4341 lines
353 KiB
Text
4341 lines
353 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
|
|
|
|
- *602783 - SPG7 MATRIX AAA PEPTIDASE SUBUNIT, PARAPLEGIN; SPG7
|
|
|
|
|
|
- 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=602783"><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">*602783</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/602783">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000197912;t=ENST00000645818" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=6687" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=602783" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000197912;t=ENST00000645818" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001363850,NM_003119,NM_199367,XM_005256321,XM_017023598,XM_047434537,XM_047434538,XM_047434539,XM_047434540" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_003119" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=602783" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=04149&isoform_id=04149_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/SPG7" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/219526,265103,452753,2853614,3273089,4507173,4704460,6690198,40806173,62020635,116242796,119587130,119587131,119587132,119587133,193787692,530424748,1034595762,1394533423,2217307198,2217307200,2217307202,2217307205,2462550477,2462550479,2462550481,2462550483,2462550485" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/Q9UQ90" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=6687" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000197912;t=ENST00000645818" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=SPG7" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=SPG7" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+6687" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/SPG7" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:6687" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/6687" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr16&hgg_gene=ENST00000645818.2&hgg_start=89508388&hgg_end=89557768&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:11237" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/spg7" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602783[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602783[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/SPG7/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000197912" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=SPG7" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=SPG7" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SPG7" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SPG7&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA36067" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:11237" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0024992.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:2385906" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/SPG7#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:2385906" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/6687/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=6687" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
|
|
<div id="mimWormbaseGeneFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021425;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021425 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021615;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021615 </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030131-5391" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=SPG7&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
602783
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SPG7 MATRIX AAA PEPTIDASE SUBUNIT, PARAPLEGIN; SPG7
|
|
|
|
</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">
|
|
SPG7 GENE<br />
|
|
PARAPLEGIN; PGN<br />
|
|
CELL MATRIX ADHESION REGULATOR; CMAR<br />
|
|
CELL ADHESION REGULATOR; CAR
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SPG7" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SPG7</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/16/745?start=-3&limit=10&highlight=745">16q24.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:89508388-89557768&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">16:89,508,388-89,557,768</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/16/745?start=-3&limit=10&highlight=745">
|
|
16q24.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Spastic paraplegia 7, autosomal recessive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/607259"> 607259 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/602783" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/602783" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The SPG7 gene encodes paraplegin, a component of the m-AAA protease. The m-AAA protease is an ATP-dependent proteolytic complex of the mitochondrial inner membrane that degrades misfolded proteins and regulates ribosome assembly (<a href="#10" class="mim-tip-reference" title="Koppen, M., Metodiev, M. D., Casari, G., Rugarli, E. I., Langer, T. <strong>Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia.</strong> Molec. Cell. Biol. 27: 758-767, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17101804[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/10.1128/MCB.01470-06" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17101804">Koppen et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17101804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Based on linkage analysis of a family with autosomal recessive spastic paraplegia that mapped to 16q24.3 (SPG7; <a href="/entry/607259">607259</a>), <a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> used an EST clone to screen a human cDNA library and isolate a candidate gene. The full-length cDNA sequence corresponding to this gene encoded a deduced 795-amino acid protein, which they named paraplegin. Northern blot analysis detected a transcript of approximately 3.2 kb in all fetal and adult tissues tested. Two additional hybridizing transcripts of approximately 2.6 and 7.5 kb were detected in heart and pancreas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9635427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> concluded that the CAR gene identified by <a href="#15" class="mim-tip-reference" title="Pullman, W. E., Bodmer, W. F. <strong>Cloning and characterization of a gene that regulates cell adhesion.</strong> Nature 356: 529-532, 1992. Note: Erratum: Nature 361: 564 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1560826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1560826</a>] [<a href="https://doi.org/10.1038/356529a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1560826">Pullman and Bodmer (1992)</a> as a 459-bp transcript colinear with genomic DNA is part of the 3-prime untranscribed region of the SPG7 gene. Among other evidence supporting their conclusion, <a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> found a sequence 100% identical to the CAR sequence in over 30 different SPG7 clones, including ESTs, identified from many different cDNA libraries. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1560826+9635427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Settasatian, C., Whitmore, S. A., Crawford, J., Bilton, R. L., Cleton-Jansen, A.-M., Sutherland, G. R., Callen, D. F. <strong>Genomic structure and expression analysis of the spastic paraplegia gene, SPG7.</strong> Hum. Genet. 105: 139-144, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480368</a>] [<a href="https://doi.org/10.1007/s004399900087" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10480368">Settasatian et al. (1999)</a> determined that the SPG7 gene contains 17 exons, ranging from 78 to 242 bp, and spans approximately 52 kb. The exon/intron boundaries and all splice junctions are consistent with consensus sequences for donor and acceptor sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480368" 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 genetic linkage analysis using a TaqI polymorphism in CEPH families, <a href="#11" class="mim-tip-reference" title="Koyama, K., Emi, M., Nakamura, Y. <strong>The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis.</strong> Genomics 16: 264-265, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8098008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8098008</a>] [<a href="https://doi.org/10.1006/geno.1993.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8098008">Koyama et al. (1993)</a> demonstrated that CAR is close to D16S7 and D16S154, which are located in the 'peritelomeric' region of 16q. <a href="#12" class="mim-tip-reference" title="Mangion, J., Rahman, N., Mansour, S., Brice, G., Rosbotham, J., Child, A. H., Murday, V. A., Mortimer, P. S., Barfoot, R., Sigurdsson, A., Edkins, S., Sarfarazi, M., Burnand, K., Evans, A. L., Nunan, T. O., Stratton, M. R., Jeffery, S. <strong>A gene for lymphedema-distichiasis maps to 16q24.3.</strong> Am. J. Hum. Genet. 65: 427-432, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417285</a>] [<a href="https://doi.org/10.1086/302500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417285">Mangion et al. (1999)</a> stated that the CMAR gene maps to 16q24.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10417285+8098008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By positional cloning, <a href="#5" class="mim-tip-reference" title="De Michele, G., De Fusco, M., Cavalcanti, F., Filla, A., Marconi, R., Volpe, G., Monticelli, A., Ballabio, A., Casari, G., Cocozza, S. <strong>A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.</strong> Am. J. Hum. Genet. 63: 135-139, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634528</a>] [<a href="https://doi.org/10.1086/301930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634528">De Michele et al. (1998)</a> identified the SPG7 gene within the 16q24.3 critical region for autosomal recessive spastic paraplegia-7 (<a href="/entry/607259">607259</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#15" class="mim-tip-reference" title="Pullman, W. E., Bodmer, W. F. <strong>Cloning and characterization of a gene that regulates cell adhesion.</strong> Nature 356: 529-532, 1992. Note: Erratum: Nature 361: 564 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1560826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1560826</a>] [<a href="https://doi.org/10.1038/356529a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1560826">Pullman and Bodmer (1992)</a> suggested that the CAR gene encodes an adhesion signal transduction molecule that functions in the suppression of tumor invasion. <a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> presented data calling this functional information into question. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1560826+9635427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> determined that paraplegin is highly homologous to the yeast mitochondrial ATPases AFG3, RCA1, and YME1 (see <a href="/entry/607472">607472</a>), which have both proteolytic and chaperone-like activities at the inner mitochondrial membrane. Immunofluorescence analysis and import experiments showed that paraplegin localizes to mitochondria. Analysis of muscle biopsies from 2 patients with paraplegin mutations showed typical signs of mitochondrial OXPHOS defects, thus suggesting a mechanism for neurodegeneration in SPG-type disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9635427" 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>Consistent with a role for paraplegin in mitochondrial function, muscle biopsies obtained from some patients with SPG7 mutations showed typical signs of mitochondrial disease (<a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al., 1998</a>). These included ragged-red fibers, intense succinate dehydrogenase-stained areas, and cytochrome oxidase-negative fibers. Furthermore, the degree of mitochondrial abnormality correlated with the severity of the disease. Taken together, these findings suggested that a mitochondrial-based mechanism underlies spastic paraplegia-7. <a href="#4" class="mim-tip-reference" title="Crosby, A. H., Proukakis, C. <strong>Is the transportation highway the right road for hereditary spastic paraplegia? (Editorial)</strong> Am. J. Hum. Genet. 71: 1009-1016, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355399</a>] [<a href="https://doi.org/10.1086/344206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355399">Crosby and Proukakis (2002)</a> cited preliminary reports of electron microscopy studies in mice lacking paraplegin that revealed that, long before degeneration, the axons were filled with abnormal mitochondria. Subsequently, swollen axons containing accumulated organelles and neurofilaments were seen, which suggested that mitochondrial dysfunction may lead to axonal degeneration by impairing axonal transport. <a href="#4" class="mim-tip-reference" title="Crosby, A. H., Proukakis, C. <strong>Is the transportation highway the right road for hereditary spastic paraplegia? (Editorial)</strong> Am. J. Hum. Genet. 