6089 lines
548 KiB
Text
6089 lines
548 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
|
|
|
|
- *311770 - PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS A PROTEIN; PIGA
|
|
|
|
|
|
- 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=311770"><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">*311770</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="#geneFamily">Gene Family</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/311770">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=ENSG00000165195;t=ENST00000333590" 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=5277" 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=311770" 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=ENSG00000165195;t=ENST00000333590" 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_002641,NM_020473,NR_033835,NR_033836,XM_011545539" 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_002641" 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=311770" 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=02410&isoform_id=02410_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/PIGA" 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/219994,585696,1132481,4261629,4261860,6010208,11863130,23398601,119619285,119619286,119619287,119619288,119619289,119619290,158254426,189054687,193783658,194382788,194385320,299782546,768032528,1335348149,1335348151,1335348153,1335348155,1335348157,1335348159,1335348161,1335348163,1335348165,1335348167,1335348169,1335348171,1335348173,1335348175,1335348177,1335348179,1335348181,1335348183,1335348185,1335348187,1335348189,1335348191,1335348193,1335348195,1335348197,1335348199,1335348201,1335348203,1335348205,1335348207,1335348209,1335348211,1335348213,1335348215,1335348217,1335348219,1335348221,1335348223,1335348225,1335348227,1335348229,1335348231,1335348233,1335348235,1335348237,1335348239,1335348241,1335348243,1335348245,1335348247,1335348249,1335348251,1335348253,1335348255,1335348257,1335348259,1335348261,1335348263,1335348265,1335348267,1335348269,1335348271,1335348273,1335348275,1335348277,1335348279,1335348281,1335348283,1335348285,1335348287,1335348289,1335348291,1335348293,1335348295,1335348297,1335348299,1335348301,1335348303,1335348305,1335348307,1335348309,1335348311,1335348313,1335348315,1335348317,1335348319,1335348321,1335348323,1335348325,1335348327,1335348329,1335348331,1335348333,1335348335,1335348337,1335348339,1335348341,1335348343,1335348345,1335348347,1335348349,1335348351,1335348353,1335348355,1335348357,1335348359,1335348361,1335348363,1335348365,1335348367,1335348369,1335348371,1335348373,1335348375,1335348377,1335348379,1335348381,1335348383,1335348385,1335348387,1335348389,1335348391,1335348393,1335348395,1335348397,2462629762" 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/P37287" 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=5277" 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=ENSG00000165195;t=ENST00000333590" 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=PIGA" 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=PIGA" 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+5277" 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/PIGA" 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:5277" 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/5277" 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=chrX&hgg_gene=ENST00000333590.6&hgg_start=15319451&hgg_end=15335554&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:8957" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:8957" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimMedlinePlusGeneticsFold" id="mimMedlinePlusGeneticsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Consumer-friendly information about the effects of genetic variation on human health."><span id="mimMedlinePlusGeneticsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>MedlinePlus Genetics</div>
|
|
<div id="mimMedlinePlusGeneticsFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/condition/paroxysmal-nocturnal-hemoglobinuria" title="Paroxysmal nocturnal hemoglobinuria" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">Paroxysmal nocturnal hemog… </a></div><div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/gene/piga" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">PIGA gene </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=311770[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=311770[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/PIGA/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/ENSG00000165195" 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.gwascentral.org/search?q=PIGA" 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=PIGA" 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="http://www.LOVD.nl/PIGA" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PIGA&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/PA33288" 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:8957" 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/FBgn0034270.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:99461" 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/PIGA#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:99461" 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/5277/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002372/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=5277" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00008431;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-040426-1086" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5277" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=PIGA&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 1963002, 774151000<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> D59.5<br />
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
311770
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS A PROTEIN; PIGA
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS A PROTEIN, PSEUDOGENE 1, INCLUDED; PIGAP1, INCLUDED; PIGAP, INCLUDED
|
|
</span>
|
|
</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=PIGA" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PIGA</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/X/78?start=-3&limit=10&highlight=78">Xp22.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:15319451-15335554&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'})">X:15,319,451-15,335,554</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=300868,301072,300818" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/78?start=-3&limit=10&highlight=78">
|
|
Xp22.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Multiple congenital anomalies-hypotonia-seizures syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300868"> 300868 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Neurodevelopmental disorder with epilepsy and hemochromatosis
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/301072"> 301072 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Paroxysmal nocturnal hemoglobinuria, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300818"> 300818 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</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/311770" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/311770" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<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>Glycosylphosphatidylinositol (GPI) is a glycolipid that attaches dozens of different proteins to the cell surface. PIGA is 1 of several proteins required for the first step of GPI anchor biosynthesis (review by <a href="#5" class="mim-tip-reference" title="Brodsky, R. A. <strong>Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria.</strong> Blood Rev. 22: 65-74, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18063459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18063459</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18063459[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.blre.2007.10.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18063459">Brodsky, 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18063459" 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>For further information on the PIG gene family and GPI biosynthesis, see GENE FAMILY.</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>Some of the genes involved in GPI biosynthesis are represented by different complementation classes of GPI anchor-deficient mutant cells derived from human and rodent cell lines (<a href="#30" class="mim-tip-reference" title="Stevens, V. L., Raetz, C. R. H. <strong>Defective glycosyl phosphatidylinositol biosynthesis in extracts of three thy-1 negative lymphoma cell mutants.</strong> J. Biol. Chem. 266: 10039-10042, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1828068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1828068</a>]" pmid="1828068">Stevens and Raetz, 1991</a>; <a href="#31" class="mim-tip-reference" title="Sugiyama, E., DeGasperi, R., Urakaze, M., Chang, H.-M., Thomas, L. J., Hyman, R., Warren, C. D., Yeh, E. T. H. <strong>Identification of defects in glycosylphosphatidylinositol anchor biosynthesis in the thy-1 expression mutants.</strong> J. Biol. Chem. 266: 12119-12122, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1829456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1829456</a>]" pmid="1829456">Sugiyama et al., 1991</a>; <a href="#8" class="mim-tip-reference" title="Hirose, S., Mohney, R. P., Mutka, S. C., Ravi, L., Singleton, D. R., Perry, G., Tartakoff, A. M., Medof, M. E. <strong>Derivation and characterization of glycoinositol-phospholipid anchor-defective human K562 cell clones.</strong> J. Biol. Chem. 267: 5272-5278, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1371997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1371997</a>]" pmid="1371997">Hirose et al., 1992</a>). By expression cloning using a GPI anchor-deficient human B-lymphoblastoid cell line belonging to complementation class A, <a href="#18" class="mim-tip-reference" title="Miyata, T., Takeda, J., Iida, Y., Yamada, N., Inoue, N., Takahashi, M., Maeda, K., Kitani, T., Kinoshita, T. <strong>The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.