al. (2014) identified an Mir183-binding site in the 3-prime UTR of the Mtor transcript, and Mir183 bound directly to this site and inhibited Mtor translation. Inhibition of Mir183 in vivo partly alleviated the disease phenotype in SMA model mice. Kye et al. (2014) concluded that axonal MIR183 and the MTOR pathway contribute to SMA pathology. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Chang et al. (2001) reported results suggesting that sodium butyrate may be helpful in the treatment of SMA. They found that this agent increased the amount of exon 7-containing SMN protein in lymphoid cell lines from SMA patients by changing the alternative splicing pattern of exon 7 in the SMN2 gene. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all 3 types of SMA-like mice. </p><p>Brichta et al. (2003) showed that in fibroblast cultures derived from SMA patients treated with therapeutic doses of valproic acid (VPA), the level of full-length SMN2 mRNA/protein increased 2- to 4-fold. This upregulation of SMN was most likely attributable to increased levels of HTRA2-beta-1 (see 606441) as well as to SMN gene transcription activation. VPA was also able to increase SMN protein levels through transcription activation in organotypic hippocampal rat brain slices. Additionally, valproic acid increased the expression of other serine-arginine (SR) family proteins, which may have important implications for other disorders affected by alternative splicing. </p><p>In a study of valproic acid (VPA) treatment in 10 SMA carriers and 20 patients with SMA1, SMA2, or SMA3, Brichta et al. (2006) found that VPA increased peripheral blood full-length SMN mRNA and protein levels in 7 carriers, increased full-length SMN2 mRNA in 7 patients, and left full-length SMN2 mRNA levels unchanged or decreased in 13 patients. The effect on protein levels in carriers was more pronounced than on mRNA levels, and the variability in augmentation among carriers and patients suggested to the authors that valproic acid interferes with transcription of genes encoding translation factors or regulates translation or SMN protein stability. </p><p>In fibroblast cultures from patients with SMA I, SMA II, or SMA III, Andreassi et al. (2004) found a significant increase in SMN2 gene expression (increase in SMN2 transcripts of 50 to 160% in SMA1, and of 80 to 400% in SMA2 and SMA3) and a more moderate increase in SMN protein expression in response to treatment with 4-phenylbutyrate (PBA). PBA treatment also resulted in an increase in the number of SMN-containing nuclear structures (GEMS). The authors suggested a potential use for PBA in treatment of various types of SMA. </p><p>Grzeschik et al. (2005) reported that cultured lymphocytes from patients with SMA showed increased production of the full-length SMN mRNA and protein in response to treatment with hydroxyurea. The findings suggested that hydroxyurea promoted inclusion of exon 7 during SMN2 transcription. </p><p>In a review of questionnaire-based data on 143 SMA patients, Oskoui et al. (2007) found that patients born from 1995 to 2006 had a 70% reduction in the risk of death compared to patients born from 1980 to 1994. However, when controlling for demographic and clinical care variables, the association was no longer significant. Treatment with ventilation for more than 16 hours per day, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feedings showed a significant effect in reducing the risk of death. An amino acid diet had no significant effect on survival. Oskoui et al. (2007) concluded that the increased use of specific proactive management tools has been successful in enhancing survival of patients with SMA. </p><p>Angelozzi et al. (2008) found that salbutamol increased full-length SMN2 mRNA transcript levels in fibroblasts derived from patients with SMA I, II, and III. The maximum increase (over 200%) was observed after 30 to 60 minutes. This rapid rise correlated with decreased levels of SMN2 with deletion of exon 7. Salbutamol treatment also resulted in increased SMN protein levels and nuclear gems. </p><p>Yuo et al. (2008) found that treatment of SMA lymphoid cell lines with an Na+/H+ exchange inhibitor resulted in increased expression of SMN2 mRNA with exon 7 and increased SMN protein production in SMA cells. The underlying mechanism appeared to be upregulation of the splicing factor SRp20 (603364) in the nucleus. The findings were consistent with an effect of cellular pH on SMN splicing. </p><p>Ebert et al. (2009) reported the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy type 1. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. Ebert et al. (2009) stated that this was the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. Ebert et al. (2009) suggested that since animal models for SMA1 are nonviable, the generation of these pluripotent stem cells would allow more detailed studies of the pathophysiology of SMA1 in the motor neuron. </p><p>Through chemical screening and optimization, Naryshkin et al. (2014) identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 mRNA with high selectivity. Administration of these compounds to delta-7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By homozygosity testing of 4 consanguineous families with SMA type I, Gilliam et al. (1990) linked the disorder to chromosome 5q11.2-q13.3, the same region to which the more chronic forms SMA II and SMA III had been mapped. </p><p>Melki et al. (1990) independently demonstrated that SMA type I, like types II and III, was linked to markers at chromosome 5q12-q14. By in situ hybridization of 2 markers closely flanking the SMA I gene, Mattei et al. (1991) refined the assignment to 5q12-q13.3. </p><p>Daniels et al. (1992) used in situ hybridization to refine the mapping of SMA I to 5q12.2-q13 near marker D5S6. Brzustowicz et al. (1992) identified 2 flanking loci, MAP1B (157129) and D5S6, which are separated by an interval of approximately 2 cM. Wirth et al. (1993) narrowed the assignment to a region of about 4 cM and defined a new proximal genetic border by the locus D5S125. The closest marker on the distal side of SMA was found to be MAP1B, which has its 5-prime end directed toward the centromere. </p><p>Lien et al. (1991) used a polyclonal antiserum directed against the C-terminal domain of dystrophin (300377) to isolate a cDNA encoding an antigenically cross-reactive protein. Physical mapping of this gene placed it at 5q13 in close proximity to the SMA locus. A genetic linkage analysis of SMA families using a dinucleotide repeat polymorphism related to the dystrophin-like gene showed tight linkage to SMA mutations. The brain-specific expression of the gene likewise suggested possible association with SMA.</p><p>By a combination of genetic and physical mapping, Melki et al. (1994) constructed a yeast artificial chromosome (YAC) contig of the 5q13 region spanning the SMN disease locus and showing the presence of low copy repeats. Analysis of allele segregation at the closest genetic loci in 201 SMA families demonstrated inherited and de novo deletions in 9 unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18% of SMA type I patients by the observation of marked deficiency of heterozygosity for the loci studied. The results indicated that deletion events were statistically associated with the severe form of spinal muscular atrophy. </p><p>Thompson et al. (1995) identified several coding sequences unique to the SMA region. A genomic fragment detected by 1 cDNA was homozygously deleted in 17 of 29 (58%) type I SMA patients. Only 2 of 235 unaffected controls showed the deletion, and both were carriers of the disease. These data suggested that deletion of at least part of this novel gene is directly related to the phenotype of SMA. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Biros and Forrest (1999), Wirth (2000), and Ogino and Wilson (2004) provided reviews of the complex molecular basis of SMA. SMN1 and SMN2 lie within the telomeric and centromeric halves, respectively, of a large inverted repeat on chromosome 5q. The coding sequence of SMN2 differs from that of SMN1 by a single nucleotide in exon 7 (840C-T), which results in decreased transcription and deficiency of the normal stable SMN protein. Approximately 94% of individuals with SMA lack both copies of SMN1 exon 7, resulting in substantial loss of the protein. Loss of exon 7 can result from deletion or the 840C-T change, in which SMN1 is essentially converted to SMN2 (gene conversion) (Lorson et al., 1999). Loss of SMN1 can also occur by other mechanisms, such as large deletions or point mutations. Most of the SMN protein is derived from the SMN1 gene; however, the SMN2 gene can contribute a small amount of SMN protein, thus modifying the genotype. For a detailed discussion of the molecular genetics of SMA, see 600354. </p><p>Lefebvre et al. (1995) identified the SMN gene, which they termed 'survival motor neuron,' within the SMA candidate region on chromosome 5q13, and demonstrated deletion or disruption of the gene in 226 of 229 patients with SMA. </p><p>In a separate publication accompanying that by Lefebvre et al. (1995), Roy et al. (1995) identified a different gene on chromosome 5q13.1, neuronal apoptosis inhibitory protein (NAIP; 600355). They found that the first 2 coding exons of this gene were deleted in approximately 67% of type I SMA chromosomes compared with 2% of non-SMA chromosomes, and reverse transcriptase-PCR analysis revealed internally deleted and mutated forms of the NAIP transcript in type I SMA individuals and not in unaffected individuals. Roy et al. (1995) suggested that mutations in the NAIP locus resulted in a failure of a normally occurring inhibition of motor neuron apoptosis that occurs during development, thus contributing to the SMA phenotype. In a discussion of these seemingly discordant findings, Lewin (1995) suggested that a mutation in either of the 2 genes could result in SMA or that a mutation in both genes was necessary for the disease. Gilliam (1995) discussed the evidence that either the NAIP gene or the SMN gene, or perhaps both, are involved in the causation of SMA. </p><p>Matthijs et al. (1996) identified homozygous deletion of exon 7 of the SMN1 gene in 34 of 38 patients with SMA. Of these 34 patients, the deletion was associated with homozygous deletion of exon 8 in 31 patients and with heterozygous deletion of exon 8 in 2 patients; both copies of exon 8 were present in 1 patient. In 1 family, a normal father of the proband had only 1 copy of the SMN gene and lacked both copies of the SMN2 gene, showing that a reduction of the total number of SMN genes to a single SMN copy is compatible with normal life. In another family, a de novo deletion of a paternal SMN2 gene was found in a normal sister of a girl with SMA I. Matthijs et al. (1996) suggested that 'this region of chromosome 5q shows some special characteristics which should lead to caution' in the molecular diagnosis of SMA I. Deletions of the SMN gene were not found in 4 of the patients with SMA I. </p><p>Hahnen et al. (1996) reported molecular analysis of 42 SMA patients who carried homozygous deletions of exon 7 but not of exon 8 in the SMN1 gene. Additional homozygous deletions of exon 8 in the SMN2 gene were found in 2 of the patients. By a simple PCR test, Hahnen et al. (1996) demonstrated the existence of hybrid SMN genes (i.e., genes composed of both the centromeric SMN2 and the telomeric SMN1). They reported a high frequency of hybrid SMN genes in SMA patients with Czech or Polish background. Hahnen et al. (1996) identified a single haplotype for half of the hybrid genes analyzed, suggesting that in these cases the SMA chromosomes shared a common origin. </p><p>Alias et al. (2009) found homozygous absence of SMN1 exons 7 and 8 in 671 (90%) of 745 Spanish SMA patients. Thirty-seven patients (5%) had homozygous absence of exon 7 but not exon 8, due to the presence of hybrid genes. The majority of the remaining 5% of patients had smaller deletions or point mutations. However, only 1 mutant allele was identified in 7 (0.9%) patients. Data stratification by SMA type showed that females had a significantly higher frequency of type I SMA compared to males. </p><p><strong><em>Modifying Factors</em></strong></p><p>