71: 1009-1016, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355399</a>] [<a href="https://doi.org/10.1086/344206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355399">Crosby and Proukakis (2002)</a> concluded that aberrant cellular trafficking dynamics appears to be a common process responsible for the pattern of neurodegeneration seen in hereditary spastic paraplegia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9635427+12355399" 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 in vitro protein binding assays and immunoprecipitation analysis, <a href="#10" class="mim-tip-reference" title="Koppen, M., Metodiev, M. D., Casari, G., Rugarli, E. I., Langer, T. <strong>Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia.</strong> Molec. Cell. Biol. 27: 758-767, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17101804[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/10.1128/MCB.01470-06" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17101804">Koppen et al. (2007)</a> showed that paraplegin interacted with AFG3L2 (<a href="/entry/604581">604581</a>) in the m-AAA protease complex. Paraplegin did not interact with itself. Loss of paraplegin in Spg7 -/- mice or in SPG7 patient fibroblasts resulted in m-AAA protease complexes made up of only homodimerized AFG3L2 that were proteolytically active in yeast complementation assays. <a href="#2" class="mim-tip-reference" title="Bonn, F., Pantakani, K., Shoukier, M., Langer, T., Mannan, A. U. <strong>Functional evaluation of paraplegin mutations by a yeast complementation assay.</strong> Hum. Mutat. 31: 617-621, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186691</a>] [<a href="https://doi.org/10.1002/humu.21226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20186691">Bonn et al. (2010)</a> used the yeast complementation assay to evaluate the functional consequences of pathogenic mutations (see, e.g., <a href="#0010">602783.0010</a> and <a href="#0011">602783.0011</a>) in the SPG7 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20186691+17101804" 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="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> found that all affected individuals from the SPG7 family reported by <a href="#5" class="mim-tip-reference" title="De Michele, G., De Fusco, M., Cavalcanti, F., Filla, A., Marconi, R., Volpe, G., Monticelli, A., Ballabio, A., Casari, G., Cocozza, S. <strong>A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.</strong> Am. J. Hum. Genet. 63: 135-139, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634528</a>] [<a href="https://doi.org/10.1086/301930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634528">De Michele et al. (1998)</a> were homozygous for a 9.5-kb deletion (<a href="#0003">602783.0003</a>) in the SPG7 gene. In 2 additional unrelated families with autosomal recessive SPG, 1 demonstrating a pure form of the disorder and 1 demonstrating a complicated form of the disorder, <a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> identified 2 additional homozygous paraplegin mutations (<a href="#0001">602783.0001</a>-<a href="#0002">602783.0002</a>), both resulting in a frameshift and a truncated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9635427+9634528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Koyama, K., Emi, M., Nakamura, Y. <strong>The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis.</strong> Genomics 16: 264-265, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8098008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8098008</a>] [<a href="https://doi.org/10.1006/geno.1993.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8098008">Koyama et al. (1993)</a> identified an insertion/deletion polymorphism in the coding region of the CMAR gene; the variant was detected in 9 chromosomes among 30 unrelated Japanese individuals. <a href="#6" class="mim-tip-reference" title="Durbin, H., Novelli, M., Bodmer, W. <strong>Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR).</strong> Genomics 19: 181-182, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7993411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7993411</a>] [<a href="https://doi.org/10.1006/geno.1994.1038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7993411">Durbin et al. (1994)</a> detected a 4-bp insertion (CACA) at nucleotide 241 of the CMAR gene. <a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> noted that the polymorphisms identified by <a href="#11" class="mim-tip-reference" title="Koyama, K., Emi, M., Nakamura, Y. <strong>The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis.</strong> Genomics 16: 264-265, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8098008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8098008</a>] [<a href="https://doi.org/10.1006/geno.1993.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8098008">Koyama et al. (1993)</a> and <a href="#6" class="mim-tip-reference" title="Durbin, H., Novelli, M., Bodmer, W. <strong>Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR).</strong> Genomics 19: 181-182, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7993411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7993411</a>] [<a href="https://doi.org/10.1006/geno.1994.1038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7993411">Durbin et al. (1994)</a> would result in major changes in the CMAR putative protein product, suggesting that the original CMAR cDNA clone may not encode a protein in vivo and that functional data obtained using CMAR cDNA in transfection experiments may be due to artifactual translation of a peptide encoded by the CMAR sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9635427+7993411+8098008" 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 1 (0.7%) of 136 index patients with autosomal recessive SPG, <a href="#7" class="mim-tip-reference" title="Elleuch, N., Depienne, C., Benomar, A., Ouvrard Hernandez, A. M., Ferrer, X., Fontaine, B., Grid, D., Tallaksen, C. M. E., Zemmouri, R., Stevanin, G., Durr, A., Brice, A. <strong>Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia.</strong> Neurology 66: 654-659, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16534102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16534102</a>] [<a href="https://doi.org/10.1212/01.wnl.0000201185.91110.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16534102">Elleuch et al. (2006)</a> identified 2 mutations in the SPG7 gene (<a href="#0004">602783.0004</a>-<a href="#0005">602783.0005</a>). Twenty families had at least 1 variant in the SPG7 gene that was not found in 550 control chromosomes. In 4 of these families, mutations were predicted to be highly deleterious, suggesting that they may have contributed to the phenotype. The authors identified several additional rare variants in the SPG7 gene, which were of undetermined significance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16534102" 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="Arnoldi, A., Tonelli, A., Crippa, F., Villani, G., Pacelli, C., Sironi, M., Pozzoli, U., D'Angelo, M. G., Meola, G., Martinuzzi, A., Crimella, C., Redaelli, F., Panzeri, C., Renieri, A., Comi, G. P., Turconi, A. C., Bresolin, N., Bassi, M. T. <strong>A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.</strong> Hum. Mutat. 29: 522-531, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18200586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18200586</a>] [<a href="https://doi.org/10.1002/humu.20682" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18200586">Arnoldi et al. (2008)</a> identified 7 different SPG7 mutations (see, e.g., <a href="#0007">602783.0007</a>-<a href="#0009">602783.0009</a>) in 6 (4.4%) of 135 Italian patients with spastic paraplegia. Four of the patients were heterozygous for the mutations, which fell within conserved domains of the protein and were not found in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18200586" 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="#16" class="mim-tip-reference" title="Sanchez-Ferrero, E., Coto, E., Beetz, C., Gamez, J., Corao, A. I., Diaz, M., Esteban, J., del Castillo, E., Moris, G., Infante, J., Menendez, M., Pascual-Pascual, S. I., Lopez de Munain, A., Garcia-Barcina, M. J., Alvarez, V. <strong>SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.</strong> Clin. Genet. 83: 257-262, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22571692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22571692</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01896.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22571692">Sanchez-Ferrero et al. (2013)</a> sequenced the SPG7 gene in 285 Spanish patients with spastic paraplegia who were negative for mutations in the SPG4 (<a href="/entry/604277">604277</a>) and SPG3A (<a href="/entry/606439">606439</a>) genes. Fourteen SPG7 mutations, including 12 novel mutations, were identified in 14 patients. The mutations included 2 large deletions, 5 missense changes, 4 nonsense mutations, 2 frameshift insertion/deletions, and 1 splice site mutation. Thirteen patients had only a single heterozygous mutation, suggesting a dominant effect for some SPG7 mutations. Functional studies were not performed to assess the biologic significance. An A510V substitution (<a href="#0012">602783.0012</a>) was found in 8 patients (3%): 4 carried A510V in compound heterozygous state with another SPG7 mutation, 1 was homozygous for A510V, and 3 patients were heterozygous for A510V. The A510V substitution was also identified in 1% of controls. All patients had adult onset of the disorder, but only 35% had a complicated phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22571692" 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 57-year-old man, born to first-cousin Caucasian parents, with childhood optic nerve atrophy and SPG7, <a href="#8" class="mim-tip-reference" title="Eriksen, K. O., Wigers, A. R., Wedding, I. M., Erichsen, A. K., Baroy, T., Soberg, K., Jorstad, O. K. <strong>A novel homozygous variant in the SPG7 gene presenting with childhood optic nerve atrophy.</strong> Am. J. Ophthal. Case Rep. 26: 101400, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35243150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35243150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35243150[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajoc.2022.101400" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35243150">Eriksen et al. (2022)</a> identified a homozygous mutation in the SPG7 gene (M1?; <a href="#0013">602783.0013</a>), which alters the start codon and is expected to abolish production of paraplegin. The patient had onset of vision loss at age 6 years, but findings of spastic paraplegia were subtle and the diagnosis was not suspected until the likely pathogenic variant in the SPG7 gene was identified. The authors noted that the SPG7 gene should be added to the workup of suspected hereditary optic neuropathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35243150" 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>Exclusion Studies</em></strong></p><p>
|
|