</strong> Science 259: 1318-1320, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7680492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7680492</a>] [<a href="https://doi.org/10.1126/science.7680492" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7680492">Miyata et al. (1993)</a> cloned PIGA. The predicted 484-amino acid PIGA protein has a single transmembrane domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1371997+7680492+1829456+1828068" 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="Kawagoe, K., Takeda, J., Endo, Y., Kinoshita, T. <strong>Molecular cloning of murine Pig-a, a gene for GPI-anchor biosynthesis, and demonstration of interspecies conservation of its structure, function, and genetic locus.</strong> Genomics 23: 566-574, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851884</a>] [<a href="https://doi.org/10.1006/geno.1994.1544" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7851884">Kawagoe et al. (1994)</a> reported that the deduced amino acid sequence of the mouse Piga protein is 88% identical to that of the human protein. Database analysis demonstrated that a yeast gene, Spt14, is homologous and that these genes are members of a glycosyltransferase gene family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The PIGA gene encodes 4 isoforms, 2 coding and 2 noncoding. <a href="#2" class="mim-tip-reference" title="Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G. <strong>Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.</strong> Hum. Mutat. 35: 350-355, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357517</a>] [<a href="https://doi.org/10.1002/humu.22498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357517">Belet et al. (2014)</a> found that the major isoform encodes a 484-residue protein that starts in and includes exon 2 and was expressed in all tested human tissues. The second coding isoform starts in exon 1, but skips exon 2 and produces a truncated protein of 250 residues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24357517" 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>PIGA Pseudogene 1</em></strong></p><p>
|
|
In the course of analyses of PIGA genetic alterations in patients with paroxysmal nocturnal hemoglobinuria (PNH; <a href="/entry/300818">300818</a>) (see MOLECULAR GENETICS), <a href="#42" class="mim-tip-reference" title="Yu, J., Nagarajan, S., Ueda, E., Knez, J. J., Petersen, R. B., Medof, M. E. <strong>Characterization of alternatively spliced PIG-A transcripts in normal and paroxysmal nocturnal hemoglobinuria cells.</strong> Braz. J. Med. Biol. Res. 27: 195-201, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081230</a>]" pmid="8081230">Yu et al. (1994)</a> amplified PIGA transcripts expressed in affected lymphocytes by RT-PCR and unexpectedly found a product differing from the authentic PIGA product by 126 nucleotide exchanges and 5 deletions in the coding region. <a href="#25" class="mim-tip-reference" title="Nagarajan, S., Brown, C. J., Medof, M. E. <strong>Identification of a PIG-A related processed gene on chromosome 12.</strong> Hum. Genet. 95: 691-697, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7654280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7654280</a>] [<a href="https://doi.org/10.1007/BF00209489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7654280">Nagarajan et al. (1995)</a> showed that mRNA with this sequence was coexpressed with PIGA mRNA in a wide range of cell types. Mapping of genomic DNA from human/rodent hybrids showed that the sequence derived from an intronless processed gene (PIGAP) on chromosome 12. Duplicated processed genes had been described for a number of X-linked genes, including pyruvate dehydrogenase (<a href="/entry/300502">300502</a>), the adenine nucleotide translocase genes (<a href="/entry/300150">300150</a> and <a href="/entry/300151">300151</a>), and phosphoglycerate kinase (<a href="/entry/311800">311800</a>). The identification of a stop codon at position 243 in the mRNA sequence of the PIGAP gene on chromosome 12 indicates that if this mRNA is translated, its protein product is probably not functional. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8081230+7654280" 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="#10" class="mim-tip-reference" title="Iida, Y., Takeda, J., Miyata, T., Inoue, N., Nishimura, J., Kitani, T., Maeda, K., Kinoshita, T. <strong>Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria.</strong> Blood 83: 3126-3131, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8193350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8193350</a>]" pmid="8193350">Iida et al. (1994)</a> reported that the PIGA gene is at least 17 kb long and has 6 exons. They sequenced the exon-intron boundaries and described the characteristics of the 5-prime promoter region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8193350" 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>Using FISH, <a href="#34" class="mim-tip-reference" title="Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T. <strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong> Cell 73: 703-711, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500164">Takeda et al. (1993)</a> mapped the PIGA gene to chromosome Xp22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8500164" 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="#38" class="mim-tip-reference" title="Ware, R. E., Howard, T. A., Kamitani, T., Chang, H.-M., Yeh, E. T. H., Seldin, M. F. <strong>Chromosomal assignment of genes involved in glycosylphosphatidylinositol anchor biosynthesis: implications for the pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong> Blood 83: 3753-3757, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8204896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8204896</a>]" pmid="8204896">Ware et al. (1994)</a> used an interspecific cross to demonstrate that the Piga gene in the mouse is also located on the X chromosome. <a href="#13" class="mim-tip-reference" title="Kawagoe, K., Takeda, J., Endo, Y., Kinoshita, T. <strong>Molecular cloning of murine Pig-a, a gene for GPI-anchor biosynthesis, and demonstration of interspecies conservation of its structure, function, and genetic locus.</strong> Genomics 23: 566-574, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851884</a>] [<a href="https://doi.org/10.1006/geno.1994.1544" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7851884">Kawagoe et al. (1994)</a> also mapped the mouse Piga gene to the X chromosome in a region that shows homology of synteny to Xp22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7851884+8204896" 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="geneFamily" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFamilyFold" id="mimGeneFamilyToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFamilyToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Family</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFamilyFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>GPI is synthesized in the endoplasmic reticulum (ER) and transferred to the C termini of proteins with GPI attachment signal peptides. The common core structure of GPI consists of a molecule of phosphatidylinositol (PI) and a glycan core that contains glucosamine, 3 mannoses, and an ethanolamine phosphate. Biosynthesis of GPI anchors involves at least 10 reactions and more than 20 different proteins, including various members of the PIG gene family. The first step of GPI anchor biosynthesis, the transfer of N-acetylglucosamine (GlcNAc) from uridine 5-prime-diphospho-N-acetylglucosamide (UDP-GlcNAc) to PI to yield GlcNAc-PI, is catalyzed by a 7-subunit enzymatic complex that includes PIGA, PIGC (<a href="/entry/601730">601730</a>), PIGH (<a href="/entry/600154">600154</a>), PIGP (<a href="/entry/605938">605938</a>), PIGQ (<a href="/entry/605754">605754</a>), PIGY (<a href="/entry/610662">610662</a>), and DPM2 (<a href="/entry/603564">603564</a>). The intermediate steps of GPI anchor biosynthesis, which include de-N-acetylation of GlcNAc-PI to GlcN-PI, sequential addition of 3 mannoses from dolichol-phosphate-mannose and an ethanolamine phosphate from phosphatidylethanolamine, and modification of the core with side groups during or after synthesis, involve the PIGL (<a href="/entry/605947">605947</a>), PIGM (<a href="/entry/610273">610273</a>), PIGN (<a href="/entry/606097">606097</a>), PIGB (<a href="/entry/604122">604122</a>), PIGF (<a href="/entry/600153">600153</a>), PIGO (<a href="/entry/614730">614730</a>), PIGV (<a href="/entry/610274">610274</a>), PIGW (<a href="/entry/610275">610275</a>), and PIGX (<a href="/entry/610276">610276</a>) proteins, as well as DPM1 (<a href="/entry/603503">603503</a>), DPM3 (<a href="/entry/605951">605951</a>), and MPDU1 (<a href="/entry/604041">604041</a>). The last step in GPI anchor biosynthesis is attachment of the GPI anchor to the newly synthesized proprotein via a transamidase-like reaction that involves PIGK (<a href="/entry/605087">605087</a>), PIGS (<a href="/entry/610271">610271</a>), PIGT (<a href="/entry/610272">610272</a>), and PIGU (<a href="/entry/608528">608528</a>), as well as GPAA1 (<a href="/entry/603048">603048</a>). During this reaction, the C-terminal GPI attachment signal is released, and the GPI-anchored protein transits the secretory pathway to reach the plasma membrane, where it resides in lipid rafts (review by <a href="#5" class="mim-tip-reference" title="Brodsky, R. A. <strong>Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria.</strong> Blood Rev. 22: 65-74, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18063459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18063459</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18063459[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.blre.2007.10.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18063459">Brodsky, 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18063459" 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>Using human and mouse GPI anchor-deficient cell lines, <a href="#18" class="mim-tip-reference" title="Miyata, T., Takeda, J., Iida, Y., Yamada, N., Inoue, N., Takahashi, M., Maeda, K., Kitani, T., Kinoshita, T. <strong>The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.