|
|
Stratigopoulos et al. (2010) evaluated blood levels of PLS3 (300131) mRNA transcripts in 88 patients with SMA, including 29 males under age 11 years, 12 males over age 11, 29 prepubertal girls, and 18 postpubertal girls in an attempt to examine whether PLS3 was a modifier of the phenotype. PLS3 expression was decreased in the older patients of both sexes. However, expression correlated with phenotype only in postpubertal girls: expression was greatest in those with SMA type III, intermediate in those with SMA type II, and lowest in those with SMA type I, and correlated with residual motor function as well as SMN2 copy number. Stratigopoulos et al. (2010) concluded that the PLS3 gene may be an age- and/or puberty-specific and sex-specific modifier of SMA. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>For a detailed discussion of genotype/phenotype correlations in spinal muscular atrophy, see 600354.</p><p>Burlet et al. (1996) found large-scale deletions involving both the SMN gene and its upstream (C212-C272) and downstream (NAIP) flanking markers in 43% of 106 unrelated SMA patients. However, they noted that smaller rearrangements can still result in disease, since 27% of patients with severe disease lacked only the SMN gene. They also pointed out that deletion of the SMN gene may produce mild disease and referred to an article by Cobben et al. (l995) in which deletions of the SMN gene were found in unaffected sibs of patients with SMA. Burlet et al. (1996) suggested that other genetic mechanisms might be involved in the variable clinical expression of the disease. </p><p>Using pulsed field gel electrophoresis to map deletions in the SMN gene, Campbell et al. (1997) found that mutations in SMA types II and III, previously classed as deletions, were in fact due to gene-conversion events in which the telomeric SMN1 was replaced by its centromeric counterpart, SMN2. This resulted in a greater number of SMN2 copies in type II and type III patients compared with type I patients and enabled a genotype/phenotype correlation to be made. Campbell et al. (1997) also demonstrated individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explained why no consensus map of this region of 5q had been produced. They suggested that this DNA variation may be due to a 'midisatellite' array, which would promote the observed high deletion and gene conversion rate. Burghes (1997) discussed the significance of the findings of Campbell et al. (1997) and presented a model (Figure 3) of alleles present in the normal population and in severe and mild forms of SMA. Campbell et al. (1997), Burghes (1997) raised the question of whether the centromeric SMN2 gene might be activated to compensate for the deficiency of SMN1 as a therapeutic strategy in SMA. </p><p>Samilchuk et al. (1996) carried out deletion analysis of the SMN and NAIP genes in 11 cases of type I SMA and 4 cases of type II SMA. The patients were of Kuwaiti origin. They also analyzed samples from 41 healthy relatives of these patients and 44 control individuals of Arab origin. They found homozygous deletions of exons 7 and 8 of the SMN gene in all SMA patients studied. Exon 5 of the NAIP gene was homozygously absent in all type I SMA patients, but was retained in the type II patients. Among relatives, they identified 1 mother was had homozygous deletion of NAIP. All of the control individuals had normal SMN and NAIP. Samilchuk et al. (1996) concluded that the incidence of NAIP deletion is much higher in the clinically more severe cases (type I SMA) than in the milder forms, and all of the type II SMA patients in their study had at least one copy of the intact NAIP gene. </p><p>Somerville et al. (1997) presented a compilation of genotypes for the SMN1 and NAIP genes from their own laboratory and those of others as reported in the literature. Bayesian analyses were used to generate probabilities for SMA when deletions were present or absent in SMN1. They found that when the SMN1 exon 7 was deleted, the probability of SMA could reach greater than 98% in some populations, and when SMN1 was present, the probability of SMA was approximately 17 times less than the prior population risk. Deletion of NAIP exon 5, as well as SMN1 exon 7, was associated with a 5-fold increased risk of type I SMA. Case studies were used to illustrate differing disease risks for pre- and postnatal testing, depending on the presence of information about clinical status or molecular results. These analyses demonstrated that deletion screening of candidate genes can be a powerful tool in the diagnosis of SMA. </p><p>Novelli et al. (1997) investigated the effects of gender on the association between NAIP gene deletion and disease severity in SMA. NAIP deletions were screened in 197 SMA patients lacking SMN; the results obtained were correlated with disease severity in male and female samples separately. No significant relationship between deletion size and clinical phenotype was observed among male patients, whereas in females the absence of NAIP was strongly associated with a severe phenotype (p less than 0.0001). SMA I was found in 75.6% of females and only 52.5% of males lacking NAIP. These results provided a possible molecular explanation for the sex-dependent phenotypic variation observed in SMA patients. </p><p>Using comparative genomics to screen for modifying factors in SMA among sequences evolutionarily conserved between mouse and human, Scharf et al. (1998) identified a novel transcript, H4F5 (603011), which lay closer to SMN1 than any previously identified gene in the region. They found that a multicopy microsatellite marker that was deleted in more than 90% of type I SMA chromosomes was embedded in an intron of the SMN1 gene, indicating that H4F5 may also be deleted in type I SMA, and thus was a candidate phenotypic modifier for SMA. In comparison with the high rate of H4F5 deletions in type I SMA, Scharf et al. (1998) found that the deletion frequency in type II SMA chromosomes was between that of type I and control chromosomes, whereas the frequency in type III chromosomes was only slightly higher than in controls. </p><p>Jedrzejowska et al. (2008) reported 3 unrelated families with asymptomatic carriers of a biallelic deletion of the SMN1 gene. In the first family, the biallelic deletion was found in 3 sibs: 2 affected brothers with SMA3 and a 25-year-old asymptomatic sister. All of them had 4 copies of the SMN2 gene. In the second family, 4 sibs were affected, 3 with SMA2 and 1 with SMA3, and each had 3 copies of SMN2. The clinically asymptomatic 47-year-old father had the biallelic deletion and 4 copies of SMN2. In the third family, the biallelic SMN1 deletion was found in a girl affected with SMA1 and in her healthy 53-year-old father who had 5 copies of SMN2. The findings again confirmed that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but also suggested that other factors play a role in disease modification. </p><p>Rudnik-Schoneborn et al. (2009) reviewed the clinical features of 66 German patients with SMA type 1 caused by homozygous deletion of the SMN1 gene. Reduced fetal movements were recorded in 33% of pregnancies. Sixteen (24%) patients showed onset of weakness in the first week of life; the overall mean age at death was 9 months. Four (6.1%) patients with 1 SMN2 gene copy had severe SMA type '0' with joint contractures and respiratory distress from birth. All died within a few months of age. Among the 57 (86.3%) patients with 2 SMN2 copies, the mean age at onset was 1.3 months, and the mean age at disease endpoint (death or need for permanent ventilation) was 7.8 months. Among the 5 (7.6%) of patients with 3 SMN2 copies, the mean age at onset was 3.4 months and the mean age at endpoint was 28.9 months (range, 10 to 55 months). Rudnik-Schoneborn et al. (2009) noted that much of the observed clinical variability in SMA type 1 likely depends on the number of SMN2 copies, and suggested that the SMN2 copy number should be considered in clinical trials. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Czeizel and Hamula (1989) and Czeizel (1991) estimated the prevalence of Werdnig-Hoffmann disease in Hungary to be 1 per 10,000 live births. The occurrence in sibs was 32%, a figure considered consistent with autosomal recessive inheritance complicated by greater ascertainment of families with more than 1 affected child. </p><p>From an epidemiologic study of acute and chronic childhood SMA in Poland, Spiegler et al. (1990) cited a frequency of 1.026 cases per 10,000, a gene frequency of 0.01428, and a carrier frequency of 1 in 35. Spiegler et al. (1990) reviewed various other reports on the frequency of SMA. For an 8-year period (1980-1987) in the State of North Dakota, Burd et al. (1991) found an incidence of 1 in 6,720 births (14 in 94,092). In an Italian population, Mostacciuolo et al. (1992) found an overall prevalence at birth for SMA types I, II, and III to be 7.8 in 100,000 live births. Type I alone accounted for 4.1 in 100,000 live births. Assuming that the 3 types are clinical manifestations of allelic mutations, the locus mutation rate would be about 70 x 10(-6) and the frequency of heterozygotes about 1 in 57. </p><p>Wilmshurst et al. (2002) performed DNA studies in 30 unrelated and racially diverse patients with SMA residing in the Western Cape of South Africa. Four had SMA type I, 16 had type II, and 10 had type III. All patients were found to be homozygous for the loss of either exon 7 or exons 7 and 8 of the SMN1 gene. Thus, all patients from the Western Cape, which included 12 black South Africans, were no different genetically or phenotypically from the internationally recognized form of typical SMA. </p><p>Zaldivar et al. (2005) found that the incidence of SMA type I in Cuba was 3.53 per 100,000 live births. When the population was classified according to self-reported ethnicity, the incidence was 8 per 100,000 for whites, 