Because the SPG7 gene was mapped to chromosome 16q24.3, a region of frequent loss of heterozygosity (LOH) in sporadic breast and prostate cancer, <a href="#17" class="mim-tip-reference" title="Settasatian, C., Whitmore, S. A., Crawford, J., Bilton, R. L., Cleton-Jansen, A.-M., Sutherland, G. R., Callen, D. F. <strong>Genomic structure and expression analysis of the spastic paraplegia gene, SPG7.</strong> Hum. Genet. 105: 139-144, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480368</a>] [<a href="https://doi.org/10.1007/s004399900087" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10480368">Settasatian et al. (1999)</a> performed SSCP analysis of 10 exons of this gene in a number of sporadic breast cancer samples showing LOH at 16q24.3. No mutations were detected; only SNPs were observed in 1 exon and 3 introns. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480368" 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><a href="#9" class="mim-tip-reference" title="Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L., Casari, G., Ballabio, A., Rugarli, E. I. <strong>Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport.</strong> J. Clin. Invest. 113: 231-242, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722615[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/10.1172/JCI20138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722615">Ferreirinha et al. (2004)</a> developed a mouse model for autosomal recessive hereditary spastic paraplegia due to mutation in the SPG7 gene, which encodes the mitochondrial ATPase paraplegin. Paraplegin-deficient mice were affected by a distal axonopathy of spinal and peripheral axons, characterized by axonal swelling and degeneration. <a href="#9" class="mim-tip-reference" title="Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L., Casari, G., Ballabio, A., Rugarli, E. I. <strong>Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport.</strong> J. Clin. Invest. 113: 231-242, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722615[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/10.1172/JCI20138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722615">Ferreirinha et al. (2004)</a> found that mitochondrial morphologic abnormalities occurred in synaptic terminals and in distal regions of axons long before the first signs of swelling and degeneration and correlated with onset of motor impairment. Axonal swellings occurred through massive accumulation of organelles and neurofilaments, suggesting impairment of anterograde axonal transport. Retrograde axonal transport was delayed in symptomatic mice. <a href="#9" class="mim-tip-reference" title="Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L., Casari, G., Ballabio, A., Rugarli, E. I. <strong>Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport.</strong> J. Clin. Invest. 113: 231-242, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722615[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/10.1172/JCI20138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722615">Ferreirinha et al. (2004)</a> speculated that local failure of mitochondrial function may affect axonal transport and cause axonal degeneration. They concluded that a timely therapeutic intervention might prevent the loss of axons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722615" 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 Spg7-null mice, <a href="#14" class="mim-tip-reference" title="Pirozzi, M., Quattrini, A., Andolfi, G., Dina, G., Malaguti, M. C., Auricchio, A., Rugarli, E. I. <strong>Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia.</strong> J. Clin. Invest. 116: 202-208, 2006. Note: Erratum: J. Clin. Invest. 124: 871 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357941</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16357941[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/10.1172/JCI26210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16357941">Pirozzi et al. (2006)</a> found that intramuscular delivery of adeno-associated virus vector containing Spg7 halted the progression of neuropathologic changes and rescued disease-associated morphologic changes in the mitochondria of peripheral nerves. A single injection before onset of symptoms improved motor performance of mice for up to 10 months, suggesting that peripheral neuropathy contributes to the clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16357941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Martinelli, P., La Mattina, V., Bernacchia, A., Magnoni, R., Cerri, F., Cox, G., Quattrini, A., Casari, G., Rugarli, E. I. <strong>Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration.</strong> Hum. Molec. Genet. 18: 2001-2013, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19289403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19289403</a>] [<a href="https://doi.org/10.1093/hmg/ddp124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19289403">Martinelli et al. (2009)</a> reported an early-onset severe neurologic phenotype in Spg7-null/Afg3l2 +/- double-mutant mice characterized by loss of balance, tremor, and ataxia. Double-mutant mice displayed acceleration and worsening of the axonopathy observed in Spg7-null mice. In addition, they showed prominent cerebellar degeneration with loss of Purkinje cells and parallel fibers, and reactive astrogliosis. Mitochondria from affected tissues were prone to lose mtDNA and had unstable respiratory complexes. At late stages, neurons contained structural abnormal mitochondria defective in COX-SDH reaction. <a href="#13" class="mim-tip-reference" title="Martinelli, P., La Mattina, V., Bernacchia, A., Magnoni, R., Cerri, F., Cox, G., Quattrini, A., Casari, G., Rugarli, E. I. <strong>Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration.</strong> Hum. Molec. Genet. 18: 2001-2013, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19289403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19289403</a>] [<a href="https://doi.org/10.1093/hmg/ddp124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19289403">Martinelli et al. (2009)</a> suggested that different neuronal populations may have variable thresholds of susceptibility to reduced levels of the m-AAA protease, and that impaired mitochondrial proteolysis may be a mechanism of cerebellar degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19289403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>13 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/602783" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602783[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 2-BP DEL, NT784
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs768136171 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs768136171;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs768136171?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs768136171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs768136171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000615294 OR RCV000989664 OR RCV003403411 OR RCV005000374" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000615294, RCV000989664, RCV003403411, RCV005000374" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000615294...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 2 brothers from a small village in southern Italy who had autosomal recessive hereditary pure spastic paraplegia (SPG7; <a href="/entry/607259">607259</a>), <a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> identified a 2-bp deletion (784del2) in the SPG7 gene. This mutation causes a frameshift that abolishes approximately 60% of the protein. The patient, who showed typical signs of pure SPG with an age of onset of 26 years, was homozygous for this mutation; consanguinity was very likely. The other brother was unavailable for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9635427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 1-BP INS, 2228A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs763126378 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763126378;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs763126378?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs763126378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs763126378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001091058 OR RCV001760064" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001091058, RCV001760064" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001091058...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> found a mutation in the SPG7 gene in a French family in which complicated SPG segregated as an autosomal recessive trait (SPG7; <a href="/entry/607259">607259</a>). Patients from this family were affected by a form of SPG with a mean age of onset of 34 years. They showed progressive weakness and spasticity of the lower limbs, decreased perception of sharp stimulation, diminished vibratory sense, and urinary incontinence, which are typical signs of SPG. These patients also had optic atrophy (3 of 3 examined), cortical atrophy (1 of 3 examined), and cerebellar atrophy (2 of 3 examined). All affected sibs from this family were homozygous for an A insertion at position 2228 of the paraplegin cDNA, while their mother was heterozygous for the same mutation. This insertion creates a frameshift and a stop codon only 2 amino acids downstream, resulting in a truncated form of paraplegin that is missing 57 amino acids at the C terminus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9635427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 9.5-KB DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007214" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007214" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007214</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A. <strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong> Cell 93: 973-983, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9635427">Casari et al. (1998)</a> found that all affected individuals from the family with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>) reported by <a href="#5" class="mim-tip-reference" title="De Michele, G., De Fusco, M., Cavalcanti, F., Filla, A., Marconi, R., Volpe, G., Monticelli, A., Ballabio, A., Casari, G., Cocozza, S. <strong>A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.</strong> Am. J. Hum. Genet. 63: 135-139, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634528</a>] [<a href="https://doi.org/10.1086/301930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634528">De Michele et al. (1998)</a> were homozygous for a 9.5-kb deletion in the SPG7 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9635427+9634528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 2-BP DEL, 1-BP INS, 850
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs768595656 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs768595656;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs768595656?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs768595656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs768595656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000640978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000640978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000640978</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected sibs of a Moroccan family with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#7" class="mim-tip-reference" title="Elleuch, N., Depienne, C., Benomar, A., Ouvrard Hernandez, A. M., Ferrer, X., Fontaine, B., Grid, D., Tallaksen, C. M. E., Zemmouri, R., Stevanin, G., Durr, A., Brice, A. <strong>Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia.</strong> Neurology 66: 654-659, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16534102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16534102</a>] [<a href="https://doi.org/10.1212/01.wnl.0000201185.91110.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16534102">Elleuch et al. (2006)</a> identified compound heterozygosity for 2 mutations in the SPG7 gene. One allele had a 2-bp deletion and 1-bp insertion (850delTTinsC), resulting in premature termination of the protein. The second allele had an in-frame deletion (1742delTGG; <a href="#0005">602783.0005</a>), resulting in the deletion of val581. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16534102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 3-BP DEL, 1742TGG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1597661607 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1597661607;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1597661607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1597661607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007216" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007216" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007216</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the in-frame deletion in the SPG7 gene (1742delTGG) that was found in compound heterozygous state in sibs with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>) by <a href="#7" class="mim-tip-reference" title="Elleuch, N., Depienne, C., Benomar, A., Ouvrard Hernandez, A. M., Ferrer, X., Fontaine, B., Grid, D., Tallaksen, C. M. E., Zemmouri, R., Stevanin, G., Durr, A., Brice, A. <strong>Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia.</strong> Neurology 66: 654-659, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16534102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16534102</a>] [<a href="https://doi.org/10.1212/01.wnl.0000201185.91110.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16534102">Elleuch et al. (2006)</a>, see <a href="#0004">602783.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16534102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, SER692THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121918357 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918357;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121918357?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121918357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121918357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007217</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs, born of consanguineous Turkish parents, with complicated spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#18" class="mim-tip-reference" title="Warnecke, T., Duning, T., Schwan, A., Lohmann, H., Epplen, J. T., Young, P. <strong>A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation.</strong> Neurology 69: 368-375, 2007. Note: Erratum: Neurology 69: 1065 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17646629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17646629</a>] [<a href="https://doi.org/10.1212/01.wnl.0000266667.91074.fe" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17646629">Warnecke et al. (2007)</a> identified a homozygous 2075G-C transversion in exon 15 of the SPG7 gene, resulting in a ser692-to-thr (S692T) substitution. Age at onset ranged between 10 and 25 years, with lower limb spasticity, hyperreflexia, and cerebellar dysarthria. Unusual features included cognitive defects in executive function and attention, and supranuclear palsy. White matter abnormalities were evident in the spinal cord, frontal lobe, and midbrain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17646629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, LEU78TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121918358 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918358;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121918358?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121918358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121918358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007218 OR RCV000200640 OR RCV000664258 OR RCV001847594 OR RCV004752689 OR RCV004814852" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007218, RCV000200640, RCV000664258, RCV001847594, RCV004752689, RCV004814852" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007218...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected individuals from 2 presumably unrelated Italian families with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#1" class="mim-tip-reference" title="Arnoldi, A., Tonelli, A., Crippa, F., Villani, G., Pacelli, C., Sironi, M., Pozzoli, U., D'Angelo, M. G., Meola, G., Martinuzzi, A., Crimella, C., Redaelli, F., Panzeri, C., Renieri, A., Comi, G. P., Turconi, A. C., Bresolin, N., Bassi, M. T. <strong>A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.</strong> Hum. Mutat. 29: 522-531, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18200586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18200586</a>] [<a href="https://doi.org/10.1002/humu.20682" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18200586">Arnoldi et al. (2008)</a> identified a homozygous 233T-A transversion in exon 2 of the SPG7 gene, resulting in a leu78-to-ter (L78X) substitution. Haplotype analysis indicated a founder effect. All patients had adult onset of lower limb weakness and gait instability with relatively mild spasticity. One patient had mild cerebellar signs, and another had bladder dysfunction. Two sibs had mild cognitive deficits. Skeletal muscle biopsy of 1 patient showed ragged-red fibers, but detailed analysis of mitochondrial respiratory functions in all 3 patients showed a mild and heterogeneous patterns of dysfunction, excluding a specific defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18200586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 1-BP DEL, 1616C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs762795756 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs762795756;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs762795756?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs762795756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs762795756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000256054 OR RCV001848041 OR RCV001855011" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000256054, RCV001848041, RCV001855011" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000256054...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#1" class="mim-tip-reference" title="Arnoldi, A., Tonelli, A., Crippa, F., Villani, G., Pacelli, C., Sironi, M., Pozzoli, U., D'Angelo, M. G., Meola, G., Martinuzzi, A., Crimella, C., Redaelli, F., Panzeri, C., Renieri, A., Comi, G. P., Turconi, A. C., Bresolin, N., Bassi, M. T. <strong>A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.</strong> Hum. Mutat. 29: 522-531, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18200586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18200586</a>] [<a href="https://doi.org/10.1002/humu.20682" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18200586">Arnoldi et al. (2008)</a> identified compound heterozygosity for 2 mutations in the SPG7 gene: a 1-bp deletion (1616delC) and a 5.1-kb deletion (<a href="#0009">602783.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18200586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, 5.1-KB DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007220" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007220" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007220</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#1" class="mim-tip-reference" title="Arnoldi, A., Tonelli, A., Crippa, F., Villani, G., Pacelli, C., Sironi, M., Pozzoli, U., D'Angelo, M. G., Meola, G., Martinuzzi, A., Crimella, C., Redaelli, F., Panzeri, C., Renieri, A., Comi, G. P., Turconi, A. C., Bresolin, N., Bassi, M. T. <strong>A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.</strong> Hum. Mutat. 29: 522-531, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18200586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18200586</a>] [<a href="https://doi.org/10.1002/humu.20682" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18200586">Arnoldi et al. (2008)</a> identified compound heterozygosity for 2 mutations in the SPG7 gene: a 5.1-kb deletion, resulting in the deletion of exons 11, 12, and 13, and a 1-bp deletion (1616delC; <a href="#0008">602783.0008</a>). The 5.1-kb deletion appeared to be mediated by short interspersed nuclear element (SINE) retrotransposons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18200586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, GLY349SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs141659620 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs141659620;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs141659620?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs141659620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs141659620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007221 OR RCV000198037 OR RCV001847595 OR RCV002512867 OR RCV004515785 OR RCV004752690 OR RCV004814853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007221, RCV000198037, RCV001847595, RCV002512867, RCV004515785, RCV004752690, RCV004814853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007221...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#2" class="mim-tip-reference" title="Bonn, F., Pantakani, K., Shoukier, M., Langer, T., Mannan, A. U. <strong>Functional evaluation of paraplegin mutations by a yeast complementation assay.</strong> Hum. Mutat. 31: 617-621, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186691</a>] [<a href="https://doi.org/10.1002/humu.21226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20186691">Bonn et al. (2010)</a> identified compound heterozygosity for 2 mutations in the SPG7 gene: a 1045G-A transition in exon 8, resulting in a gly349-to-ser (G349S) substitution, and a 1749G-C transversion in exon 13, resulting in a trp583-to-cys (W583C; <a href="#0011">602783.0011</a>) substitution. The G349S mutation was found in 5 (0.7%) of 756 controls, and the W583C mutation was not found in 756 controls. In vitro complementation assay using mAAA protease-deficient yeast showed that the G349S and W583C variants had impaired proteolytic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, TRP583CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607085 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607085;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267607085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007222 OR RCV000996411" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007222, RCV000996411" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007222...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp583-to-cys (W583C) mutation in the SPG7 gene that was found in compound heterozygous state in 2 sibs with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>) by <a href="#2" class="mim-tip-reference" title="Bonn, F., Pantakani, K., Shoukier, M., Langer, T., Mannan, A. U. <strong>Functional evaluation of paraplegin mutations by a yeast complementation assay.</strong> Hum. Mutat. 31: 617-621, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186691</a>] [<a href="https://doi.org/10.1002/humu.21226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20186691">Bonn et al. (2010)</a>, see <a href="#0010">602783.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, ALA510VAL (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61755320;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs61755320</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs61755320 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61755320;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs61755320?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61755320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs61755320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034858 OR RCV000195683 OR RCV000198007 OR RCV000270813 OR RCV000515835 OR RCV000623796 OR RCV000626837 OR RCV000677252 OR RCV000850200 OR RCV001003619 OR RCV002463623 OR RCV003421943 OR RCV004814935" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034858, RCV000195683, RCV000198007, RCV000270813, RCV000515835, RCV000623796, RCV000626837, RCV000677252, RCV000850200, RCV001003619, RCV002463623, RCV003421943, RCV004814935" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034858...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 8 Spanish probands with autosomal recessive spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#16" class="mim-tip-reference" title="Sanchez-Ferrero, E., Coto, E., Beetz, C., Gamez, J., Corao, A. I., Diaz, M., Esteban, J., del Castillo, E., Moris, G., Infante, J., Menendez, M., Pascual-Pascual, S. I., Lopez de Munain, A., Garcia-Barcina, M. J., Alvarez, V. <strong>SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.</strong> Clin. Genet. 83: 257-262, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22571692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22571692</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01896.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22571692">Sanchez-Ferrero et al. (2013)</a> identified a 1529C-T transition in the SPG7 gene, resulting in an ala510-to-val (A510V) substitution at a highly conserved residue (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61755320;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs61755320</a>). Four patients carried the mutation in compound heterozygous state with another pathogenic mutation in the SPG7 gene, 1 patient was homozygous for A510V, and 3 patients carried A510V as a single heterozygous mutation. In the whole cohort, A510H was present in 8 (3%) of 285 Spanish patients with spastic paraplegia compared to 1% of controls. The findings suggested that A510H likely contributes to the pathogenesis of SPG7. <a href="#16" class="mim-tip-reference" title="Sanchez-Ferrero, E., Coto, E., Beetz, C., Gamez, J., Corao, A. I., Diaz, M., Esteban, J., del Castillo, E., Moris, G., Infante, J., Menendez, M., Pascual-Pascual, S. I., Lopez de Munain, A., Garcia-Barcina, M. J., Alvarez, V. <strong>SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.</strong> Clin. Genet. 83: 257-262, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22571692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22571692</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01896.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22571692">Sanchez-Ferrero et al. (2013)</a> noted that although A510V had initially been reported as a rare polymorphism, yeast complementation assays by <a href="#2" class="mim-tip-reference" title="Bonn, F., Pantakani, K., Shoukier, M., Langer, T., Mannan, A. U. <strong>Functional evaluation of paraplegin mutations by a yeast complementation assay.</strong> Hum. Mutat. 31: 617-621, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186691</a>] [<a href="https://doi.org/10.1002/humu.21226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20186691">Bonn et al. (2010)</a> showed that this missense change would perturb the proteolytic function of the heterooligomeric m-AAA protease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20186691+22571692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SPG7, MET1?