</strong> Science 259: 1318-1320, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7680492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7680492</a>] [<a href="https://doi.org/10.1126/science.7680492" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7680492">Miyata et al. (1993)</a> showed that PIGA takes part in the synthesis of GlcNAc-PI, the first intermediate in the biosynthetic pathway of GPI anchor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7680492" 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="Kawagoe, K., Takeda, J., Endo, Y., Kinoshita, T. <strong>Molecular cloning of murine Pig-a, a gene for GPI-anchor biosynthesis, and demonstration of interspecies conservation of its structure, function, and genetic locus.</strong> Genomics 23: 566-574, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851884</a>] [<a href="https://doi.org/10.1006/geno.1994.1544" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7851884">Kawagoe et al. (1994)</a> found that transfection of the mouse Piga cDNA complemented the defects of both a Piga-deficient murine cell line and a PIGA-deficient human cell line, demonstrating that functions of the mouse and human proteins are conserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Watanabe, R., Kinoshita, T., Masaki, R., Yamamoto, A., Takeda, J., Inoue, N. <strong>PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.</strong> J. Biol. Chem. 271: 26868-26875, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900170</a>] [<a href="https://doi.org/10.1074/jbc.271.43.26868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900170">Watanabe et al. (1996)</a> found that the PIGA and PIGH (<a href="/entry/600154">600154</a>) proteins form a protein complex and are subunits of the GPI GlcNAc transferase of the ER. They showed that PIGA is an ER transmembrane protein with a small luminal domain and a large cytoplasmic domain. The luminal domain contains information which targets the protein to the rough ER, while the cytoplasmic domain has homology to the bacterial GlcNAc transferase RfaK. <a href="#41" class="mim-tip-reference" title="Watanabe, R., Kinoshita, T., Masaki, R., Yamamoto, A., Takeda, J., Inoue, N. <strong>PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.</strong> J. Biol. Chem. 271: 26868-26875, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900170</a>] [<a href="https://doi.org/10.1074/jbc.271.43.26868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900170">Watanabe et al. (1996)</a> concluded that the first step of GPI anchor synthesis occurs on the cytoplasmic side of the ER membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900170" 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 immunoprecipitation experiments, <a href="#40" class="mim-tip-reference" title="Watanabe, R., Inoue, N., Westfall, B., Taron, C. H., Orlean, P., Takeda, J., Kinoshita, T. <strong>The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.</strong> EMBO J. 17: 877-885, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463366</a>] [<a href="https://doi.org/10.1093/emboj/17.4.877" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463366">Watanabe et al. (1998)</a> demonstrated that PIGQ (<a href="/entry/605754">605754</a>) associates specifically with PIGA, PIGC (<a href="/entry/601730">601730</a>), and PIGH and that all 4 proteins form a complex that has GPI-GlcNAc transferase (GPI-GnT) activity in vitro. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Paroxysmal Nocturnal Hemoglobinuria</em></strong></p><p>
|
|
Paroxysmal nocturnal hemoglobinuria (PNH; <a href="/entry/300818">300818</a>) is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the GPI anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. <a href="#36" class="mim-tip-reference" title="Ueda, E., Nishimura, J., Kitani, T., Nasu, K., Kageyama, T., Kim, Y. U., Takeda, J., Kinoshita, T. <strong>Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria.</strong> Int. Immun. 4: 1263-1271, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1282030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1282030</a>] [<a href="https://doi.org/10.1093/intimm/4.11.1263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1282030">Ueda et al. (1992)</a> established affected B-lymphocyte cell lines from 2 patients with PNH, and <a href="#33" class="mim-tip-reference" title="Takahashi, M., Takeda, J., Hirose, S., Hyman, R., Inoue, N., Miyata, T., Ueda, E., Kitani, T., Medof, M. E., Kinoshita, T. <strong>Deficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria.</strong> J. Exp. Med. 177: 517-521, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8426120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8426120</a>] [<a href="https://doi.org/10.1084/jem.177.2.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8426120">Takahashi et al. (1993)</a> demonstrated that the early step of GPI anchor biosynthesis was deficient in these cells. Complementation analysis by somatic cell hybridization with GPI-deficient mutant cell lines showed that these PNH cell lines belonged to complementation class A, which is known not to synthesize GlcNAc-PI. <a href="#34" class="mim-tip-reference" title="Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T. <strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong> Cell 73: 703-711, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500164">Takeda et al. (1993)</a> found that transfection of PIGA cDNA into affected B-lymphoblastoid cell lines restored their surface expression of GPI-anchored proteins. Further analysis demonstrated that the PIGA transcript was missing or present in very small amount in cell lines established from 1 patient, but that in a cell line established from another patient, deletion of thymine in a 5-prime splice site (<a href="#0001">311770.0001</a>) was associated with deletion of a PIGA exon located immediately 5-prime to the abnormal splice donor site. Since the PIGA gene maps to chromosome Xp22.1, and 1 of the patients studied was female, <a href="#34" class="mim-tip-reference" title="Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T. <strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong> Cell 73: 703-711, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500164">Takeda et al. (1993)</a> concluded that the mutant PIGA gene must reside on the active X chromosome. Affected cell lines established from 5 other patients with PNH were shown to belong to complementation group class A, indicating that the target gene is the same in most, if not all, patients with PNH. This can account for the behavior of the deficiency as a dominant in hemizygous males and in females with the mutant gene on the active X chromosome in a given lymphoblastoid cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8426120+1282030+8500164" 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="#27" class="mim-tip-reference" title="Rosse, W. F. <strong>Personal Communication.</strong> Durham, N. C. 6/3/1993."None>Rosse (1993)</a> indicated that all cases of PNH appear to have a defect in this gene, but the causative mutation has in all instances been unique. That many different mutations of PIGA may result in PNH may not be surprising since they arise as somatic mutations. <a href="#27" class="mim-tip-reference" title="Rosse, W. F. <strong>Personal Communication.</strong> Durham, N. C. 6/3/1993."None>Rosse (1993)</a> suggested that a germline mutation resulting in defects in this biosynthetic pathway would be lethal.</p><p><a href="#3" class="mim-tip-reference" title="Bessler, M., Mason, P. J., Hillmen, P., Miyata, T., Yamada, N., Takeda, J., Luzzatto, L., Kinoshita, T. <strong>Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene.</strong> EMBO J. 13: 110-117, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8306954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8306954</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06240.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8306954">Bessler et al. (1994)</a> reviewed the evidence that PNH is caused by somatic mutations in the PIGA gene. They demonstrated a somatic point mutation in 4 cases which, with the 2 mutations reported by <a href="#34" class="mim-tip-reference" title="Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T. <strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong> Cell 73: 703-711, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500164">Takeda et al. (1993)</a>, brought to 6 the number in which formal proof of the absence of normal PIGA gene product has been shown to produce the PNH phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8306954+8500164" 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 granulocytes from 3 of 15 patients with PNH, <a href="#19" class="mim-tip-reference" title="Miyata, T., Yamada, N., Iida, Y., Nishimura, J., Takeda, J., Kitani, T., Kinoshita, T. <strong>Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria.</strong> New Eng. J. Med. 330: 249-255, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8272086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8272086</a>] [<a href="https://doi.org/10.1056/NEJM199401273300404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8272086">Miyata et al. (1994)</a> found size abnormalities of PIGA transcripts with different patterns, and in 1 patient a very low level of the PIGA transcript was found. Although 11 patients had transcripts of normal size, transfection assay demonstrated that in each patient some of the transcripts were nonfunctional. The percentage of nonfunctional PIGA transcripts correlated with the percentage of affected granulocytes (P = less than 0.001). Sequence analysis demonstrated somatic mutations in 2 of the patients: deletion of a T (<a href="#0001">311770.0001</a>) and insertion of an A. The PIGA gene as the site of the defect in all patients with PNH is remarkable in light of the fact that PIGA is but 1 of at least 10 genes involved in GPI synthesis. The location of the gene on the X chromosome is probably responsible: somatic mutation in only one X chromosome is necessary to produce the mutation in a male cell or for that matter in a female cell if it occurs on the active X chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8272086" 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="#29" class="mim-tip-reference" title="Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L. <strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong> Hum. Genet. 