0.89 per 100,000 for blacks, and 0.96 per 100,000 for those of mixed ethnicity. Zaldivar et al. (2005) concluded that SMA I may occur less frequently in those of African ancestry. </p><p>In a detailed review, Lunn and Wang (2008) stated that the incidence of SMA was 1 in 10,000 livebirths and that the carrier frequency was 1 in 50. In a reply, Wilson and Ogino (2008) stated that carrier testing had revealed a carried frequency of 1 in 38, which extrapolates to an incidence of 1 in 6,000 livebirths under Hardy-Weinberg equilibrium. Wilson and Ogino (2008) postulated that the numerical differences could be due to embryonic lethality or clinically atypical SMA. </p><p>Hendrickson et al. (2009) genotyped more than 1,000 specimens from various ethnic groups using a quantitative real-time PCR assay specific for the 840C-T change in exon 7, which results in loss of SMN1. The observed 1-copy SMN1 carrier rate was 1 in 37 (2.7%) among Caucasians, 1 in 46 (2.2%) among Ashkenazi Jews, 1 in 56 (1.8%) 56 among Asians, 1 in 91 (1.1%) among African Americans, and 1 in 125 (0.8%) among Hispanics. In all groups except African Americans the 2-copy genotype was the most common. However, African American specimens had an unusually high frequency of alleles with multiple copies of SMN1 (27% compared to 3.3-8.1%). The authors noted that alleles with increased numbers of SMN1 copies increase the relative risk of being a carrier due to the inability of many methods to detect the rare SMN1 genotype consisting of 1 allele with zero copies and the other allele with 2 or more copies. </p><p>Using denaturing high-performance liquid chromatography (DHPLC) as a screening tool to determine SMN copy number, Sheng-Yuan et al. (2010) found a heterozygous deletion of SMN1 exon 7 in 41 (2.39%) of 1,712 cord blood samples from Chinese infants, indicating a carrier state. Thirteen different genotypic groups characterized by SMN1:SMN2 copy number ratio were identified overall. Carrier genotypes were similar among 25 core families with the disorder, with the '1+0' SMN1 genotype accounting for 90.9% of carriers, although 2 of 44 parents had the rare '2+0' genotype. Sheng-Yuan et al. (2010) developed an assay based on reverse dot blot for rapid genotyping of exon 7 deletional SMA. Sheng-Yuan et al. (2010) concluded that the carrier rate of SMA in China is 1 in 42 and that approximately 2,306 newborns are affected each year. </p><p>Chong et al. (2011) identified a shared haplotype encompassing the SMN1/SMN2 genes in a Hutterite patient from South Dakota and 3 Hutterite patients from Montana. An 8-generation pedigree connected these 4 individuals to their most recent common ancestors, who were a couple born in the 1790s. All 4 patients carried zero copies of SMN1 and 4 copies of SMN2, indicating that the haplotype carrying the deletion of SMN1 also carries 2 copies of SMN2. The carrier frequency for this haplotype was 12.9% in South Dakota Hutterites. The phenotypic expression of this phenotype was relatively mild, and 1 asymptomatic homozygous adult was identified. Chong et al. (2011) identified a 26-SNP haplotype that could be used for screening in this population. </p><p>Among 23,127 ethnically diverse individuals screened for SMA1 carrier status, Lazarin et al. (2013) identified 405 carriers (1.8%), for an estimated carrier frequency of approximately 1 in 57. Fifteen 'carrier couples' were identified. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Becker (1964) suggested an allelic model for the clinically distinct subtypes of SMA: 3 or more normal alleles (a, a', a'') in addition to the pathologic gene a(+). The genotype a'a(+) was thought to lead to Kugelberg-Welander phenotype and the a''a(+) genotype to the Werdnig-Hoffmann phenotype. Bouwsma and Leschot (1986) extended the allele hypothesis of Becker. They presented clinical and genetic findings in 18 patients from 7 pedigrees showing an unusual genetic pattern not consistent with simple autosomal recessive inheritance. In 6 of the 7 pedigrees, different types of SMA were present. However, Muller et al. (1992) presented evidence rejecting the Becker hypothesis. In a sample of 4 sibships in which both SMA type II and SMA type III occurred, the segregation of linked markers indicated that the same allele was involved. The finding suggested that other factors, genetic or environmental, must determine disease severity in SMA. </p><p>Kleyn et al. (1991) excluded both the HEXB locus (606873) and the GM2-activator protein locus (GM2A; 613109), both of which are located on chromosome 5, as the site of the mutation in SMA. Recombination between HEXB and SMA eliminated this enzyme as a candidate site. Furthermore, the gene encoding the activator protein was found to map distal to the SMA I locus (Heng et al., 1993). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Exclusion of the Wobbler Mouse and a Canine Model</em></strong></p><p>
|
|
Kaupmann et al. (1992) mapped the 'wobbler' locus (wr) (see 614633) to proximal mouse chromosome 11. The wobbler mouse (genotype wr/wr) shows motoneuron disease and gonadal dysfunction. Kaupmann et al. (1992) stated that the wobbler was an unlikely model for human SMA because it shows also a striking spermiogenesis defect which has not been reported for male SMA patients who have reached adolescence. </p><p>Des Portes et al. (1994) also mapped the mouse 'wobbler' mutation to mouse chromosome 11, about 1 cM from the glutamine synthetase gene (138290); several crossovers excluded glutamine synthetase from being a candidate gene for the wobbler mutation. The murine equivalent of the human 5q region is mainly situated on chromosomes 13 and 11, and the closest published marker for human spinal muscular atrophy, D5S39, was mapped to mouse chromosome 13. Thus, it seemed unlikely that the wobbler mutation and the common human spinal muscular atrophies were genetically identical, despite their similar phenotype. </p><p>Blazej et al. (1998) concluded that autosomal dominant canine spinal muscular atrophy, which has pathologic and clinical features similar to various forms of human motor neuron disease, was molecularly distinct from human spinal muscular atrophy. They studied the canine SMN gene in affected and unaffected dogs and found no germline mutations in the SMN gene in affected dogs. Analysis of a panel of canine/rodent hybrid cell lines revealed that the SMN gene did not map to the same chromosome in the dog as did the canine spinal muscular atrophy. </p><p><strong><em>Other Animal Models</em></strong></p><p>
|
|
Hsieh-Li et al. (2000) produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2 (601627). Smn -/- mice died during the periimplantation stage. In contrast, transgenic mice harboring SMN2 in the Smn -/- background showed pathologic changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathologic changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. The results demonstrated that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn -/- SMN2 mice reflected those seen in SMA patients, thus providing a mouse model for that disease. </p><p>Frugier et al. (2000) used the Cre/loxP recombination system and a neuron-specific promoter to generate transgenic mice with selective expression in neural tissue of an SMN construct missing exon 7. Unlike mice missing SMN exon 7 in all tissues (an embryonic lethal phenotype), those with a neuron-specific defect displayed a severe motor deficit with tremors. The mutated SMN protein lacked the normal C terminus and was dramatically reduced in motor neuron nuclei. Histologic analysis revealed a lack of GEMS (gemini of coiled bodies, which are normal nuclear structures) and the presence of large aggregates of coilin, a coiled body-specific protein (600272). The authors concluded that the lack of nuclear targeting of SMN is the biochemical defect in SMA, which leads to muscle denervation of neurogenic origin. </p><p>Studying Brown-Swiss cattle, Medugorac et al. (2003) mapped the bovine spinal muscular atrophy locus to chromosome 24. Before performing a genomewide linkage analysis, they investigated 2 candidate chromosome segments: the proximal part of bovine chromosome 20 and the complete bovine chromosome 29. These regions are orthologous to human chromosome segments responsible for SMA1 and SMA with respiratory distress (SMARD1; 604320), respectively. No abnormalities were found in these regions. The linkage region on chromosome 24 contains the homolog of the BCL2 gene (151430) on human chromosome 18q. Medugorac et al. (2003) suggested that the gene encoding the apoptosis-inhibiting protein BCL2 is a promising candidate for bovine SMA and that the disorder in Brown-Swiss cattle offers an attractive animal model for a better understanding of human SMA and for a probable antiapoptotic synergy of SMN-BCL2 aggregates in mammals. </p><p>Chan et al. (2003) isolated a Drosophila smn mutant with point mutations in the smn gene similar to those found in SMA patients. Zygotic smn mutant animals showed abnormal motor behavior; smn gene activity was required in both neurons and muscle to alleviate this phenotype. Excitatory postsynaptic currents were reduced while synaptic motor neuron boutons were disorganized in mutants, indicating defects at the neuromuscular junction. Clustering of a neurotransmitter receptor subunit in the muscle at the neuromuscular junction was also severely reduced. </p><p>In a mouse model of SMA, Kariya et al. (2008) demonstrated that the earliest structural defects of the disorder appeared in the distal muscles and involved the neuromuscular synapse even before the appearance of overt symptoms. Insufficient SMN protein arrested the postnatal development of the neuromuscular junction (NMJ), impairing the maturation of postsynaptic acetylcholine receptor (AChR) clusters. Presynaptic defects at the distal ends of alpha-motor neurons included poor terminal arborization, intermediate filament aggregates, and misplaced synaptic vesicles. These defects were reflected in functional deficits at the NMJ characterized by intermittent neurotransmission failures. Kariya et al. (2008) suggested that SMA might best be described as a NMJ synaptopathy. </p><p>In severe SMA mice (Smn -/-;SMN2 +/+) Gavrilina et al. (2008) found that transgenic embryonic expression of full-length SMN under the prion (176640) promoter in brain and spinal cord neurons rescued the phenotype. Mice homozygous for the transgene survived for an average of 210 days, compared to 4.6 days in control SMA mice, and lumbar motor neuron root counts in the transgenic mice were normal. High levels of SMN in neurons were observed at embryonic day 15. In contrast, transgenic expression of SMN solely in skeletal muscle using the human skeletal actin promoter resulted in no improvement of the SMA phenotype or extension of survival in SMA mice. However, 1 transgenic strain with high SMN expression in muscle and low SMN expression in brain showed increased survival to 160 days, indicating that even mild neuronal SMN expression can affect the phenotype. Gavrilina et al. (2008) concluded