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003388959" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003388959" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003388959</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 57-year-old man, born to first-cousin Caucasian parents, with childhood optic nerve atrophy and spastic paraplegia-7 (SPG7; <a href="/entry/607259">607259</a>), <a href="#8" class="mim-tip-reference" title="Eriksen, K. O., Wigers, A. R., Wedding, I. M., Erichsen, A. K., Baroy, T., Soberg, K., Jorstad, O. K. <strong>A novel homozygous variant in the SPG7 gene presenting with childhood optic nerve atrophy.</strong> Am. J. Ophthal. Case Rep. 26: 101400, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35243150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35243150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35243150[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajoc.2022.101400" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35243150">Eriksen et al. (2022)</a> identified a homozygous c.2T-G transversion (c.2T-G, NM_003119.4) in the SPG7 gene, which alters the start codon (Met1?) and is expected to abolish production of paraplegin. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database (v2.1.1). Segregation analysis was not reported. The patient had onset of vision loss at age 6 years, but findings of spastic paraplegia were subtle and the diagnosis was not suspected until the likely pathogenic variant in the SPG7 gene was identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35243150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Arnoldi2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Arnoldi, A., Tonelli, A., Crippa, F., Villani, G., Pacelli, C., Sironi, M., Pozzoli, U., D'Angelo, M. G., Meola, G., Martinuzzi, A., Crimella, C., Redaelli, F., Panzeri, C., Renieri, A., Comi, G. P., Turconi, A. C., Bresolin, N., Bassi, M. T.
|
|
<strong>A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.</strong>
|
|
Hum. Mutat. 29: 522-531, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18200586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18200586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18200586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20682" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bonn2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bonn, F., Pantakani, K., Shoukier, M., Langer, T., Mannan, A. U.
|
|
<strong>Functional evaluation of paraplegin mutations by a yeast complementation assay.</strong>
|
|
Hum. Mutat. 31: 617-621, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.21226" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Casari1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A.
|
|
<strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong>
|
|
Cell 93: 973-983, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9635427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9635427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9635427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81203-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Crosby2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crosby, A. H., Proukakis, C.
|
|
<strong>Is the transportation highway the right road for hereditary spastic paraplegia? (Editorial)</strong>
|
|
Am. J. Hum. Genet. 71: 1009-1016, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355399</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/344206" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="De Michele1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Michele, G., De Fusco, M., Cavalcanti, F., Filla, A., Marconi, R., Volpe, G., Monticelli, A., Ballabio, A., Casari, G., Cocozza, S.
|
|
<strong>A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.</strong>
|
|
Am. J. Hum. Genet. 63: 135-139, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9634528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301930" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Durbin1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Durbin, H., Novelli, M., Bodmer, W.
|
|
<strong>Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR).</strong>
|
|
Genomics 19: 181-182, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7993411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7993411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7993411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Elleuch2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elleuch, N., Depienne, C., Benomar, A., Ouvrard Hernandez, A. M., Ferrer, X., Fontaine, B., Grid, D., Tallaksen, C. M. E., Zemmouri, R., Stevanin, G., Durr, A., Brice, A.
|
|
<strong>Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia.</strong>
|
|
Neurology 66: 654-659, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16534102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16534102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16534102" 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.0000201185.91110.15" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Eriksen2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksen, K. O., Wigers, A. R., Wedding, I. M., Erichsen, A. K., Baroy, T., Soberg, K., Jorstad, O. K.
|
|
<strong>A novel homozygous variant in the SPG7 gene presenting with childhood optic nerve atrophy.</strong>
|
|
Am. J. Ophthal. Case Rep. 26: 101400, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35243150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35243150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35243150[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=35243150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajoc.2022.101400" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Ferreirinha2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L., Casari, G., Ballabio, A., Rugarli, E. I.
|
|
<strong>Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport.</strong>
|
|
J. Clin. Invest. 113: 231-242, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722615[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=14722615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI20138" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Koppen2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koppen, M., Metodiev, M. D., Casari, G., Rugarli, E. I., Langer, T.
|
|
<strong>Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia.</strong>
|
|
Molec. Cell. Biol. 27: 758-767, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17101804[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=17101804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.01470-06" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Koyama1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koyama, K., Emi, M., Nakamura, Y.
|
|
<strong>The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis.</strong>
|
|
Genomics 16: 264-265, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8098008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8098008</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8098008" 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.1993.1173" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Mangion1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mangion, J., Rahman, N., Mansour, S., Brice, G., Rosbotham, J., Child, A. H., Murday, V. A., Mortimer, P. S., Barfoot, R., Sigurdsson, A., Edkins, S., Sarfarazi, M., Burnand, K., Evans, A. L., Nunan, T. O., Stratton, M. R., Jeffery, S.
|
|
<strong>A gene for lymphedema-distichiasis maps to 16q24.3.</strong>
|
|
Am. J. Hum. Genet. 65: 427-432, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302500" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Martinelli2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martinelli, P., La Mattina, V., Bernacchia, A., Magnoni, R., Cerri, F., Cox, G., Quattrini, A., Casari, G., Rugarli, E. I.
|
|
<strong>Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration.</strong>
|
|
Hum. Molec. Genet. 18: 2001-2013, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19289403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19289403</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19289403" 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/ddp124" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Pirozzi2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pirozzi, M., Quattrini, A., Andolfi, G., Dina, G., Malaguti, M. C., Auricchio, A., Rugarli, E. I.
|
|
<strong>Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia.</strong>
|
|
J. Clin. Invest. 116: 202-208, 2006. Note: Erratum: J. Clin. Invest. 124: 871 only, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357941</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16357941[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=16357941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI26210" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Pullman1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pullman, W. E., Bodmer, W. F.
|
|
<strong>Cloning and characterization of a gene that regulates cell adhesion.</strong>
|
|
Nature 356: 529-532, 1992. Note: Erratum: Nature 361: 564 only, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1560826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1560826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1560826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/356529a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Sanchez-Ferrero2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sanchez-Ferrero, E., Coto, E., Beetz, C., Gamez, J., Corao, A. I., Diaz, M., Esteban, J., del Castillo, E., Moris, G., Infante, J., Menendez, M., Pascual-Pascual, S. I., Lopez de Munain, A., Garcia-Barcina, M. J., Alvarez, V.
|
|
<strong>SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.</strong>
|
|
Clin. Genet. 83: 257-262, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22571692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22571692</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22571692" 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.1399-0004.2012.01896.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Settasatian1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Settasatian, C., Whitmore, S. A., Crawford, J., Bilton, R. L., Cleton-Jansen, A.-M., Sutherland, G. R., Callen, D. F.
|
|
<strong>Genomic structure and expression analysis of the spastic paraplegia gene, SPG7.</strong>
|
|
Hum. Genet. 105: 139-144, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10480368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10480368</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480368" 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/s004399900087" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Warnecke2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Warnecke, T., Duning, T., Schwan, A., Lohmann, H., Epplen, J. T., Young, P.
|
|
<strong>A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation.</strong>
|
|
Neurology 69: 368-375, 2007. Note: Erratum: Neurology 69: 1065 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17646629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17646629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17646629" 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.0000266667.91074.fe" 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">
|
|
Sonja A. Rasmussen - updated : 11/02/2023