97: 45-48, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8557259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8557259</a>] [<a href="https://doi.org/10.1007/BF00218831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8557259">Savoia et al. (1996)</a> found a novel mutation in the PIGA gene in each of 3 Italian patients with PNH. In each case, the mutation caused premature termination of translation of the PIGA protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8557259" 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="#23" class="mim-tip-reference" title="Nafa, K., Mason, P. J., Hillmen, P., Luzzatto, L., Bessler, M. <strong>Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type.</strong> Blood 86: 4650-4655, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541557</a>]" pmid="8541557">Nafa et al. (1995)</a> identified 15 different somatic mutations in 12 patients with PNH; 10 of them caused frameshifts. In each of 3 patients, 2 independent mutations were identified. Whereas G6PD mutations are virtually all single basepair changes that result in single amino acid replacements, most PIGA mutations are insertion-deletion mutations that cause frameshifts. The authors stated that the predominance of null mutations probably reflects the fact that the total absence of GPI-linked proteins provides a relative survival or growth advantage to the affected cells that is greater than that when the deficiency of GPI-linked proteins is only partial. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Nafa, K., Bessler, M., Castro-Malaspina, H., Jhanwar, S., Luzzatto, L. <strong>The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal hemoglobinuria includes large deletions and small duplications.</strong> Blood Cells Molec. Dis. 24: 370-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10087994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10087994</a>] [<a href="https://doi.org/10.1006/bcmd.1998.0203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10087994">Nafa et al. (1998)</a> described 28 previously unreported mutations. They confirmed that somatic mutations are spread throughout the entire coding region of the PIGA gene and that most frameshift mutations produce a nonfunctional PIGA protein. In addition, they found 1 total deletion of the PIGA gene, and 2 short nucleotide duplications (see <a href="#0010">311770.0010</a>). Although mutations are spread throughout the entire coding region, they observed more missense mutations in exon 2 than in other exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10087994" 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="Luzzatto, L., Bessler, M. <strong>The dual pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong> Curr. Opin. Hemat. 3: 101-110, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9372059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9372059</a>] [<a href="https://doi.org/10.1097/00062752-199603020-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9372059">Luzzatto and Bessler (1996)</a> and <a href="#15" class="mim-tip-reference" title="Luzzatto, L., Bessler, M., Rotoli, B. <strong>Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise?</strong> Cell 88: 1-4, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9019395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9019395</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81850-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9019395">Luzzatto et al. (1997)</a> reviewed the topic of PNH and gave a survey of the more than 100 somatic mutations in the PIGA gene that had been identified in patients with this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9019395+9372059" 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>Although many of the clinical manifestations (e.g., hemolytic anemia) of PNH can be explained by a deficiency of GPI-anchored complement regulatory proteins such as CD59 (<a href="/entry/107271">107271</a>) and CD55 (<a href="/entry/125240">125240</a>), it was unclear why PNH clonal cells dominate hematopoiesis and why they are prone to evolve into acute leukemia. <a href="#4" class="mim-tip-reference" title="Brodsky, R. A., Vala, M. S., Barber, J. P., Medof, M. E., Jones, R. J. <strong>Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria.</strong> Proc. Nat. Acad. Sci. 94: 8756-8760, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9238050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9238050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9238050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.16.8756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9238050">Brodsky et al. (1997)</a> found that PIGA mutations confer survival advantage by making cells relatively resistant to apoptotic death. When placed in serum-free medium, granulocytes and affected CD34(+) (<a href="/entry/142230">142230</a>) cells from PNH patients survive longer than their normal counterparts. PNH cells were also relatively resistant to apoptosis induced by ionizing irradiation. Replacement of the normal PIGA gene in PNH cell lines reversed the cellular resistance to apoptosis. <a href="#4" class="mim-tip-reference" title="Brodsky, R. A., Vala, M. S., Barber, J. P., Medof, M. E., Jones, R. J. <strong>Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria.</strong> Proc. Nat. Acad. Sci. 94: 8756-8760, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9238050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9238050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9238050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.16.8756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9238050">Brodsky et al. (1997)</a> speculated that apoptosis inhibition may be the principal mechanism by which PNH cells maintain a growth advantage over normal progenitors and could play a role in the propensity of this disease to transform into more aggressive hematologic disorders. The work also suggested that GPI anchors are important in regulating apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9238050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The clinical association between PNH and acquired aplastic anemia (AAA), and the observation that, as in AAA, PNH patients have decreased hematopoietic progenitors, may be taken to suggest a common pathogenetic process. There is strong evidence that AAA is an autoimmune disease and, as for AAA, bone marrow failure in PNH can be treated successfully with immunosuppression; thus, autoimmunity is likely to play a role in PNH as well. Specifically, it has been hypothesized that an autoimmune attack on normal stem cells targets a GPI-linked molecule and therefore preferentially spares the PNH stem cell, which thus has a growth or survival advantage (or both) in this abnormal environment. Using flow cytometric analysis of granulocytes, <a href="#1" class="mim-tip-reference" title="Araten, D. J., Nafa, K., Pakdeesuwan, K., Luzzatto, L. <strong>Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals.</strong> Proc. Nat. Acad. Sci. 96: 5209-5214, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10220445[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.9.5209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10220445">Araten et al. (1999)</a> identified cells that had the PNH phenotype (lack of expression of proteins linked to the membrane by a GPI anchor) at an average frequency of 22 per million in 9 normal individuals. These rare cells were collected by flow sorting, and exons 2 and 6 of the PIGA gene were amplified by nested PCR. The authors identified PIGA mutations in 6 cases. PNH red blood cells also were identified at a frequency of 8 per million. Thus, small clones with PIGA mutations existed commonly in normal individuals, showing clearly that PIGA gene mutations are not sufficient for the development of PNH. Because PIGA encodes an enzyme essential for the expression of a host of surface proteins, the PIGA gene provides a highly sensitive system for the study of somatic mutations in hematopoietic cells. In a note added in proof, <a href="#1" class="mim-tip-reference" title="Araten, D. J., Nafa, K., Pakdeesuwan, K., Luzzatto, L. <strong>Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals.</strong> Proc. Nat. Acad. Sci. 96: 5209-5214, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10220445[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.9.5209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10220445">Araten et al. (1999)</a> reported the finding of a tyr98-to-ter mutation (<a href="#0002">311770.0002</a>) in a 61-year-old man being phlebotomized for hemochromatosis. This was confirmed in samples taken 8 weeks apart. The same mutation had been reported in a patient with PNH (<a href="#29" class="mim-tip-reference" title="Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L. <strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong> Hum. Genet. 97: 45-48, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8557259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8557259</a>] [<a href="https://doi.org/10.1007/BF00218831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8557259">Savoia et al., 1996</a>). Thus, the same PIGA mutation that caused PNH in one person did not cause PNH in another person. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8557259+10220445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Hu, R., Mukhina, G. L., Piantadosi, S., Barber, J. P., Jones, R. J., Brodsky, R. A. <strong>PIG-A mutations in normal hematopoiesis.</strong> Blood 105: 3848-3854, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15687243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15687243</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15687243[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/10.1182/blood-2004-04-1472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15687243">Hu et al. (2005)</a> confirmed the finding that mutations of the PIGA gene are relatively common in normal hematopoiesis; however, they demonstrated that these mutations occur in differentiated progenitor cells rather than in hematopoietic stem cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15687243" 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>Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2</em></strong></p><p>