that expression of full-length SMN in neurons can correct the severe SMA phenotype in mice, whereas high SMN levels in mature skeletal muscle alone has no impact. </p><p>Murray et al. (2010) investigated the presymptomatic development of neuromuscular connectivity in differentially vulnerable motor neuron populations in Smn -/-;SMN2 +/+ mice. Reduced Smn levels had no detectable effect on morphologic correlates of presymptomatic development in either vulnerable or stable motor units, indicating that abnormal presymptomatic developmental processes were unlikely to be a prerequisite for subsequent pathologic changes to occur in vivo. Microarray analyses of spinal cord from 2 different severe SMA mouse models demonstrated that only minimal changes in gene expression were present in presymptomatic mice. In contrast, microarray analysis of late-symptomatic spinal cord revealed widespread changes in gene expression, implicating extracellular matrix integrity, growth factor signaling, and myelination pathways in SMA pathogenesis. Murray et al. (2010) suggested that reduced Smn levels induce SMA pathology by instigating rapidly progressive neurodegenerative pathways in lower motor neurons around the time of disease onset, rather than by modulating presymptomatic neurodevelopmental pathways. </p><p>Wishart et al. (2010) showed that reduced levels of Smn led to impaired perinatal brain development in a mouse model of severe SMA. Regionally selective changes in brain morphology were apparent in areas normally associated with higher Smn levels in the healthy postnatal brain, including the hippocampus, and were associated with decreased cell density, reduced cell proliferation, and impaired hippocampal neurogenesis. A comparative proteomics analysis of the hippocampus from SMA and wildtype littermate mice revealed widespread modifications in expression levels of proteins regulating cellular proliferation, migration, and development when Smn levels were reduced. Wishart et al. (2010) proposed roles for SMN protein in brain development and maintenance. </p><p><strong><em>Therapeutic Strategies</em></strong></p><p>
|
|
In SMA-like mouse embryonic fibroblasts and human SMN2-transfected motor neuron cells, Ting et al. (2007) found that sodium vanadate, trichostatin A, and aclarubicin effectively enhanced SMN2 expression by inducing Stat5 (601511) activation. This resulted in enhanced SMN2 promoter activity with an increase in both full-length and deletion exon 7 SMN transcripts in human cells with SMN2. Knockdown of Stat5 expression disrupted the effects of sodium vanadate on SMN2 activation, but did not influence SMN2 splicing, suggesting that Stat5 signaling is involved in SMN2 transcriptional regulation. Constitutive expression of the activated Stat5 mutant Stat5A1*6 profoundly increased the number of nuclear gems in SMA patient lymphocytes and reduced SMA-like motor neuron axon outgrowth defects. </p><p>Narver et al. (2008) found that in a transgenic mouse model of SMA (Smn +/-, SMN2 +/+, SMN-delta-7) early treatment with the HDAC (601241) inhibitor, trichostatin A (TSA), plus nutritional support extended median survival by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after TSA was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe SMA. Narver et al. (2008) concluded that early SMA disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of HDAC inhibitor treatment in human patients. </p><p>Meyer et al. (2009) created an optimal exon 7 inclusion strategy based on a bifunctional U7 snRNA (RNU7-1; 617876) construct that targets the 3-prime part of exon 7 and carries an ESE sequence that can attract stimulatory splice factors. This construct induced nearly complete exon 7 inclusion of an SMN2-reporter in HeLa cells and of endogenous SMN2 in SMA type I patient fibroblasts. Introduction of the U7-ESE-B construct in a severe mouse model of SMA resulted in a clear suppression of disease-associated symptoms, ranging from normal life span with pronounced SMA symptoms to full weight development, muscular function, and ability of female mice to carry to term and feed a normal-sized litter. Exon 7 inclusion in total spinal RNA increased from 26% to 52%, and SMN protein levels increased, albeit only to levels one-fifth of that seen wildtype mice. </p><p>Workman et al. (2009) showed that SMN(A111G), an allele capable of snRNP assembly (A111G; 600354.0015), can rescue mice that lacked Smn and contained either 1 or 2 copies of SMN2 (SMA mice). The correction of SMA in these animals was directly correlated with snRNP assembly activity in spinal cord, as was correction of snRNA levels. These data support snRNP assembly as being the critical function affected in SMA and suggests that the levels of snRNPs are critical to motor neurons. Furthermore, SMN(A111G) could not rescue Smn-null mice without SMN2, suggesting that both SMN(A111G) and SMN from SMN2 may undergo intragenic complementation in vivo to function in heteromeric complexes that have greater function than either allele alone. The oligomer composed of limiting full-length SMN and SMN(A111G) had substantial snRNP assembly activity. The SMN(A2G) (A2G; 600354.0002) and SMN(A111G) alleles in vivo did not complement each other, leading to the possibility that these mutations could affect the same function. </p><p>Mattis et al. (2009) examined the potential therapeutic capabilities of a novel aminoglycoside, TC007. In an intermediate SMA mouse model (Smn -/-; SMN2 +/+; SMN-delta-7), when delivered directly to the central nervous system, TC007 induced SMN in both the brain and spinal cord, significantly increased life span (approximately 30%), and increased ventral horn cell number, consistent with its ability to increase SMN levels in induced pluripotent stem cell-derived human SMA motor neuron cultures. </p><p>Butchbach et al. (2010) tested a series of C5-quinazoline derivatives for their ability to increase SMN expression in vivo. Oral administration of 3 compounds (D152344, D153249, and D156844) to neonatal SMN-delta-7 mice resulted in a dose-dependent increase in Smn promoter activity in the central nervous system. Oral administration of D156844 significantly increased the mean life span of SMN-delta-7 SMA mice by approximately 20-30% when given prior to motor neuron loss. </p><p>Bowerman et al. (2010) showed that Smn depletion led to increased activation of RhoA (165390), a major regulator of actin dynamics, in the spinal cord of an intermediate SMA mouse model. Treating these mice with Y-27632, which inhibits ROCK (601702), a direct downstream effector of RhoA, dramatically improved their survival. This life span rescue was independent of Smn expression and was accompanied by an improvement in the maturation of the neuromuscular junctions and an increase in muscle fiber size in the SMA mice. Bowerman et al. (2010) proposed a role for disruption of actin cytoskeletal dynamics to SMA pathogenesis and suggested that RhoA effectors may be viable targets for therapeutic intervention in the disease. </p><p>Ackermann et al. (2013) found that ubiquitous overexpression of human PLS3 (300131) in mice with a mild SMA phenotype improved motor ability and neuromuscular junction function and moderately increased survival compared with control SMA mice. Expression of PLS3 did not improve the morphology of heart, lung, or intestine, and it did not improve motor ability or survival in mice with a severe SMA phenotype. The authors noted that these findings were consistent with observations in humans showing that PLS3 provides full protection against SMA only in SMN1-deleted individuals with 3 to 4 SMN2 copies, but not in those with 2 SMN2 copies. In mildly affected SMA mice, PLS3 delayed axon pruning until postnatal day 8, which counteracted the poor synaptic activity observed in control SMA mice. F-actin content was increased in presynapses, leading to improved neuromuscular connectivity, restored active zone content of synaptic vesicles, improved organization of the ready releasable vesicle pool, increased endplate and muscle fiber size, and improved neurotransmission. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Brandt (1950); Chow and Nanaka (1978); Cobben et al. (1995);
|
|
Cunningham and Stocks (1978); Daniels et al. (1992); Fried and Mundel
|
|
(1977); Gamstorp (1967); Hanhart (1945); Hausmanowa-Petrusewicz et
|
|
al. (1985); Pascalet-Guidon et al. (1984); Wirth et al. (1997)
|
|
</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">
|
|
Ackermann, B., Krober, S., Torres-Benito, L., Borgmann, A., Peters, M., Barkooie, S. M. H., Tejero, R., Jakubik, M., Schreml, J., Milbradt, J., Wunderlich, T. F., Riessland, M., Tabares, L., Wirth, B.
|
|
<strong>Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality.</strong>
|
|
Hum. Molec. Genet. 22: 1328-1347, 2013.
|
|
|
|
|
|
[PubMed: 23263861]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/dds540]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alias, L., Bernal, S., Fuentes-Prior, P., Barcelo, M. J., Also, E., Martinez-Hernandez, R., Rodriguez-Alvarez, F. J., Martin, Y., Aller, E., Grau, E., Pecina, A., Antinolo, G., Galan, E., Rosa, A. L., Fernandez-Burriel, M., Borrego, S., Millan, J. M., Hernandez-Chico, C., Baiget, M., Tizzano, E. F.
|
|
<strong>Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene.</strong>
|
|
Hum. Genet. 125: 29-39, 2009.
|
|
|
|
|
|
[PubMed: 19050931]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-008-0598-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andreassi, C., Angelozzi, C., Tiziano, F. D., Vitali, T., De Vincenzi, E., Boninsegna, A., Villanova, M., Bertini, E., Pini, A., Neri, G., Brahe, C.
|
|
<strong>Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy.</strong>
|
|
Europ. J. Hum. Genet. 12: 59-65, 2004.
|
|
|
|
|
|
[PubMed: 14560316]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Angelozzi, C., Borgo, F., Tiziano, F. D., Martella, A., Neri, G., Brahe, C.
|
|
<strong>Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells.</strong>
|
|
J. Med. Genet. 45: 29-31, 2008.
|
|
|
|
|
|
[PubMed: 17932121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2007.051177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Becker, P. E.
|
|
<strong>Atrophia musculorum spinalis pseudomyopathica. Hereditaere neurogene proximale Amyotrophie von Kugelberg und Welander.</strong>
|
|
Z. Menschl. Vererb. Konstitutionsl. 37: 193-220, 1964.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Biros, I., Forrest, S.
|
|
<strong>Spinal muscular dystrophy: untangling the knot?</strong>
|
|
J. Med. Genet. 36: 1-8, 1999.
|
|
|
|
|
|
[PubMed: 9950358]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blazej, R. G., Mellersh, C. S., Cork, L. C., Ostrander, E. A.
|
|
<strong>Hereditary canine spinal muscular atrophy is phenotypically similar but molecularly distinct from human spinal muscular atrophy.</strong>
|
|
J. Hered. 89: 531-537, 1998.
|
|
|
|
|
|
[PubMed: 9864863]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/jhered/89.6.531]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bouwsma, G., Leschot, N. J.