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 4/10/2013<br>Cassandra L. Kniffin - updated : 8/30/2010<br>George E. Tiller - updated : 2/24/2010<br>Patricia A. Hartz - updated : 6/2/2009<br>Cassandra L. Kniffin - updated : 7/22/2008<br>Cassandra L. Kniffin - updated : 12/4/2007<br>Cassandra L. Kniffin - updated : 8/3/2007<br>Cassandra L. Kniffin - updated : 2/17/2006<br>Victor A. McKusick - updated : 2/10/2004<br>Victor A. McKusick - updated : 12/23/2002<br>Cassandra L. Kniffin - reorganized : 10/4/2002<br>Victor A. McKusick - updated : 8/23/1999
|
|
</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">
|
|
Stylianos E. Antonarakis : 7/8/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 11/02/2023
|
|
</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 : 03/15/2021<br>alopez : 07/22/2015<br>mcolton : 6/26/2015<br>mcolton : 5/7/2014<br>carol : 9/25/2013<br>carol : 5/14/2013<br>carol : 5/3/2013<br>carol : 4/23/2013<br>ckniffin : 4/10/2013<br>carol : 12/12/2012<br>wwang : 9/3/2010<br>ckniffin : 8/30/2010<br>wwang : 2/26/2010<br>terry : 2/24/2010<br>mgross : 6/2/2009<br>mgross : 6/2/2009<br>mgross : 6/2/2009<br>terry : 6/2/2009<br>carol : 10/15/2008<br>wwang : 7/29/2008<br>ckniffin : 7/22/2008<br>wwang : 12/6/2007<br>ckniffin : 12/5/2007<br>ckniffin : 12/4/2007<br>wwang : 8/21/2007<br>ckniffin : 8/3/2007<br>wwang : 3/17/2006<br>ckniffin : 2/17/2006<br>joanna : 3/19/2004<br>tkritzer : 2/16/2004<br>terry : 2/10/2004<br>carol : 10/15/2003<br>carol : 10/15/2003<br>mgross : 1/10/2003<br>tkritzer : 1/3/2003<br>tkritzer : 12/26/2002<br>terry : 12/23/2002<br>carol : 10/4/2002<br>ckniffin : 10/4/2002<br>ckniffin : 9/30/2002<br>carol : 8/28/2000<br>jlewis : 9/3/1999<br>terry : 8/23/1999<br>carol : 9/25/1998<br>carol : 9/14/1998<br>carol : 7/8/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 602783
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SPG7 MATRIX AAA PEPTIDASE SUBUNIT, PARAPLEGIN; SPG7
|
|
|
|
</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">
|
|
SPG7 GENE<br />
|
|
PARAPLEGIN; PGN<br />
|
|
CELL MATRIX ADHESION REGULATOR; CMAR<br />
|
|
CELL ADHESION REGULATOR; CAR
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SPG7</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 16q24.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 16:89,508,388-89,557,768 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
16q24.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Spastic paraplegia 7, autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
607259
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The SPG7 gene encodes paraplegin, a component of the m-AAA protease. The m-AAA protease is an ATP-dependent proteolytic complex of the mitochondrial inner membrane that degrades misfolded proteins and regulates ribosome assembly (Koppen et al., 2007). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Based on linkage analysis of a family with autosomal recessive spastic paraplegia that mapped to 16q24.3 (SPG7; 607259), Casari et al. (1998) used an EST clone to screen a human cDNA library and isolate a candidate gene. The full-length cDNA sequence corresponding to this gene encoded a deduced 795-amino acid protein, which they named paraplegin. Northern blot analysis detected a transcript of approximately 3.2 kb in all fetal and adult tissues tested. Two additional hybridizing transcripts of approximately 2.6 and 7.5 kb were detected in heart and pancreas. </p><p>Casari et al. (1998) concluded that the CAR gene identified by Pullman and Bodmer (1992) as a 459-bp transcript colinear with genomic DNA is part of the 3-prime untranscribed region of the SPG7 gene. Among other evidence supporting their conclusion, Casari et al. (1998) found a sequence 100% identical to the CAR sequence in over 30 different SPG7 clones, including ESTs, identified from many different cDNA libraries. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Settasatian et al. (1999) determined that the SPG7 gene contains 17 exons, ranging from 78 to 242 bp, and spans approximately 52 kb. The exon/intron boundaries and all splice junctions are consistent with consensus sequences for donor and acceptor sites. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genetic linkage analysis using a TaqI polymorphism in CEPH families, Koyama et al. (1993) demonstrated that CAR is close to D16S7 and D16S154, which are located in the 'peritelomeric' region of 16q. Mangion et al. (1999) stated that the CMAR gene maps to 16q24.3. </p><p>By positional cloning, De Michele et al. (1998) identified the SPG7 gene within the 16q24.3 critical region for autosomal recessive spastic paraplegia-7 (607259). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Pullman and Bodmer (1992) suggested that the CAR gene encodes an adhesion signal transduction molecule that functions in the suppression of tumor invasion. Casari et al. (1998) presented data calling this functional information into question. </p><p>Casari et al. (1998) determined that paraplegin is highly homologous to the yeast mitochondrial ATPases AFG3, RCA1, and YME1 (see 607472), which have both proteolytic and chaperone-like activities at the inner mitochondrial membrane. Immunofluorescence analysis and import experiments showed that paraplegin localizes to mitochondria. Analysis of muscle biopsies from 2 patients with paraplegin mutations showed typical signs of mitochondrial OXPHOS defects, thus suggesting a mechanism for neurodegeneration in SPG-type disorders. </p><p>Consistent with a role for paraplegin in mitochondrial function, muscle biopsies obtained from some patients with SPG7 mutations showed typical signs of mitochondrial disease (Casari et al., 1998). These included ragged-red fibers, intense succinate dehydrogenase-stained areas, and cytochrome oxidase-negative fibers. Furthermore, the degree of mitochondrial abnormality correlated with the severity of the disease. Taken together, these findings suggested that a mitochondrial-based mechanism underlies spastic paraplegia-7. Crosby and Proukakis (2002) cited preliminary reports of electron microscopy studies in mice lacking paraplegin that revealed that, long before degeneration, the axons were filled with abnormal mitochondria. Subsequently, swollen axons containing accumulated organelles and neurofilaments were seen, which suggested that mitochondrial dysfunction may lead to axonal degeneration by impairing axonal transport. Crosby and Proukakis (2002) concluded that aberrant cellular trafficking dynamics appears to be a common process responsible for the pattern of neurodegeneration seen in hereditary spastic paraplegia. </p><p>Using in vitro protein binding assays and immunoprecipitation analysis, Koppen et al. (2007) showed that paraplegin interacted with AFG3L2 (604581) in the m-AAA protease complex. Paraplegin did not interact with itself. Loss of paraplegin in Spg7 -/- mice or in SPG7 patient fibroblasts resulted in m-AAA protease complexes made up of only homodimerized AFG3L2 that were proteolytically active in yeast complementation assays. Bonn et al. (2010) used the yeast complementation assay to evaluate the functional consequences of pathogenic mutations (see, e.g., 602783.0010 and 602783.0011) in the SPG7 gene. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Casari et al. (1998) found that all affected individuals from the SPG7 family reported by De Michele et al. (1998) were homozygous for a 9.5-kb deletion (602783.0003) in the SPG7 gene. In 2 additional unrelated families with autosomal recessive SPG, 1 demonstrating a pure form of the disorder and 1 demonstrating a complicated form of the disorder, Casari et al. (1998) identified 2 additional homozygous paraplegin mutations (602783.0001-602783.0002), both resulting in a frameshift and a truncated protein. </p><p>Koyama et al. (1993) identified an insertion/deletion polymorphism in the coding region of the CMAR gene; the variant was detected in 9 chromosomes among 30 unrelated Japanese individuals. Durbin et al. (1994) detected a 4-bp insertion (CACA) at nucleotide 241 of the CMAR gene. Casari et al. (1998) noted that the polymorphisms identified by Koyama et al. (1993) and Durbin et al. (1994) would result in major changes in the CMAR putative protein product, suggesting that the original CMAR cDNA clone may not encode a protein in vivo and that functional data obtained using CMAR cDNA in transfection experiments may be due to artifactual translation of a peptide encoded by the CMAR sequence. </p><p>In 1 (0.7%) of 136 index patients with autosomal recessive SPG, Elleuch et al. (2006) identified 2 mutations in the SPG7 gene (602783.0004-602783.0005). Twenty families had at least 1 variant in the SPG7 gene that was not found in 550 control chromosomes. In 4 of these families, mutations were predicted to be highly deleterious, suggesting that they may have contributed to the phenotype. The authors identified several additional rare variants in the SPG7 gene, which were of undetermined significance. </p><p>Arnoldi et al. (2008) identified 7 different SPG7 mutations (see, e.g., 602783.0007-602783.0009) in 6 (4.4%) of 135 Italian patients with spastic paraplegia. Four of the patients were heterozygous for the mutations, which fell within conserved domains of the protein and were not found in controls. </p><p>Sanchez-Ferrero et al. (2013) sequenced the SPG7 gene in 285 Spanish patients with spastic paraplegia who were negative for mutations in the SPG4 (604277) and SPG3A (606439) genes. Fourteen SPG7 mutations, including 12 novel mutations, were identified in 14 patients. The mutations included 2 large deletions, 5 missense changes, 4 nonsense mutations, 2 frameshift insertion/deletions, and 1 splice site mutation. Thirteen patients had only a single heterozygous mutation, suggesting a dominant effect for some SPG7 mutations. Functional studies were not performed to assess the biologic significance. An A510V substitution (602783.0012) was found in 8 patients (3%): 4 carried A510V in compound heterozygous state with another SPG7 mutation, 1 was homozygous for A510V, and 3 patients were heterozygous for A510V. The A510V substitution was also identified in 1% of controls. All patients had adult onset of the disorder, but only 35% had a complicated phenotype. </p><p>In a 57-year-old man, born to first-cousin Caucasian parents, with childhood optic nerve atrophy and SPG7, Eriksen et al. (2022) identified a homozygous mutation in the SPG7 gene (M1?; 602783.0013), which alters the start codon and is expected to abolish production of paraplegin. The patient had onset of vision loss at age 6 years, but findings of spastic paraplegia were subtle and the diagnosis was not suspected until the likely pathogenic variant in the SPG7 gene was identified. The authors noted that the SPG7 gene should be added to the workup of suspected hereditary optic neuropathy. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
|
|