|
|
By exome sequencing of the X chromosome in a family with multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2; <a href="/entry/300868">300868</a>), <a href="#11" class="mim-tip-reference" title="Johnston, J. J., Gropman, A. L., Sapp, J. C., Teer, J. K., Martin, J. M., Liu, C. F., Yuan, X., Ye, Z., Cheng, L., Brodsky, R. A., Biesecker, L. G. <strong>The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria.</strong> Am. J. Hum. Genet. 90: 295-300, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22305531">Johnston et al. (2012)</a> identified a germline mutation in the PIGA gene (R412X; <a href="#0011">311770.0011</a>). Two affected boys carried the mutation, and 2 obligate female carriers were heterozygous for the mutation; both female carriers showed 100% skewed X inactivation. In vitro functional expression studies in PIGA-null cell lines showed that the R412X mutant protein retained some residual activity with partial restoration of GPI-anchored proteins, suggesting that it is not a null allele. The findings indicated that GPI anchors are important for normal development, particularly of the central nervous system. The patients had onset of seizures in the first weeks of life and died by 11 weeks of age. Neither patient had hemolytic anemia or clinical hemoglobinuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22305531" 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 male patient with MCAHS2 manifest as developmental and epileptic encephalopathy-20 (DEE20; <a href="/entry/300868">300868</a>), <a href="#2" class="mim-tip-reference" title="Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G. <strong>Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.</strong> Hum. Mutat. 35: 350-355, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357517</a>] [<a href="https://doi.org/10.1002/humu.22498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357517">Belet et al. (2014)</a> identified a hemizygous truncating mutation in the PIGA gene (<a href="#0012">311770.0012</a>). The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, was not found in 4 healthy male family members and was present in the unaffected mother of the proband, the unaffected grandmother, and a maternal aunt. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24357517" 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 5 boys from 4 unrelated Japanese families with MCAHS2 manifest as DEE20 with clinical diagnoses of Ohtahara or West syndrome, <a href="#12" class="mim-tip-reference" title="Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. <strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong> Neurology 82: 1587-1596, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706016</a>] [<a href="https://doi.org/10.1212/WNL.0000000000000389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706016">Kato et al. (2014)</a> identified a hemizygous mutation in the PIGA gene (see, e.g., <a href="#0011">311770.0011</a>; <a href="#0013">311770.0013</a>-<a href="#0015">311770.0015</a>). The mutations were found by whole-exome sequencing. In vitro functional expression studies showed a variable loss of PIGA activity, with a correlation between severity of phenotype and degree of residual enzymatic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706016" 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 boy with MCAHS2, <a href="#37" class="mim-tip-reference" title="van der Crabben, S. N., Harakalova, M., Brilstra, E. H., van Berkestijn, F. M. C., Hofstede, F. C., van Vught, A. J., Cuppen, E., Kloosterman, W., Ploos van Amstel, H. K., van Haaften, G., van Haelst, M. M. <strong>Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.</strong> Am. J. Med. Genet. 164A: 29-35, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24259184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24259184</a>] [<a href="https://doi.org/10.1002/ajmg.a.36184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24259184">van der Crabben et al. (2014)</a> identified a hemizygous mutation in the PIGA gene (<a href="#0017">311770.0017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24259184" 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>Neurodevelopmental Disorder with Epilepsy and Hemochromatosis</em></strong></p><p>
|
|
In 2 affected males from a large family with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; <a href="/entry/301072">301072</a>), <a href="#32" class="mim-tip-reference" title="Swoboda, K. J., Margraf, R. L., Carey, J. C., Zhou, H., Newcomb, T. M., Coonrod, E., Durtschi, J., Mallempati, K., Kumanovics, A., Katz, B. E., Voelkerding, K. V., Opitz, J. M. <strong>A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload.</strong> Am. J. Med. Genet. 164A: 17-28, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24259288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24259288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24259288[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.36189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24259288">Swoboda et al. (2014)</a> identified a hemizygous in-frame 3-bp deletion in the PIGA gene (leu110del; <a href="#0016">311770.0016</a>). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Flow cytometric analysis of the proband's granulocytes showed decreased cell surface levels of some GPI-anchored proteins, although CD59 (<a href="/entry/107271">107271</a>) expression on red blood cells was normal, suggesting that the mutant protein had some residual activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24259288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated patients with NEDEPH, <a href="#20" class="mim-tip-reference" title="Muckenthaler, L., Marques, O., Colucci, S., Kunz, J., Fabrowski, P., Bast, T., Altamura, S., Hochsmann, B., Schrezenmeier, H., Langlotz, M., Richter-Pechanska, P., Rausch, T., Hofmeister-Mielke, N., Gunkel, N., Hentze, M. W., Kulozik, A. E., Muckenthaler, M. U. <strong>Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.</strong> Blood 139: 1418-1422, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34875027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34875027</a>] [<a href="https://doi.org/10.1182/blood.2021013519" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34875027">Muckenthaler et al. (2022)</a> identified hemizygous missense mutations in the PIGA gene (R77Q, <a href="#0018">311770.0018</a>; L344P, <a href="#0019">311770.0019</a>; and S127L, <a href="#0020">311770.0020</a>). The mutations, which were found by exome sequencing or sequencing of a gene panel, were all inherited from an unaffected mother. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; <a href="/entry/608374">608374</a>), as well as caused decreased expression of hepcidin (<a href="/entry/606464">606464</a>) compared to controls. These findings indicated disruption of iron homeostasis. Transfection with wildtype PIGA rescued these defects, but expression of the L344P or R77Q mutations did not rescue hepcidin mRNA levels, consistent with a functional deficiency of PIGA. PIGA knockdown also reduced the levels of ceruloplasmin (CP), a GPI-anchored ferroxidase required for efficient cellular iron export. Reduced CP protein expression may aggravate iron overload and contribute to neurologic symptoms. The authors noted that the missense mutations had less deleterious effects than complete loss-of-function alleles, suggesting that the missense variants have residual function. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34875027" 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>Although a somatic PIGA mutation is responsible for deficiency of GPI-anchored proteins in PNH patients, no inherited form of GPI-anchor deficiency had been described. Piga gene inactivation in mouse embryonic stem (CES) cells followed by blastocyst injection is associated with a high rate of early embryonic lethality and low chimerism in surviving animals. Female mice heterozygous for a mutant Piga gene had never been obtained. To study the consequences of a nonfunctional Piga gene and to address the issue of a maternally inherited Piga mutation, <a href="#14" class="mim-tip-reference" title="Keller, P., Tremml, G., Rosti, V., Bessler, M. <strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong> Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10377440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.13.7479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10377440">Keller et al. (1999)</a> generated mice carrying a Piga mutation using Cre/loxP-controlled DNA recombination, as described by <a href="#28" class="mim-tip-reference" title="Sauer, B., Henderson, N. <strong>Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1.