|
|
<strong>Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis.</strong>
|
|
Clin. Genet. 30: 145-149, 1986.
|
|
|
|
|
|
[PubMed: 3780029]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1986.tb00586.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowerman, M., Beauvais, A., Anderson, C. L., Kothary, R.
|
|
<strong>Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model.</strong>
|
|
Hum. Molec. Genet. 19: 1468-1478, 2010.
|
|
|
|
|
|
[PubMed: 20097679]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brandt, S.
|
|
<strong>Hereditary factors in infantile progressive muscular atrophy: study of one hundred and twelve cases in seventy families.</strong>
|
|
Am. J. Dis. Child. 78: 226-236, 1949.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brandt, S.
|
|
<strong>Werdnig-Hoffmann's Infantile Progressive Muscular Atrophy: Clinical Aspects, Pathology, Heredity and Relation to Oppenheim's Amyotonia Congenita and other Morbid Conditions with Laxity of Joints or Muscles in Infants.</strong>
|
|
Copenhagen: Munksgaard (pub.) 1950.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F. A., Raschke, H., Blumcke, I., Eyupoglu, I. Y., Wirth, B.
|
|
<strong>Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 12: 2481-2489, 2003.
|
|
|
|
|
|
[PubMed: 12915451]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg256]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brichta, L., Holker, I., Haug, K., Klockgether, T., Wirth, B.
|
|
<strong>In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate.</strong>
|
|
Ann. Neurol. 59: 970-975, 2006.
|
|
|
|
|
|
[PubMed: 16607616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20836]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brzustowicz, L. M., Kleyn, P. W., Boyce, F. M., Lien, L. L., Monaco, A. P., Penchaszadeh, G. K., Das, K., Wang, C. H., Munsat, T. L., Ott, J., Kunkel, L. M., Gilliam, T. C.
|
|
<strong>Fine-mapping of the spinal muscular atrophy locus to a region flanked by MAP1B and D5S6.</strong>
|
|
Genomics 13: 991-998, 1992.
|
|
|
|
|
|
[PubMed: 1505990]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90012-h]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burd, L., Short, S. K., Martsolf, J. T., Nelson, R. A.
|
|
<strong>Prevalence of type I spinal muscular atrophy in North Dakota.</strong>
|
|
Am. J. Med. Genet. 41: 212-215, 1991.
|
|
|
|
|
|
[PubMed: 1785637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320410216]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burghes, A. H. M.
|
|
<strong>When is a deletion not a deletion? When it is converted. (Editorial)</strong>
|
|
Am. J. Hum. Genet. 61: 9-15, 1997.
|
|
|
|
|
|
[PubMed: 9245977]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/513913]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burlet, P., Burglen, L., Clermont, O., Lefebvre, S., Viollet, L., Munnich, A., Melki, J.
|
|
<strong>Large scale deletions of the 5q13 region are specific to Werdnig-Hoffmann disease.</strong>
|
|
J. Med. Genet. 33: 281-283, 1996.
|
|
|
|
|
|
[PubMed: 8730281]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.33.4.281]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Butchbach, M. E. R., Singh, J., Porsteinsdottir, M., Saieva, L., Slominski, E., Thurmond, J., Andresson, T., Zhang, J., Edwards, J. D., Simard, L. R., Pellizzoni, L., Jarecki, J., Burghes, A. H. M., Gurney, M. E.
|
|
<strong>Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 454-467, 2010.
|
|
|
|
|
|
[PubMed: 19897588]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp510]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K.
|
|
<strong>Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.</strong>
|
|
Am. J. Hum. Genet. 61: 40-50, 1997.
|
|
|
|
|
|
[PubMed: 9245983]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/513886]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, Y. B., Miguel-Aliaga, I., Franks, C., Thomas, N., Trulzsch, B., Sattelle, D. B., Davies, K. E., van den Heuvel, M.
|
|
<strong>Neuromuscular defects in a Drosophila survival motor neuron gene mutant.</strong>
|
|
Hum. Molec. Genet. 12: 1367-1376, 2003.
|
|
|
|
|
|
[PubMed: 12783845]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg157]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chang, J.-G., Hsieh-Li, H.-M., Jong, Y.-J., Wang, N. M., Tsai, C.-H., Li, H.
|
|
<strong>Treatment of spinal muscular atrophy by sodium butyrate.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 9808-9813, 2001.
|
|
|
|
|
|
[PubMed: 11504946]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.171105098]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chong, J. X., Oktay, A. A., Dai, Z., Swoboda, K .J., Prior, T. W., Ober, C.
|
|
<strong>A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites.</strong>
|
|
Europ. J. Hum. Genet. 19: 1045-1051, 2011.
|
|
|
|
|
|
[PubMed: 21610747]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2011.85]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chow, S. M., Nanaka, I.
|
|
<strong>Werdnig-Hoffmann disease: proposal of a pathogenetic mechanism.</strong>
|
|
Acta Neuropath. 41: 45-54, 1978.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cobben, J. M., van der Steege, G., Grootscholten, P., de Visser, M., Scheffer, H., Buys, C. H. C. M.
|
|
<strong>Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy.</strong>
|
|
Am. J. Hum. Genet. 57: 805-808, 1995.
|
|
|
|
|
|
[PubMed: 7573039]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cunningham, M., Stocks, J.
|
|
<strong>Werdnig-Hoffmann disease: the effects of intrauterine onset on lung growth.</strong>
|
|
Arch. Dis. Child. 53: 921-925, 1978.
|
|
|
|
|
|
[PubMed: 747396]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.53.12.921]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Czeizel, A., Hamula, J.
|
|
<strong>A Hungarian study on Werdnig-Hoffmann disease.</strong>
|
|
J. Med. Genet. 26: 761-763, 1989.
|
|
|
|
|
|
[PubMed: 2614795]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.26.12.761]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Czeizel, A.
|
|
<strong>High incidence of acute infantile spinal atrophy in Hungary. (Letter)</strong>
|
|
Hum. Genet. 86: 539, 1991.
|
|
|
|
|
|
[PubMed: 2016096]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00194653]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Daniels, R. J., Suthers, G. K., Morrison, K. E., Thomas, N. H., Francis, M. J., Mathew, C. G., Loughlin, S., Heiberg, A., Wood, D., Dubowitz, V., Davies, K. E.
|
|
<strong>Prenatal prediction of spinal muscular atrophy.</strong>
|
|
J. Med. Genet. 29: 165-170, 1992.
|
|
|
|
|
|
[PubMed: 1348091]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.29.3.165]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Daniels, R. J., Thomas, N. H., MacKinnon, R. N., Lehner, T., Ott, J., Flint, T. J., Dubowitz, V., Ignatius, J., Donner, M., Zerres, K., Rietschel, M., Cookson, W. O. C., Brzustowicz, L. M., Gilliam, T. C., Davies, K. E.
|
|
<strong>Linkage analysis of spinal muscular atrophy.</strong>
|
|
Genomics 12: 335-339, 1992.
|
|
|
|
|
|
[PubMed: 1346777]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90382-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
des Portes, V., Coulpier, M., Melki, J., Dreyfus, P. A.
|
|
<strong>Early detection of mouse wobbler mutation: a model of pathological motoneurone death.</strong>
|
|
Neuroreport 5: 1861-1864, 1994.
|
|
|
|
|
|
[PubMed: 7841363]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00001756-199410000-00005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ebert, A. D., Yu, J., Rose, F. F, Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., Svendsen, C. N.
|
|
<strong>Induced pluripotent stem cells from a spinal muscular atrophy patient.</strong>
|
|
Nature 457: 277-280, 2009.
|
|
|
|
|
|
[PubMed: 19098894]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature07677]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Feingold, J., Arthuis, M., Celers, J.
|
|
<strong>Genetique de l'amyotrophie spinale infantile: existence de deux formes autosomiques recessives.</strong>
|
|
Ann. Genet. 20: 19-23, 1977.
|
|
|
|
|
|
[PubMed: 302668]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fried, K., Mundel, G.
|
|
<strong>High incidence of spinal muscular atrophy type I (Werdnig-Hoffmann disease) in the Karaite community in Israel.</strong>
|
|
Clin. Genet. 12: 250-251, 1977.
|
|
|
|
|
|
[PubMed: 912942]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb00934.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frugier, T., Tiziano, F. D., Cifuentes-Diaz, C., Miniou, P., Roblot, N., Dierich, A., Le Meur, M., Melki, J.
|
|
<strong>Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 9: 849-858, 2000.
|
|
|
|
|
|
[PubMed: 10749994]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.5.849]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gamstorp, I.
|
|
<strong>Progressive spinal muscular atrophy with onset in infancy or early childhood.</strong>
|
|
Acta Paediat. Scand. 56: 408-423, 1967.
|
|
|
|
|
|
[PubMed: 6039049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1967.tb15400.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U. R., Morris, G. E., Burghes, A. H. M.
|
|
<strong>Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect.</strong>
|
|
Hum. Molec. Genet. 17: 1063-1075, 2008.
|
|
|
|
|
|
[PubMed: 18178576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm379]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ghetti, B., Amati, A., Turra, M. V., Pacini, A., Del Vecchio, M., Guazzi, G. C.
|
|
<strong>Werdnig-Hoffmann-Wohlfart-Kugelberg-Welander disease: nosological unity and clinical variability in intrafamilial cases.</strong>
|
|
Acta Genet. Med. Gemellol. 20: 43-58, 1971.
|
|
|
|
|
|
[PubMed: 5568110]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1017/s1120962300011707]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gilliam, T. C., Brzustowicz, L. M., Castilla, L. H., Lehner, T., Penchaszadeh, G. K., Daniels, R. J., Byth, B. C., Knowles, J., Hislop, J. E., Shapira, Y., Dubowitz, V., Munsat, T. L., Ott, J., Davies, K. E.
|
|
<strong>Genetic homogeneity between acute and chronic forms of spinal muscular atrophy.</strong>
|
|
Nature 345: 823-825, 1990.
|
|
|
|
|
|
[PubMed: 1972783]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/345823a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gilliam, T. C.
|
|
<strong>Is the spinal muscular atrophy gene found?</strong>
|
|
Nature Med. 1: 124-127, 1995.