Because the SPG7 gene was mapped to chromosome 16q24.3, a region of frequent loss of heterozygosity (LOH) in sporadic breast and prostate cancer, Settasatian et al. (1999) performed SSCP analysis of 10 exons of this gene in a number of sporadic breast cancer samples showing LOH at 16q24.3. No mutations were detected; only SNPs were observed in 1 exon and 3 introns. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ferreirinha et al. (2004) developed a mouse model for autosomal recessive hereditary spastic paraplegia due to mutation in the SPG7 gene, which encodes the mitochondrial ATPase paraplegin. Paraplegin-deficient mice were affected by a distal axonopathy of spinal and peripheral axons, characterized by axonal swelling and degeneration. Ferreirinha et al. (2004) found that mitochondrial morphologic abnormalities occurred in synaptic terminals and in distal regions of axons long before the first signs of swelling and degeneration and correlated with onset of motor impairment. Axonal swellings occurred through massive accumulation of organelles and neurofilaments, suggesting impairment of anterograde axonal transport. Retrograde axonal transport was delayed in symptomatic mice. Ferreirinha et al. (2004) speculated that local failure of mitochondrial function may affect axonal transport and cause axonal degeneration. They concluded that a timely therapeutic intervention might prevent the loss of axons. </p><p>In Spg7-null mice, Pirozzi et al. (2006) found that intramuscular delivery of adeno-associated virus vector containing Spg7 halted the progression of neuropathologic changes and rescued disease-associated morphologic changes in the mitochondria of peripheral nerves. A single injection before onset of symptoms improved motor performance of mice for up to 10 months, suggesting that peripheral neuropathy contributes to the clinical phenotype. </p><p>Martinelli et al. (2009) reported an early-onset severe neurologic phenotype in Spg7-null/Afg3l2 +/- double-mutant mice characterized by loss of balance, tremor, and ataxia. Double-mutant mice displayed acceleration and worsening of the axonopathy observed in Spg7-null mice. In addition, they showed prominent cerebellar degeneration with loss of Purkinje cells and parallel fibers, and reactive astrogliosis. Mitochondria from affected tissues were prone to lose mtDNA and had unstable respiratory complexes. At late stages, neurons contained structural abnormal mitochondria defective in COX-SDH reaction. Martinelli et al. (2009) suggested that different neuronal populations may have variable thresholds of susceptibility to reduced levels of the m-AAA protease, and that impaired mitochondrial proteolysis may be a mechanism of cerebellar degeneration. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>13 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 2-BP DEL, NT784
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs768136171,
|
|
|
|
|
|
gnomAD: rs768136171,
|
|
|
|
|
|
ClinVar: RCV000615294, RCV000989664, RCV003403411, RCV005000374
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 2 brothers from a small village in southern Italy who had autosomal recessive hereditary pure spastic paraplegia (SPG7; 607259), Casari et al. (1998) identified a 2-bp deletion (784del2) in the SPG7 gene. This mutation causes a frameshift that abolishes approximately 60% of the protein. The patient, who showed typical signs of pure SPG with an age of onset of 26 years, was homozygous for this mutation; consanguinity was very likely. The other brother was unavailable for study. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 1-BP INS, 2228A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs763126378,
|
|
|
|
|
|
gnomAD: rs763126378,
|
|
|
|
|
|
ClinVar: RCV001091058, RCV001760064
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Casari et al. (1998) found a mutation in the SPG7 gene in a French family in which complicated SPG segregated as an autosomal recessive trait (SPG7; 607259). Patients from this family were affected by a form of SPG with a mean age of onset of 34 years. They showed progressive weakness and spasticity of the lower limbs, decreased perception of sharp stimulation, diminished vibratory sense, and urinary incontinence, which are typical signs of SPG. These patients also had optic atrophy (3 of 3 examined), cortical atrophy (1 of 3 examined), and cerebellar atrophy (2 of 3 examined). All affected sibs from this family were homozygous for an A insertion at position 2228 of the paraplegin cDNA, while their mother was heterozygous for the same mutation. This insertion creates a frameshift and a stop codon only 2 amino acids downstream, resulting in a truncated form of paraplegin that is missing 57 amino acids at the C terminus. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 9.5-KB DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000007214
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Casari et al. (1998) found that all affected individuals from the family with autosomal recessive spastic paraplegia-7 (SPG7; 607259) reported by De Michele et al. (1998) were homozygous for a 9.5-kb deletion in the SPG7 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 2-BP DEL, 1-BP INS, 850
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs768595656,
|
|
|
|
|
|
gnomAD: rs768595656,
|
|
|
|
|
|
ClinVar: RCV000640978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected sibs of a Moroccan family with autosomal recessive spastic paraplegia-7 (SPG7; 607259), Elleuch et al. (2006) identified compound heterozygosity for 2 mutations in the SPG7 gene. One allele had a 2-bp deletion and 1-bp insertion (850delTTinsC), resulting in premature termination of the protein. The second allele had an in-frame deletion (1742delTGG; 602783.0005), resulting in the deletion of val581. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 3-BP DEL, 1742TGG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1597661607,
|
|
|
|
|
|
|
|
ClinVar: RCV000007216
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the in-frame deletion in the SPG7 gene (1742delTGG) that was found in compound heterozygous state in sibs with autosomal recessive spastic paraplegia-7 (SPG7; 607259) by Elleuch et al. (2006), see 602783.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, SER692THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918357,
|
|
|
|
|
|
gnomAD: rs121918357,
|
|
|
|
|
|
ClinVar: RCV000007217
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs, born of consanguineous Turkish parents, with complicated spastic paraplegia-7 (SPG7; 607259), Warnecke et al. (2007) identified a homozygous 2075G-C transversion in exon 15 of the SPG7 gene, resulting in a ser692-to-thr (S692T) substitution. Age at onset ranged between 10 and 25 years, with lower limb spasticity, hyperreflexia, and cerebellar dysarthria. Unusual features included cognitive defects in executive function and attention, and supranuclear palsy. White matter abnormalities were evident in the spinal cord, frontal lobe, and midbrain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, LEU78TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918358,
|
|
|
|
|
|
gnomAD: rs121918358,
|
|
|
|
|
|
ClinVar: RCV000007218, RCV000200640, RCV000664258, RCV001847594, RCV004752689, RCV004814852
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected individuals from 2 presumably unrelated Italian families with autosomal recessive spastic paraplegia-7 (SPG7; 607259), Arnoldi et al. (2008) identified a homozygous 233T-A transversion in exon 2 of the SPG7 gene, resulting in a leu78-to-ter (L78X) substitution. Haplotype analysis indicated a founder effect. All patients had adult onset of lower limb weakness and gait instability with relatively mild spasticity. One patient had mild cerebellar signs, and another had bladder dysfunction. Two sibs had mild cognitive deficits. Skeletal muscle biopsy of 1 patient showed ragged-red fibers, but detailed analysis of mitochondrial respiratory functions in all 3 patients showed a mild and heterogeneous patterns of dysfunction, excluding a specific defect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 1-BP DEL, 1616C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs762795756,
|
|
|
|
|
|
gnomAD: rs762795756,
|
|
|
|
|
|
ClinVar: RCV000256054, RCV001848041, RCV001855011
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with autosomal recessive spastic paraplegia-7 (SPG7; 607259), Arnoldi et al. (2008) identified compound heterozygosity for 2 mutations in the SPG7 gene: a 1-bp deletion (1616delC) and a 5.1-kb deletion (602783.0009). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, 5.1-KB DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000007220
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with autosomal recessive spastic paraplegia-7 (SPG7; 607259), Arnoldi et al. (2008) identified compound heterozygosity for 2 mutations in the SPG7 gene: a 5.1-kb deletion, resulting in the deletion of exons 11, 12, and 13, and a 1-bp deletion (1616delC; 602783.0008). The 5.1-kb deletion appeared to be mediated by short interspersed nuclear element (SINE) retrotransposons. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, GLY349SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs141659620,
|
|
|
|
|
|
gnomAD: rs141659620,
|
|
|
|
|
|
ClinVar: RCV000007221, RCV000198037, RCV001847595, RCV002512867, RCV004515785, RCV004752690, RCV004814853
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with autosomal recessive spastic paraplegia-7 (SPG7; 607259), Bonn et al. (2010) identified compound heterozygosity for 2 mutations in the SPG7 gene: a 1045G-A transition in exon 8, resulting in a gly349-to-ser (G349S) substitution, and a 1749G-C transversion in exon 13, resulting in a trp583-to-cys (W583C; 602783.0011) substitution. The G349S mutation was found in 5 (0.7%) of 756 controls, and the W583C mutation was not found in 756 controls. In vitro complementation assay using mAAA protease-deficient yeast showed that the G349S and W583C variants had impaired proteolytic function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, TRP583CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607085,
|
|
|
|
|
|
|
|
ClinVar: RCV000007222, RCV000996411
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp583-to-cys (W583C) mutation in the SPG7 gene that was found in compound heterozygous state in 2 sibs with autosomal recessive spastic paraplegia-7 (SPG7; 607259) by Bonn et al. (2010), see 602783.0010. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, ALA510VAL ({dbSNP rs61755320})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61755320,
|
|
|
|
|
|
gnomAD: rs61755320,
|
|
|
|
|
|
ClinVar: RCV000034858, RCV000195683, RCV000198007, RCV000270813, RCV000515835, RCV000623796, RCV000626837, RCV000677252, RCV000850200, RCV001003619, RCV002463623, RCV003421943, RCV004814935
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 8 Spanish probands with autosomal recessive spastic paraplegia-7 (SPG7; 607259), Sanchez-Ferrero et al. (2013) identified a 1529C-T transition in the SPG7 gene, resulting in an ala510-to-val (A510V) substitution at a highly conserved residue (rs61755320). Four patients carried the mutation in compound heterozygous state with another pathogenic mutation in the SPG7 gene, 1 patient was homozygous for A510V, and 3 patients carried A510V as a single heterozygous mutation. In the whole cohort, A510H was present in 8 (3%) of 285 Spanish patients with spastic paraplegia compared to 1% of controls. The findings suggested that A510H likely contributes to the pathogenesis of SPG7. Sanchez-Ferrero et al. (2013) noted that although A510V had initially been reported as a rare polymorphism, yeast complementation assays by Bonn et al. (2010) showed that this missense change would perturb the proteolytic function of the heterooligomeric m-AAA protease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPG7, MET1?