</strong> Proc. Nat. Acad. Sci. 85: 5166-5170, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2839833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2839833</a>] [<a href="https://doi.org/10.1073/pnas.85.14.5166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2839833">Sauer and Henderson (1988)</a>. High efficiency of Piga gene recombination was obtained by targeting Piga gene inactivation directly to the preimplantation female embryo. Because of X inactivation, newborn female mice were mosaic, with cells that expressed or lacked GPI-linked proteins. To assess the importance of PIGA in different organs, <a href="#14" class="mim-tip-reference" title="Keller, P., Tremml, G., Rosti, V., Bessler, M. <strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong> Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10377440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.13.7479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10377440">Keller et al. (1999)</a> examined the relative distribution of cells expressing or lacking GPI-linked proteins. Analysis of mosaic mice showed that in heart, lung, kidney, brain, and liver mainly wildtype Piga was active, suggesting that these tissues require GPI-linked proteins. The salient exceptions were spleen, thymus, and red blood cells, which had almost equal numbers of cells expressing the wildtype or the recombined allele, implying that GPI-linked proteins are not essential for the derivation of these tissues. PIGA(-) cells had no growth advantage, suggesting that other factors are needed for their clonal dominance in patients with paroxysmal nocturnal hemoglobinuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2839833+10377440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The fact that <a href="#14" class="mim-tip-reference" title="Keller, P., Tremml, G., Rosti, V., Bessler, M. <strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong> Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10377440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.13.7479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10377440">Keller et al. (1999)</a> were able to obtain female mice that carried in virtually all cells a mutated Piga gene raised the interesting issue of whether a heritable form of paroxysmal nocturnal hemoglobinuria exists. Because of X inactivation followed by cellular selection, female mice with high levels of Piga gene recombination were born alive. A biased male/female ratio of 1.5 suggested fetal wastage of highly recombined animals not rescued by the relative growth advantage of PIGA(+) cells. An inherited Piga mutation would be expected to follow a male-lethal, female-dominant inheritance pattern, with a varied phenotype in females depending on the proportion of cells expressing the mutant Piga gene. <a href="#14" class="mim-tip-reference" title="Keller, P., Tremml, G., Rosti, V., Bessler, M. <strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong> Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10377440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.13.7479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10377440">Keller et al. (1999)</a> found that a maternally inherited Piga mutation is embryonic lethal. In the embryo proper, X chromosome inactivation occurs at random. In contrast, in the trophoectoderm and in the primitive endoderm of the implanting embryo, the paternally derived X chromosome is preferentially inactivated. It is, therefore, conceivable that PIGA is essential in these tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10377440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The experiments of <a href="#14" class="mim-tip-reference" title="Keller, P., Tremml, G., Rosti, V., Bessler, M. <strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong> Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10377440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.13.7479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10377440">Keller et al. (1999)</a> did not exclude the possibility of sporadic mutations that, if occurring during early embryogenesis, may be found almost exclusively in females and thus mimic an X-linked dominant disease with prenatal lethality in males and a variable phenotype in females. In fact, <a href="#26" class="mim-tip-reference" title="Ogata, T., Wakui, K., Muroya, K., Ohashi, H., Matsuo, N., Brown, D. M., Ishii, T., Fukushima, Y. <strong>Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern.</strong> Hum. Genet. 103: 51-56, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9737776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9737776</a>] [<a href="https://doi.org/10.1007/s004390050782" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9737776">Ogata et al. (1998)</a> reported a female infant mosaic for an interstitial deletion within Xp22 spanning the critical region of the gene responsible for microphthalmia with linear skin defects (MLS; <a href="/entry/309801">309801</a>) and the PIGA gene, as determined by microsatellite analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10377440+9737776" 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>20 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/311770" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=311770[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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 1-BP DEL, T, IVSDS, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776723 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776723;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=rs587776723" 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=rs587776723" 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=RCV001799594" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799594" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799594</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In cells from a female patient (SS) with paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>), <a href="#34" class="mim-tip-reference" title="Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T. <strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong> Cell 73: 703-711, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500164">Takeda et al. (1993)</a> demonstrated a deletion of 207 bp from positions 982 to 1188 of the PIGA mRNA. The deletion was predicted to result in an aberrant protein with 69 amino acid residues deleted from the middle of the 484 amino acid protein. The same defect was found in a B-lymphocyte line and in the polymorphonuclear leukocytes, demonstrating that the affected cells, which were predominantly in peripheral blood, were derived from a clone of multipotential hematopoietic stem cells. <a href="#34" class="mim-tip-reference" title="Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T. <strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong> Cell 73: 703-711, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500164">Takeda et al. (1993)</a> further demonstrated that the 207-bp deletion corresponded to a single exon and that exon skipping had resulted from a 1-bp (T) deletion in the 5-prime splice site of the intron following the skipped exon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8500164" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, TYR98TER, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199422232 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422232;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=rs199422232" 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=rs199422232" 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=RCV001799595 OR RCV002460890" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799595, RCV002460890" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799595...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>), <a href="#29" class="mim-tip-reference" title="Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L. <strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong> Hum. Genet. 97: 45-48, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8557259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8557259</a>] [<a href="https://doi.org/10.1007/BF00218831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8557259">Savoia et al. (1996)</a> identified a C-to-A transversion at nucleotide 294 in exon 2 of the PIGA gene, resulting in a tyr98-to-ter mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8557259" 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 61-year-old man who was being phlebotomized for hemochromatosis, <a href="#1" class="mim-tip-reference" title="Araten, D. J., Nafa, K., Pakdeesuwan, K., Luzzatto, L. <strong>Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals.</strong> Proc. Nat. Acad. Sci. 96: 5209-5214, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10220445[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.9.5209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10220445">Araten et al. (1999)</a> identified the same mutation. Thus, the same PIGA mutation that caused PNH in one person did not cause PNH in another person. This was taken as strong support for 'dual pathogenesis of PNH' (<a href="#16" class="mim-tip-reference" title="Luzzatto, L., Bessler, M. <strong>The dual pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong> Curr. Opin. Hemat. 3: 101-110, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9372059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9372059</a>] [<a href="https://doi.org/10.1097/00062752-199603020-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9372059">Luzzatto and Bessler, 1996</a>). Although a PIGA gene mutation may be necessary for the development of PNH, it is not sufficient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9372059+10220445" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 1-BP INS, 460A, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776724 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776724;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=rs587776724" 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=rs587776724" 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=RCV001799596" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799596" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799596</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with paroxysmal nocturnal hemoglobinuria, <a href="#29" class="mim-tip-reference" title="Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L. <strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong> Hum. Genet. 97: 45-48, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8557259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8557259</a>] [<a href="https://doi.org/10.1007/BF00218831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8557259">Savoia et al. (1996)</a> demonstrated an insertion of A at nucleotide 460 (460insA) of the PIGA gene, resulting in a new reading frame that was terminated by a stop codon 8 codons downstream. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8557259" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 1-BP DEL, 1114C, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776725 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776725;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=rs587776725" 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=rs587776725" 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=RCV001799597" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799597" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799597</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>), <a href="#29" class="mim-tip-reference" title="Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L. <strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong> Hum. Genet. 