|
|
|
|
|
|
[PubMed: 7585007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm0295-124]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grzeschik, S. M., Ganta, M., Prior, T. W., Heavlin, W. D., Wang, C. H.
|
|
<strong>Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells.</strong>
|
|
Ann. Neurol. 58: 194-202, 2005.
|
|
|
|
|
|
[PubMed: 16049920]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20548]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hahnen, E., Schonling, J., Rudnik-Schoneborn, S., Zerres, K., Wirth, B.
|
|
<strong>Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease.</strong>
|
|
Am. J. Hum. Genet. 59: 1057-1065, 1996.
|
|
|
|
|
|
[PubMed: 8900234]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hanhart, E.
|
|
<strong>Die infantile progressive spinale Muskelatrophie (Werdnig-Hoffmann) als einfach-rezessive, subletale Mutation auf Grund von 29 Faellen in 14 Sippen.</strong>
|
|
Helv. Paediat. Acta 1: 110-133, 1945.
|
|
|
|
</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">
|
|
Hendrickson, B. C., Donohoe, C., Akmaev, V. R., Sugarman, E. A., Labrousse, P., Boguslavskiy, L., Flynn, K., Rohlfs, E. M., Walker, A., Allitto, B., Sears, C., Scholl, T.
|
|
<strong>Differences in SMN1 allele frequencies among ethnic groups within North America. (Letter)</strong>
|
|
J. Med. Genet. 46: 641-644, 2009.
|
|
|
|
|
|
[PubMed: 19625283]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2009.066969]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heng, H. H. Q., Xie, B., Shi, X.-M., Tsui, L.-C., Mahuran, D. J.
|
|
<strong>Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus.</strong>
|
|
Genomics 18: 429-431, 1993.
|
|
|
|
|
|
[PubMed: 8288250]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1491]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hogenhuis, L. A. H., Spaulding, S. W., Engel, W. K.
|
|
<strong>Neuronal RNA metabolism in infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) studied by radioautography: a new technic in the investigation of neurological disease.</strong>
|
|
J. Neuropath. Exp. Neurol. 26: 335-341, 1967.
|
|
|
|
|
|
[PubMed: 6022173]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00005072-196704000-00010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hsieh-Li, H. M., Chang, J.-G., Jong, Y.-J., Wu, M.-H., Wang, N. M., Tsai, C. H., Li, H.
|
|
<strong>A mouse model for spinal muscular atrophy.</strong>
|
|
Nature Genet. 24: 66-70, 2000.
|
|
|
|
|
|
[PubMed: 10615130]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/71709]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jedrzejowska, M., Borkowska, J., Zimowski, J., Kostera-Pruszczyk, A., Milewski, M., Jurek, M., Sielska, D., Kostyk, E., Nyka, W., Zaremba, J., Hausmanowa-Petrusewicz, I.
|
|
<strong>Unaffected patients with a homozygous absence of the SMN1 gene.</strong>
|
|
Europ. J. Hum. Genet. 16: 930-934, 2008.
|
|
|
|
|
|
[PubMed: 18337729]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2008.41]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kariya, S., Park, G.-H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M. S., Landmesser, L. T., Monani, U. R.
|
|
<strong>Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 17: 2552-2569, 2008.
|
|
|
|
|
|
[PubMed: 18492800]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn156]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kaupmann, K., Simon-Chazottes, D., Guenet, J.-L., Jockusch, H.
|
|
<strong>Wobbler, a mutation affecting motoneuron survival and gonadal functions in the mouse, maps to proximal chromosome 11.</strong>
|
|
Genomics 13: 39-43, 1992.
|
|
|
|
|
|
[PubMed: 1349581]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90199-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kleyn, P. W., Brzustowicz, L. M., Wilhelmsen, K. C., Freimer, N. B., Miller, J. M., Munsat, T. L., Gilliam, T. C.
|
|
<strong>Spinal muscular atrophy is not the result of mutations at the beta-hexosaminidase or GM(2)-activator locus.</strong>
|
|
Neurology 41: 1418-1422, 1991.
|
|
|
|
|
|
[PubMed: 1679910]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.41.9.1418]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kye, M. J., Niederst, E. D., Wertz, M. H., Goncalves, I. C. G., Akten, B., Dover, K. Z., Peters, M., Riessland, M., Neveu, P., Wirth, B., Kosik, K. S., Sardi, S. P., Monani, U. R., Passini, M. A., Sahin, M.
|
|
<strong>SMN regulates axonal local translation via miR-183/mTOR pathway.</strong>
|
|
Hum. Molec. Genet. 23: 6318-6331, 2014.
|
|
|
|
|
|
[PubMed: 25055867]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu350]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S.
|
|
<strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong>
|
|
Genet. Med. 15: 178-186, 2013.
|
|
|
|
|
|
[PubMed: 22975760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/gim.2012.114]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lefebvre, S., Burglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., Le Paslier, D., Frezal, J., Cohen, D., Weissenbach, J., Munnich, A., Melki, J.
|
|
<strong>Identification and characterization of a spinal muscular atrophy-determining gene.</strong>
|
|
Cell 80: 155-165, 1995.
|
|
|
|
|
|
[PubMed: 7813012]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(95)90460-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lewin, B.
|
|
<strong>Genes for SMA: multum in parvo.</strong>
|
|
Cell 80: 1-5, 1995.
|
|
|
|
|
|
[PubMed: 7813005]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(95)90442-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lien, L. L., Boyce, F. M., Kleyn, P., Brzustowicz, L. M., Menninger, J., Ward, D. C., Gilliam, T. C., Kunkel, L. M.
|
|
<strong>Mapping of a gene encoding a dystrophin cross-reactive protein in close proximity to the spinal muscular atrophy locus. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49 (suppl.): 412, 1991.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lorson, C. L., Hahnen, E., Androphy, E. J., Wirth, B.
|
|
<strong>A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 6307-6311, 1999.
|
|
|
|
|
|
[PubMed: 10339583]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.11.6307]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lumaka, A., Bone, D., Lukoo, R., Mujinga, N., Senga, I., Tady, B., Matthijs, G., Lukusa, T. P.
|
|
<strong>Werdnig-Hoffmann disease: report of the first case clinically identified and genetically confirmed in Central Africa (Kinshasa-Congo).</strong>
|
|
Genet. Counsel. 20: 349-358, 2009.
|
|
|
|
|
|
[PubMed: 20162870]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lunn, M. R., Wang, C. H.
|
|
<strong>Spinal muscular atrophy.</strong>
|
|
Lancet 371: 2120-2133, 2008.
|
|
|
|
|
|
[PubMed: 18572081]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(08)60921-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marquardt, J. E., MacLowry, J., Perry, R. E.
|
|
<strong>Infantile progressive spinal muscular atrophy in identical Negro twins.</strong>
|
|
New Eng. J. Med. 267: 386-388, 1962.
|
|
|
|
|
|
[PubMed: 14470139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM196208232670804]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mattei, M.-G., Melki, J., Bachelot, M.-F., Abdelhak, S., Burlet, P., Frezal, J., Munnich, A.
|
|
<strong>In situ hybridization of two markers closely flanking the spinal muscular atrophy gene to 5q12-q13.3.</strong>
|
|
Cytogenet. Cell Genet. 57: 112-113, 1991.
|
|
|
|
|
|
[PubMed: 1914518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000133125]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthijs, G., Schollen, E., Legius, E., Devriendt, K., Goemans, N., Kayserili, H., Apak, M. Y., Cassiman, J.-J.
|
|
<strong>Unusual molecular findings in autosomal recessive spinal muscular atrophy.</strong>
|
|
J. Med. Genet. 33: 469-474, 1996.
|
|
|
|
|
|
[PubMed: 8782046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.33.6.469]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mattis, V. B., Ebert, A. D., Fosso, M. Y., Chang, C.-W., Lorson, C. L.
|
|
<strong>Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model.</strong>
|
|
Hum. Molec. Genet. 18: 3906-3913, 2009.
|
|
|
|
|
|
[PubMed: 19625298]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp333]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Medugorac, I., Kemter, J., Russ, I., Pietrowski, D., Nuske, S., Reichenbach, H.-D., Schmahl, W., Forster, M.
|
|
<strong>Mapping of the bovine spinal muscular atrophy locus to chromosome 24.</strong>
|
|
Mammalian Genome 14: 383-391, 2003.
|
|
|
|
|
|
[PubMed: 12879360]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00335-002-3024-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Melki, J., Abdelhak, S., Burlet, P., Raclin, V., Kaplan, J., Spiegel, R., Gilgenkrantz, S., Philip, N., Chauvet, M.-L., Dumez, Y., Briard, M.-L., Frezal, J., Munnich, A.
|
|
<strong>Prenatal prediction of Werdnig-Hoffmann disease using linked polymorphic DNA probes.</strong>
|
|
J. Med. Genet. 29: 171-174, 1992.
|
|
|
|
|
|
[PubMed: 1348092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.29.3.171]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Melki, J., Lefebvre, S., Burglen, L., Burlet, P., Clermont, O., Millasseau, P., Reboullet, S., Benichou, B., Zeviani, M., Le Paslier, D., Cohen, D., Weissenbach, J., Munnich, A.
|
|
<strong>De novo and inherited deletions of the 5q13 region in spinal muscular atrophies.</strong>
|
|
Science 264: 1474-1477, 1994.
|
|
|
|
|
|
[PubMed: 7910982]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7910982]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Melki, J., Sheth, P., Abdelhak, S., Burlet, P., Bachelot, M.-F., Lathrop, M. G., Frezal, J., Munnich, A., the French Spinal Muscular Atrophy Investigators.
|
|
<strong>Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14.</strong>
|
|
Lancet 336: 271-273, 1990.
|
|
|
|
|
|
[PubMed: 1973971]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0140-6736(90)91803-i]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer, K., Marquis, J., Trub, J., Nlend Nlend, R., Verp, S., Ruepp, M.-D., Imboden, H., Barde, I., Trono, D., Schumperli, D.