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003388959
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 57-year-old man, born to first-cousin Caucasian parents, with childhood optic nerve atrophy and spastic paraplegia-7 (SPG7; 607259), Eriksen et al. (2022) identified a homozygous c.2T-G transversion (c.2T-G, NM_003119.4) in the SPG7 gene, which alters the start codon (Met1?) and is expected to abolish production of paraplegin. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database (v2.1.1). Segregation analysis was not reported. The patient had onset of vision loss at age 6 years, but findings of spastic paraplegia were subtle and the diagnosis was not suspected until the likely pathogenic variant in the SPG7 gene was identified. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arnoldi, A., Tonelli, A., Crippa, F., Villani, G., Pacelli, C., Sironi, M., Pozzoli, U., D'Angelo, M. G., Meola, G., Martinuzzi, A., Crimella, C., Redaelli, F., Panzeri, C., Renieri, A., Comi, G. P., Turconi, A. C., Bresolin, N., Bassi, M. T.
|
|
<strong>A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.</strong>
|
|
Hum. Mutat. 29: 522-531, 2008.
|
|
|
|
|
|
[PubMed: 18200586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20682]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bonn, F., Pantakani, K., Shoukier, M., Langer, T., Mannan, A. U.
|
|
<strong>Functional evaluation of paraplegin mutations by a yeast complementation assay.</strong>
|
|
Hum. Mutat. 31: 617-621, 2010.
|
|
|
|
|
|
[PubMed: 20186691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.21226]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., Ballabio, A.
|
|
<strong>Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.</strong>
|
|
Cell 93: 973-983, 1998.
|
|
|
|
|
|
[PubMed: 9635427]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81203-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crosby, A. H., Proukakis, C.
|
|
<strong>Is the transportation highway the right road for hereditary spastic paraplegia? (Editorial)</strong>
|
|
Am. J. Hum. Genet. 71: 1009-1016, 2002.
|
|
|
|
|
|
[PubMed: 12355399]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/344206]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Michele, G., De Fusco, M., Cavalcanti, F., Filla, A., Marconi, R., Volpe, G., Monticelli, A., Ballabio, A., Casari, G., Cocozza, S.
|
|
<strong>A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.</strong>
|
|
Am. J. Hum. Genet. 63: 135-139, 1998.
|
|
|
|
|
|
[PubMed: 9634528]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301930]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Durbin, H., Novelli, M., Bodmer, W.
|
|
<strong>Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR).</strong>
|
|
Genomics 19: 181-182, 1994.
|
|
|
|
|
|
[PubMed: 7993411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elleuch, N., Depienne, C., Benomar, A., Ouvrard Hernandez, A. M., Ferrer, X., Fontaine, B., Grid, D., Tallaksen, C. M. E., Zemmouri, R., Stevanin, G., Durr, A., Brice, A.
|
|
<strong>Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia.</strong>
|
|
Neurology 66: 654-659, 2006.
|
|
|
|
|
|
[PubMed: 16534102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000201185.91110.15]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eriksen, K. O., Wigers, A. R., Wedding, I. M., Erichsen, A. K., Baroy, T., Soberg, K., Jorstad, O. K.
|
|
<strong>A novel homozygous variant in the SPG7 gene presenting with childhood optic nerve atrophy.</strong>
|
|
Am. J. Ophthal. Case Rep. 26: 101400, 2022.
|
|
|
|
|
|
[PubMed: 35243150]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajoc.2022.101400]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L., Casari, G., Ballabio, A., Rugarli, E. I.
|
|
<strong>Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport.</strong>
|
|
J. Clin. Invest. 113: 231-242, 2004.
|
|
|
|
|
|
[PubMed: 14722615]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI20138]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koppen, M., Metodiev, M. D., Casari, G., Rugarli, E. I., Langer, T.
|
|
<strong>Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia.</strong>
|
|
Molec. Cell. Biol. 27: 758-767, 2007.
|
|
|
|
|
|
[PubMed: 17101804]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.01470-06]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koyama, K., Emi, M., Nakamura, Y.
|
|
<strong>The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis.</strong>
|
|
Genomics 16: 264-265, 1993.
|
|
|
|
|
|
[PubMed: 8098008]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1173]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mangion, J., Rahman, N., Mansour, S., Brice, G., Rosbotham, J., Child, A. H., Murday, V. A., Mortimer, P. S., Barfoot, R., Sigurdsson, A., Edkins, S., Sarfarazi, M., Burnand, K., Evans, A. L., Nunan, T. O., Stratton, M. R., Jeffery, S.
|
|
<strong>A gene for lymphedema-distichiasis maps to 16q24.3.</strong>
|
|
Am. J. Hum. Genet. 65: 427-432, 1999.
|
|
|
|
|
|
[PubMed: 10417285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302500]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martinelli, P., La Mattina, V., Bernacchia, A., Magnoni, R., Cerri, F., Cox, G., Quattrini, A., Casari, G., Rugarli, E. I.
|
|
<strong>Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration.</strong>
|
|
Hum. Molec. Genet. 18: 2001-2013, 2009.
|
|
|
|
|
|
[PubMed: 19289403]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp124]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pirozzi, M., Quattrini, A., Andolfi, G., Dina, G., Malaguti, M. C., Auricchio, A., Rugarli, E. I.
|
|
<strong>Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia.</strong>
|
|
J. Clin. Invest. 116: 202-208, 2006. Note: Erratum: J. Clin. Invest. 124: 871 only, 2014.
|
|
|
|
|
|
[PubMed: 16357941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI26210]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pullman, W. E., Bodmer, W. F.
|
|
<strong>Cloning and characterization of a gene that regulates cell adhesion.</strong>
|
|
Nature 356: 529-532, 1992. Note: Erratum: Nature 361: 564 only, 1993.
|
|
|
|
|
|
[PubMed: 1560826]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/356529a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sanchez-Ferrero, E., Coto, E., Beetz, C., Gamez, J., Corao, A. I., Diaz, M., Esteban, J., del Castillo, E., Moris, G., Infante, J., Menendez, M., Pascual-Pascual, S. I., Lopez de Munain, A., Garcia-Barcina, M. J., Alvarez, V.
|
|
<strong>SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.</strong>
|
|
Clin. Genet. 83: 257-262, 2013.
|
|
|
|
|
|
[PubMed: 22571692]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2012.01896.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Settasatian, C., Whitmore, S. A., Crawford, J., Bilton, R. L., Cleton-Jansen, A.-M., Sutherland, G. R., Callen, D. F.
|
|
<strong>Genomic structure and expression analysis of the spastic paraplegia gene, SPG7.</strong>
|
|
Hum. Genet. 105: 139-144, 1999.
|
|
|
|
|
|
[PubMed: 10480368]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004399900087]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warnecke, T., Duning, T., Schwan, A., Lohmann, H., Epplen, J. T., Young, P.
|
|
<strong>A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation.</strong>
|
|
Neurology 69: 368-375, 2007. Note: Erratum: Neurology 69: 1065 only, 2007.
|
|
|
|
|
|
[PubMed: 17646629]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000266667.91074.fe]
|
|
|
|
|
|
</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">
|
|
Sonja A. Rasmussen - updated : 11/02/2023<br>Cassandra L. Kniffin - updated : 4/10/2013<br>Cassandra L. Kniffin - updated : 8/30/2010<br>George E. Tiller - updated : 2/24/2010<br>Patricia A. Hartz - updated : 6/2/2009<br>Cassandra L. Kniffin - updated : 7/22/2008<br>Cassandra L. Kniffin - updated : 12/4/2007<br>Cassandra L. Kniffin - updated : 8/3/2007<br>Cassandra L. Kniffin - updated : 2/17/2006<br>Victor A. McKusick - updated : 2/10/2004<br>Victor A. McKusick - updated : 12/23/2002<br>Cassandra L. Kniffin - reorganized : 10/4/2002<br>Victor A. McKusick - updated : 8/23/1999
|
|
</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">
|
|
Stylianos E. Antonarakis : 7/8/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 11/02/2023<br>carol : 03/15/2021<br>alopez : 07/22/2015<br>mcolton : 6/26/2015<br>mcolton : 5/7/2014<br>carol : 9/25/2013<br>carol : 5/14/2013<br>carol : 5/3/2013<br>carol : 4/23/2013<br>ckniffin : 4/10/2013<br>carol : 12/12/2012<br>wwang : 9/3/2010<br>ckniffin : 8/30/2010<br>wwang : 2/26/2010<br>terry : 2/24/2010<br>mgross : 6/2/2009<br>mgross : 6/2/2009<br>mgross : 6/2/2009<br>terry : 6/2/2009<br>carol : 10/15/2008<br>wwang : 7/29/2008<br>ckniffin : 7/22/2008<br>wwang : 12/6/2007<br>ckniffin : 12/5/2007<br>ckniffin : 12/4/2007<br>wwang : 8/21/2007<br>ckniffin : 8/3/2007<br>wwang : 3/17/2006<br>ckniffin : 2/17/2006<br>joanna : 3/19/2004<br>tkritzer : 2/16/2004<br>terry : 2/10/2004<br>carol : 10/15/2003<br>carol : 10/15/2003<br>mgross : 1/10/2003<br>tkritzer : 1/3/2003<br>tkritzer : 12/26/2002<br>terry : 12/23/2002<br>carol : 10/4/2002<br>ckniffin : 10/4/2002<br>ckniffin : 9/30/2002<br>carol : 8/28/2000<br>jlewis : 9/3/1999<br>terry : 8/23/1999<br>carol : 9/25/1998<br>carol : 9/14/1998<br>carol : 7/8/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|