|
|
<strong>Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation.</strong>
|
|
Hum. Molec. Genet. 18: 546-555, 2009.
|
|
|
|
|
|
[PubMed: 19010792]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn382]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mostacciuolo, M. L., Danieli, G. A., Trevisan, C., Muller, E., Angelini, C.
|
|
<strong>Epidemiology of spinal muscular atrophies in a sample of the Italian population.</strong>
|
|
Neuroepidemiology 11: 34-38, 1992.
|
|
|
|
|
|
[PubMed: 1608493]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000110905]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muller, B., Melki, J., Burlet, P., Clerget-Darpoux, F.
|
|
<strong>Proximal spinal muscular atrophy (SMA) types II and III in the same sibship are not caused by different alleles at the SMA locus on 5q.</strong>
|
|
Am. J. Hum. Genet. 50: 892-895, 1992.
|
|
|
|
|
|
[PubMed: 1570842]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murray, L. M., Lee, S., Baumer, D., Parson, S. H., Talbot, K., Gillingwater, T. H.
|
|
<strong>Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 420-433, 2010.
|
|
|
|
|
|
[PubMed: 19884170]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp506]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Narver, H. L., Kong, L., Burnett, B. G., Choe, D. W., Bosch-Marce, M., Taye, A. A., Eckhaus, M. A., Sumner, C. J.
|
|
<strong>Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition.</strong>
|
|
Ann. Neurol. 64: 465-470, 2008.
|
|
|
|
|
|
[PubMed: 18661558]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21449]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Naryshkin, N. A., Weetall, M., Dakka, A., Narasimhan, J., Zhao, X., Feng, Z., Ling, K. K. Y., Karp, G. M., Qi, H., Woll, M. G., Chen, G., Zhang, N., and 36 others.
|
|
<strong>SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy.</strong>
|
|
Science 345: 688-693, 2014.
|
|
|
|
|
|
[PubMed: 25104390]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1250127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Novelli, G., Semprini, S., Capon, F., Dallapiccola, B.
|
|
<strong>A possible role of NAIP gene deletions in sex-related spinal muscular atrophy phenotype variation.</strong>
|
|
Neurogenetics 1: 29-30, 1997.
|
|
|
|
|
|
[PubMed: 10735271]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100480050004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ogino, S., Wilson, R. B.
|
|
<strong>Spinal muscular atrophy: molecular genetics and diagnosis.</strong>
|
|
Expert Rev. Molec. Diagn. 4: 15-29, 2004.
|
|
|
|
|
|
[PubMed: 14711346]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1586/14737159.4.1.15]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oprea, G. E., Kroeber, S., McWhorter, M. L., Rossoll, W., Mueller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., Wirth, B.
|
|
<strong>Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy.</strong>
|
|
Science 320: 524-527, 2008. Note: Erratum: Science 384: eadq4773, 2024.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oskoui, M., Levy, G., Garland, C. J., Gray, J. M., O'Hagen, J., De Vivo, D. C., Kaufmann, P.
|
|
<strong>The changing natural history of spinal muscular atrophy type 1.</strong>
|
|
Neurology 69: 1931-1936, 2007.
|
|
|
|
|
|
[PubMed: 17998484]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000290830.40544.b9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pascalet-Guidon, M.-J., Bois, E., Feingold, J., Mattei, J.-F., Combes, J.-C., Hamon, C.
|
|
<strong>Cluster of acute infantile spinal muscular atrophy (Werdnig-Hoffmann disease) in a limited area of Reunion Island.</strong>
|
|
Clin. Genet. 26: 39-42, 1984.
|
|
|
|
|
|
[PubMed: 6467653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1984.tb00785.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pearn, J. K., Carter, C. O., Wilson, J.
|
|
<strong>The genetic identity of acute infantile spinal muscular atrophy.</strong>
|
|
Brain 96: 463-470, 1973.
|
|
|
|
|
|
[PubMed: 4743929]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/96.3.463]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roy, N., Mahadevan, M. S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X., Salih, M., Aubry, H., Tamai, K., Guan, X., Ioannou, P., Crawford, T. O., de Jong, P. J., Surh, L., Ikeda, J.-E., Korneluk, R. G., MacKenzie, A.
|
|
<strong>The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.</strong>
|
|
Cell 80: 167-178, 1995.
|
|
|
|
|
|
[PubMed: 7813013]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(95)90461-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Berg, C., Zerres, K., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Heller, R.
|
|
<strong>Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling.</strong>
|
|
Clin. Genet. 76: 168-178, 2009.
|
|
|
|
|
|
[PubMed: 19780763]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01200.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudnik-Schoneborn, S., Heller, R., Berg, C., Betzler, C., Grimm, T., Eggermann, T., Eggermann, K., Wirth, R., Wirth, B., Zerres, K.
|
|
<strong>Congenital heart disease is a feature of severe infantile spinal muscular atrophy.</strong>
|
|
J. Med. Genet. 45: 635-638, 2008.
|
|
|
|
|
|
[PubMed: 18662980]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.057950]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Samilchuk, E., D'Souza, B., Bastaki, L.
|
|
<strong>Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy.</strong>
|
|
Hum. Genet. 98: 524-527, 1996.
|
|
|
|
|
|
[PubMed: 8882869]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050253]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scharf, J. M., Endrizzi, M. G., Wetter, A., Huang, S., Thompson, T. G., Zerres, K., Dietrich, W. F., Wirth, B., Kunkel, L. M.
|
|
<strong>Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics.</strong>
|
|
Nature Genet. 20: 83-86, 1998.
|
|
|
|
|
|
[PubMed: 9731538]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/1753]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sheng-Yuan, Z., Xiong, F., Chen, Y.-J., Yan, T.-Z., Zeng, J., Li, L., Zhang, Y.-N., Chen, W.-Q., Bao, X.-H., Zhang, C., Xu, X.-M.
|
|
<strong>Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.</strong>
|
|
Europ. J. Hum. Genet. 18: 978-984, 2010.
|
|
|
|
|
|
[PubMed: 20442745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2010.54]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Somerville, M. J., Hunter, A. G. W., Aubry, H. L., Korneluk, R. G., MacKenzie, A. E., Surh, L. C.
|
|
<strong>Clinical application of the molecular diagnosis of spinal muscular atrophy: deletions of neuronal apoptosis inhibitor protein and survival motor neuron genes.</strong>
|
|
Am. J. Med. Genet. 69: 159-165, 1997.
|
|
|
|
|
|
[PubMed: 9056553]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soubrouillard, C., Pellissier, J. F., Lepidi, H., Mancini, J., Rougon, G., Figarella-Branger, D.
|
|
<strong>Expression of developmentally regulated cytoskeleton and cell surface proteins in childhood spinal muscular atrophies.</strong>
|
|
J. Neurol. Sci. 133: 155-163, 1995.
|
|
|
|
|
|
[PubMed: 8583219]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-510x(95)00182-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spiegler, A. W. J., Hausmanowa-Petrusewicz, I., Borkowska, J., Klopocka, A.
|
|
<strong>Population data on acute infantile and chronic childhood spinal muscular atrophy in Warsaw.</strong>
|
|
Hum. Genet. 85: 211-214, 1990.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stratigopoulos, G., Lanzano, P., Deng, L., Guo, J., Kaufmann, P., Darras, B., Finkel, R., Tawil, R., McDermott, M. P., Martens, W., Devivo, D. C., Chung, W. K.
|
|
<strong>Association of plastin 3 expression with disease severity in spinal muscular atrophy only in postpubertal females.</strong>
|
|
Arch. Neurol. 67: 1252-1256, 2010.
|
|
|
|
|
|
[PubMed: 20937953]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneurol.2010.239]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, N. H., Dubowitz, V.
|
|
<strong>The natural history of type I (severe) spinal muscular atrophy.</strong>
|
|
Neuromusc. Disord. 4: 497-502, 1994.
|
|
|
|
|
|
[PubMed: 7881295]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0960-8966(94)90090-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, T. G., DiDonato, C. J., Simard, L. R., Ingraham, S. E., Burghes, A. H. M., Crawford, T. O., Rochette, C., Mendell, J. R., Wasmuth, J. J.
|
|
<strong>A novel cDNA detects homozygous microdeletions in greater than 50% of type I spinal muscular atrophy patients..</strong>
|
|
Nature Genet. 9: 56-62, 1995.
|
|
|
|
|
|
[PubMed: 7704025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0195-56]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ting, C.-H., Lin, C.-W., Wen, S.-L., Hsieh-Li, H.-M., Li, H.
|
|
<strong>Stat5 constitutive activation rescues defects in spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 16: 499-514, 2007.
|
|
|
|
|
|
[PubMed: 17220171]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddl482]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wen, H.-L., Lin, Y.-T., Ting, C.-H., Lin-Chao, S., Li, H., Hsieh-Li, H. M.
|
|
<strong>Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 1766-1778, 2010.
|
|
|
|
|
|
[PubMed: 20176735]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq058]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilmshurst, J. M., Reynolds, L., Van Toorn, R., Leisegang, F., Henderson, H. E.
|
|
<strong>Spinal muscular atrophy in black South Africans: concordance with the universal SMN1 genotype.</strong>
|
|
Clin. Genet. 62: 165-168, 2002.
|
|
|
|
|
|
[PubMed: 12220455]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620210.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilson, R. B., Ogino, S.
|
|
<strong>Carrier frequency of spinal muscular atrophy. (Letter)</strong>
|
|
Lancet 372: 1542 only, 2008.
|
|
|
|
|
|
[PubMed: 18984183]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(08)61645-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wirth, B., Rudnik-Schoneborn, S., Hahnen, E., Rohrig, D., Zerres, K.
|
|
<strong>Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2-q13.3): molecular genetics and clinical experience in 109 cases.</strong>
|
|
Prenatal Diag. 15: 407-417, 1995.
|
|
|
|
|
|
[PubMed: 7644431]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/pd.1970150503]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wirth, B., Schmidt, T., Hahnen, E., Rudnik-Schoneborn, S., Krawczak, M., Muller-Myhsok, B., Schonling, J., Zerres, K.
|
|
<strong>De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling.</strong>
|
|
Am. J. Hum. Genet. 61: 1102-1111, 1997.
|
|
|
|
|
|
[PubMed: 9345102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301608]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wirth, B., Voosen, B., Rohrig, D., Knapp, M., Piechaczek, B., Rudnik-Schoneborn, S., Zerres, K.
|
|
<strong>Fine mapping and narrowing of the genetic interval of the spinal muscular atrophy region by linkage studies.</strong>
|
|
Genomics 15: 113-118, 1993.
|
|
|
|
|
|
[PubMed: 8432521]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1018]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wirth, B.
|
|
<strong>An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA).</strong>
|
|
Hum. Mutat. 15: 228-237, 2000.
|
|
|
|
|
|
[PubMed: 10679938]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wishart, T. M., Huang, J. P.-W., Murray, L. M., Lamont, D. J., Mutsaers, C. A., Ross, J., Geldsetzer, P., Ansorge, O., Talbot, K., Parson, S. H., Gillingwater, T. H.
|
|
<strong>SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy.</strong>
|
|
Hum. Molec. Genet. 19: 4216-4228, 2010.
|
|
|
|
|
|
[PubMed: 20705736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq340]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Workman, E., Saieva, L., Carrel, T. L., Crawford, T. O., Liu, D., Lutz, C., Beattie, C. E., Pellizzoni, L., Burghes, A. H. M.
|
|
<strong>A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice.</strong>
|
|
Hum. Molec. Genet. 18: 2215-2229, 2009.
|
|
|
|
|
|
[PubMed: 19329542]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp157]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yuo, C.-Y., Lin, H.-H., Chang, Y.-S., Yang, W.-K., Chang, J.-G.
|
|
<strong>5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells.</strong>
|
|
Ann. Neurol. 63: 26-34, 2008.
|
|
|
|
|
|
[PubMed: 17924536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21241]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zaldivar, T., Montejo, Y., Acevedo, A. M., Guerra, R., Vargas, J., Garofalo, N., Alvarez, R., Alvarez, M. A., Hardiman, O.
|
|
<strong>Evidence of reduced frequency of spinal muscular atrophy type I in the Cuban population.</strong>
|
|
Neurology 65: 636-638, 2005.
|
|
|
|
|
|
[PubMed: 16116135]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000172860.41953.12]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zerres, K., Grimm, T.
|
|
<strong>Genetic counseling in families with spinal muscular atrophy type Kugelberg-Welander.</strong>
|
|
Hum. Genet. 65: 74-75, 1983.
|
|
|
|
|
|
[PubMed: 6642509]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00285033]
|
|
|
|
|
|
</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">
|
|
George E. Tiller - updated : 06/23/2017<br>Patricia A. Hartz - updated : 01/20/2015<br>Ada Hamosh - updated : 8/29/2014<br>Patricia A. Hartz - updated : 9/4/2013<br>Anne M. Stumpf - updated : 4/18/2013<br>Cassandra L. Kniffin - updated : 3/21/2012<br>Cassandra L. Kniffin - updated : 1/10/2012<br>George E. Tiller - updated : 12/1/2011<br>George E. Tiller - updated : 11/21/2011<br>Cassandra L. Kniffin - updated : 10/10/2011<br>Cassandra L. Kniffin - updated : 7/21/2011<br>George E. Tiller - updated : 1/5/2011<br>George E. Tiller - updated : 8/10/2010<br>Cassandra L. Kniffin - updated : 6/8/2010<br>Cassandra L. Kniffin - updated : 3/15/2010<br>George E. Tiller - updated : 3/3/2010<br>Cassandra L. Kniffin - updated : 12/30/2009<br>Cassandra L. Kniffin - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 11/2/2009<br>Cassandra L. Kniffin - updated : 8/28/2009<br>George E. Tiller - updated : 8/14/2009<br>Cassandra L. Kniffin - updated : 7/14/2009<br>Cassandra L. Kniffin - updated : 2/25/2009<br>Ada Hamosh - updated : 2/24/2009<br>Cassandra L. Kniffin - updated : 2/12/2009<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Ada Hamosh - updated : 6/17/2008<br>Cassandra L. Kniffin - updated : 5/12/2008<br>Cassandra L. Kniffin - updated : 3/6/2008<br>Cassandra L. Kniffin - updated : 8/6/2007<br>Cassandra L. Kniffin - updated : 12/5/2005<br>Cassandra L. Kniffin - reorganized : 11/21/2005<br>Cassandra L. Kniffin - updated : 11/2/2005<br>George E. Tiller - updated : 9/12/2005<br>George E. Tiller - updated : 3/17/2005<br>George E. Tiller - updated : 3/17/2005<br>Cassandra L. Kniffin - updated : 5/7/2004<br>Victor A. McKusick - updated : 12/9/2003<br>Victor A. McKusick - updated : 11/25/2002<br>Victor A. McKusick - updated : 10/15/2001<br>George E. Tiller - updated : 1/16/2001<br>George E. Tiller - updated : 12/4/2000<br>Victor A. McKusick - updated : 3/15/1999<br>Michael J. Wright - updated : 2/11/1999<br>Victor A. McKusick - updated : 8/28/1998<br>Victor A. McKusick - updated : 11/26/1997<br>Victor A. McKusick - updated : 9/5/1997<br>Victor A. McKusick - updated : 8/20/1997<br>Victor A. McKusick - updated : 5/15/1997<br>Victor A. McKusick - updated : 4/15/1997<br>Moyra Smith - updated : 1/14/1997<br>Moyra Smith - updated : 12/31/1996<br>Iosif W. Lurie - updated : 7/10/1996<br>Moyra Smith - updated : 4/23/1996<br>Orest Hurko - updated : 3/6/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</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 : 07/19/2024<br>carol : 01/20/2022<br>carol : 04/02/2021<br>mgross : 02/15/2018<br>alopez : 06/23/2017<br>carol : 05/01/2017<br>carol : 03/25/2017<br>alopez : 09/16/2016<br>mgross : 01/20/2015<br>alopez : 8/29/2014<br>mgross : 9/4/2013<br>alopez : 5/30/2013<br>alopez : 4/18/2013<br>mgross : 5/11/2012<br>carol : 3/21/2012<br>carol : 3/21/2012<br>ckniffin : 1/10/2012<br>alopez : 12/5/2011<br>terry : 12/1/2011<br>carol : 11/22/2011<br>carol : 11/21/2011<br>terry : 11/21/2011<br>carol : 10/12/2011<br>ckniffin : 10/10/2011<br>wwang : 7/26/2011<br>ckniffin : 7/21/2011<br>wwang : 1/14/2011<br>terry : 1/5/2011<br>wwang : 8/10/2010<br>carol : 7/30/2010<br>wwang : 6/15/2010<br>ckniffin : 6/8/2010<br>terry : 5/11/2010<br>wwang : 3/19/2010<br>ckniffin : 3/15/2010<br>wwang : 3/15/2010<br>terry : 3/3/2010<br>wwang : 1/21/2010<br>carol : 1/8/2010<br>ckniffin : 12/30/2009<br>wwang : 12/1/2009<br>wwang : 11/24/2009<br>ckniffin : 11/10/2009<br>carol : 11/4/2009<br>ckniffin : 11/2/2009<br>wwang : 10/30/2009<br>ckniffin : 8/28/2009<br>wwang : 8/14/2009<br>wwang : 7/30/2009<br>ckniffin : 7/14/2009<br>carol : 3/5/2009<br>ckniffin : 2/25/2009<br>alopez : 2/24/2009<br>wwang : 2/20/2009<br>ckniffin : 2/12/2009<br>wwang : 8/28/2008<br>terry : 8/26/2008<br>ckniffin : 8/19/2008<br>alopez : 6/20/2008<br>alopez : 6/20/2008<br>terry : 6/17/2008<br>wwang : 5/19/2008<br>ckniffin : 5/12/2008<br>wwang : 5/8/2008<br>ckniffin : 3/6/2008<br>wwang : 8/21/2007<br>ckniffin : 8/6/2007<br>carol : 2/1/2006<br>wwang : 12/5/2005<br>carol : 11/22/2005<br>carol : 11/21/2005<br>ckniffin : 11/2/2005<br>alopez : 10/20/2005<br>terry : 9/12/2005<br>alopez : 3/17/2005<br>alopez : 3/17/2005<br>tkritzer : 5/10/2004<br>ckniffin : 5/7/2004<br>tkritzer : 12/17/2003<br>terry : 12/9/2003<br>carol : 11/14/2003<br>cwells : 11/25/2002<br>terry : 11/20/2002<br>ckniffin : 5/7/2002<br>cwells : 3/13/2002<br>mcapotos : 10/15/2001<br>mcapotos : 1/26/2001<br>mcapotos : 1/19/2001<br>mcapotos : 1/16/2001<br>terry : 12/4/2000<br>carol : 8/26/1999<br>terry : 7/7/1999<br>carol : 3/15/1999<br>terry : 3/15/1999<br>carol : 2/17/1999<br>terry : 2/11/1999<br>dkim : 12/10/1998<br>carol : 11/16/1998<br>alopez : 8/31/1998<br>terry : 8/28/1998<br>terry : 12/3/1997<br>terry : 11/26/1997<br>terry : 9/12/1997<br>terry : 9/5/1997<br>jenny : 8/22/1997<br>terry : 8/20/1997<br>jenny : 5/15/1997<br>terry : 5/12/1997<br>jenny : 4/15/1997<br>terry : 4/8/1997<br>terry : 1/14/1997<br>mark : 1/14/1997<br>mark : 12/31/1996<br>joanna : 12/2/1996<br>carol : 7/10/1996<br>carol : 4/26/1996<br>carol : 4/23/1996<br>terry : 4/15/1996<br>mark : 3/6/1996<br>terry : 2/29/1996<br>mimman : 2/8/1996<br>mark : 9/12/1995<br>terry : 2/27/1995<br>carol : 2/17/1995<br>jason : 6/15/1994<br>mimadm : 5/4/1994<br>warfield : 3/30/1994
|
|
</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>
|
|
|
|
|