97: 45-48, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8557259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8557259</a>] [<a href="https://doi.org/10.1007/BF00218831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8557259">Savoia et al. (1996)</a> demonstrated a deletion of 1 of the 2 cytosines at nucleotides 1114-1115 (1114delC) causing a frameshift that resulted in a termination signal 9 codons downstream. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8557259" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, GLN55TER, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199422233 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422233;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=rs199422233" 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=rs199422233" 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=RCV001799598" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799598" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799598</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 4 patients developing paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>) after treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin, <a href="#24" class="mim-tip-reference" title="Nagarajan, S., Brodsky, R. A., Young, N. S., Medof, M. E. <strong>Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia.</strong> Blood 86: 4656-4661, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541558</a>]" pmid="8541558">Nagarajan et al. (1995)</a> observed a C-to-T transition of nucleotide 163 of the PIGA gene, changing codon 55 from gln to TGA (stop). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541558" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 2-BP INS, 334GT, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776726 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776726;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=rs587776726" 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=rs587776726" 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=RCV001799599" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799599" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799599</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>), <a href="#39" class="mim-tip-reference" title="Ware, R. E., Rosse, W. F., Howard, T. A. <strong>Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria.</strong> Blood 83: 2418-2422, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8167330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8167330</a>]" pmid="8167330">Ware et al. (1994)</a> identified a 2-bp (GT) insertion at nucleotide position 334 of the PIGA gene leading to a premature termination codon (TGA) at nucleotide position 370. The erythrocytes and granulocytes in this patient were exclusively type III cells, indicating a complete deficiency in surface expression of glycosylphosphatidylinositol-linked proteins and causing complete loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8167330" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 1-BP DEL, 516C, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776727 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776727;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=rs587776727" 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=rs587776727" 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=RCV001799600" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799600" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799600</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>), <a href="#39" class="mim-tip-reference" title="Ware, R. E., Rosse, W. F., Howard, T. A. <strong>Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria.</strong> Blood 83: 2418-2422, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8167330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8167330</a>]" pmid="8167330">Ware et al. (1994)</a> identified a 1-bp deletion (C) at nucleotide position 516 of the PIGA gene leading to a premature termination codon (TAA) at nucleotide position 598. The erythrocytes and granulocytes in this patient were exclusively type III cells, indicating a complete deficiency in surface expression of glycosylphosphatidylinositol-linked proteins and causing complete loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8167330" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 2-BP DEL, 1408CT, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776728 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776728;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=rs587776728" 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=rs587776728" 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=RCV001799601" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799601" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799601</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>), <a href="#39" class="mim-tip-reference" title="Ware, R. E., Rosse, W. F., Howard, T. A. <strong>Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria.</strong> Blood 83: 2418-2422, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8167330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8167330</a>]" pmid="8167330">Ware et al. (1994)</a> identified a 2-bp (CT) deletion at nucleotide position 1408 of the PIGA gene leading to a premature termination codon (TGA) at nucleotide position 1438. The erythrocytes and granulocytes in this patient were exclusively type III cells, indicating a complete deficiency in surface expression of glycosylphosphatidylinositol-linked protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8167330" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, IVS5DS, G-A, +1, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2147717286 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2147717286;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=rs2147717286" 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=rs2147717286" 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=RCV001799602" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799602" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799602</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Maugard, C., Margueritte, G., Tuffery, S., Rabesandratana, H., Demaille, J., Claustres, M. <strong>Recurrent PIG-A mutation (IVS5+1G-A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test.</strong> Brit. J. Haemat. 98: 21-24, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9233558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9233558</a>] [<a href="https://doi.org/10.1046/j.1365-2141.1997.1742988.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9233558">Maugard et al. (1997)</a> noted that only a few cases of paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>) had been described in children and adolescents. They reported the case of a male diagnosed with PNH at 12 years of age during follow-up of aplastic anemia, which had initially been diagnosed at the age of 8.5 years and was treated with cyclosporin and growth factors. Using the protein truncation test to scan for truncating mutations in PIGA mRNA reverse-transcribed and amplified from blood mononuclear cells, <a href="#17" class="mim-tip-reference" title="Maugard, C., Margueritte, G., Tuffery, S., Rabesandratana, H., Demaille, J., Claustres, M. <strong>Recurrent PIG-A mutation (IVS5+1G-A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test.</strong> Brit. J. Haemat. 98: 21-24, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9233558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9233558</a>] [<a href="https://doi.org/10.1046/j.1365-2141.1997.1742988.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9233558">Maugard et al. (1997)</a> found a donor splice site mutation, IVS5+1G-A, which had previously been described in a Japanese and a Thai adult with PNH. The recurrence in 3 unrelated patients from distinct ethnic origins suggested that this site, although not located in a CpG-type hypermutable sequence, may represent a mutation hotspot. The authors pointed out that scanning PIGA mRNA for mutations rather than genomic DNA is advantageous because it avoids the amplification of sequences from the PIGA pseudogene at 12q21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9233558" 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 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 2-BP INS/32-BP DUP, SOMATIC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786200912 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200912;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=rs786200912" 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=rs786200912" 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=RCV001799603" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001799603" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001799603</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="Nafa, K., Bessler, M., Deeg, H. J., Luzzatto, L. <strong>New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria.</strong> Blood 92: 3422-3427, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9787183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9787183</a>]" pmid="9787183">Nafa et al. (1998)</a> reported a detailed longitudinal study of the first patient to be treated (in 1973) for paroxysmal nocturnal hemoglobinuria (<a href="/entry/300818">300818</a>) with syngeneic bone marrow transplantation. The patient, a male, was 19 years old at the time of BMT. Bone marrow was derived from a monozygotic twin. The patient subsequently relapsed with PNH in 1983, and still had PNH to the time of report. Analysis of the PIGA gene in the 1990s showed an insertion-duplication in exon 6, causing a frameshift. The mutation was the insertion of 2 adenines at position 1355, followed by a duplication of the preceding 32 nucleotides (1324-1355). This introduced a frameshift at codon 452 and led to a truncated PIGA protein of only 462 amino acids. PCR amplification of the PIGA exon 6 from bone marrow slides obtained before BMT showed that this duplication was not present; instead, <a href="#22" class="mim-tip-reference" title="Nafa, K., Bessler, M., Deeg, H. J., Luzzatto, L. <strong>New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria.</strong> Blood 92: 3422-3427, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9787183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9787183</a>]" pmid="9787183">Nafa et al. (1998)</a> found several single basepair substitutions in exons 2 and 6. Thus, relapse of PNH in this patient was not due to persistence of the original clones; rather, it was associated with the emergence of a new clone. These findings support the notion that the bone marrow environment may create selective conditions favoring the expansion of PNH clones. The changes found in the archival material included a 211A-G transition in exon 2, causing a thr71-to-ala substitution, and a 251C-T transition in exon 2, causing a thr84-to-ile substitution. The former change was present in 50% of clones and the latter change was present in 28% of those clones as a second mutation, suggesting that the latter mutation arose in a cell belonging to the clone that had the former mutation. A third mutation in exon 2, a 16G-T transversion causing a gly6-to-ter substitution, was present in 14% of clones. The finding of multiple mutational clones, as was the case after relapse, is not unusual in PNH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9787183" 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 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, ARG412TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906726 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906726;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=rs387906726" 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=rs387906726" 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=RCV000022881 OR RCV001007979" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022881, RCV001007979" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022881...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing of the X chromosome in a family with multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2; <a href="/entry/300868">300868</a>), <a href="#11" class="mim-tip-reference" title="Johnston, J. J., Gropman, A. L., Sapp, J. C., Teer, J. K., Martin, J. M., Liu, C. F., Yuan, X., Ye, Z., Cheng, L., Brodsky, R. A., Biesecker, L. G. <strong>The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria.</strong> Am. J. Hum. Genet. 90: 295-300, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22305531">Johnston et al. (2012)</a> identified a 1234C-T transition in the last exon of the PIGA gene, resulting in an arg412-to-ter (R412X) substitution and truncation of the final C-terminal 109 amino acids. The mutation was not found in multiple large control sets. In vitro functional expression studies in PIGA-null cell lines showed that the R412X mutant protein retained some residual activity with partial restoration of GPI-anchored proteins, suggesting that it is not a null allele. The findings indicated that GPI anchors are important for normal development, particularly of the central nervous system. The patients had onset of seizures associated with burst-suppression pattern on EEG in the first weeks of life; both died by 11 weeks of age. The findings were consistent with a developmental and epileptic encephalopathy (DEE). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22305531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. <strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong> Neurology 82: 1587-1596, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706016</a>] [<a href="https://doi.org/10.1212/WNL.0000000000000389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706016">Kato et al. (2014)</a> identified the R412X mutation in a 6-year-old Japanese boy with MCAHS2 manifest as early infantile epileptic encephalopathy with a clinical diagnosis of Ohtahara syndrome. He had severe disability, myoclonus, and quadriplegia. In vitro functional expression studies showed that the mutant protein could partially restore GPI-anchored protein expression in PIGA-null cells, suggesting that a small amount of full-length protein was generated by read-through of the stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Fauth, C., Steindl, K., Toutain, A., Farrell, S., Witsch-Baumgartner, M., Karall, D., Joset, P., Bohm, S., Baumer, A., Maier, O., Zschocke, J., Weksberg, R., Marshall, C. R., Rauch, A. <strong>A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2.</strong> Am. J. Med. Genet. 170A: 392-402, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26545172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26545172</a>] [<a href="https://doi.org/10.1002/ajmg.a.37452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26545172">Fauth et al. (2016)</a> identified a hemizygous R412X mutation (c.1234C-T, NM_002641.3) in 4 affected males from 3 unrelated families with MCAHS2. One of the families had been reported by <a href="#35" class="mim-tip-reference" title="Terespolsky, D., Farrell, S. A., Siegel-Bartelt, J., Weksberg, R. <strong>Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis.</strong> Am. J. Med. Genet. 59: 329-333, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8599356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8599356</a>] [<a href="https://doi.org/10.1002/ajmg.1320590310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8599356">Terespolsky et al. (1995)</a> and originally classified as having Simpson-Golabi-Behmel syndrome type 2 (SGBS2; <a href="/entry/300209">300209</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26545172+8599356" 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 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 1-BP DUP, 76T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777397 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777397;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=rs587777397" 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=rs587777397" 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=RCV000119284" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119284" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119284</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 24-year-old man with MCAHS2 (<a href="/entry/300868">300868</a>) manifest as developmental and epileptic encephalopathy, <a href="#2" class="mim-tip-reference" title="Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G. <strong>Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.</strong> Hum. Mutat. 35: 350-355, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357517</a>] [<a href="https://doi.org/10.1002/humu.22498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357517">Belet et al. (2014)</a> identified a hemizygous 1-bp duplication (c.76dupT) in exon 2 of the PIGA gene, resulting in a frameshift and premature termination (Tyr26LeufsTer3). The family had previously been reported by <a href="#6" class="mim-tip-reference" title="Claes, S., Devriendt, K., Lagae, L., Ceulemans, B., Dom, L., Casaer, P., Raeymaekers, P., Cassiman, J. J., Fryns, J. P. <strong>The X-linked infantile spasms syndrome (MIM 308350) maps to Xp11.4-Xpter in two pedigrees.</strong> Ann. Neurol. 42: 360-364, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9307258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9307258</a>] [<a href="https://doi.org/10.1002/ana.410420313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9307258">Claes et al. (1997)</a> as having West syndrome. The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in the 1000 Genomes Project, dbSNP (build 135), or Exome Variant Server databases, or in an in-house control database. Patient cells showed normal PIGA expression due to the production of a normal shorter PIGA isoform that lacks exon 2. Patient cells showed normal expression of CD59 (<a href="/entry/107271">107271</a>), and complementation assays showed that this shorter PIGA cDNA was able to partially rescue the surface expression of CD59 in a PIGA-null cell line. <a href="#2" class="mim-tip-reference" title="Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G. <strong>Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.</strong> Hum. Mutat. 35: 350-355, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357517</a>] [<a href="https://doi.org/10.1002/humu.22498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357517">Belet et al. (2014)</a> suggested that the mutation was a hypomorph that could rescue lethality in males, but could not compensate for the MCAHS2 phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9307258+24357517" 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 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, ARG77LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777398 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777398;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=rs587777398" 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=rs587777398" 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=RCV000119285" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119285" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119285</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Japanese brothers with MCAHS2 (<a href="/entry/300868">300868</a>) manifest as developmental and epileptic encephalopathy, <a href="#12" class="mim-tip-reference" title="Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. <strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong> Neurology 82: 1587-1596, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706016</a>] [<a href="https://doi.org/10.1212/WNL.0000000000000389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706016">Kato et al. (2014)</a> identified a hemizygous c.230G-T transversion in exon 2 of the PIGA gene, resulting in an arg77-to-leu (R77L) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was not found in the Exome Variant Server database or in 573 in-house control exomes. In vitro functional expression studies showed that the mutant protein could partially restore GPI-anchored protein expression in PIGA-null cells. The patients had a slightly less severe phenotype than other patients with PIGA mutations (see, e.g., <a href="#0011">311770.0011</a> and <a href="#0014">311770.0014</a>), which correlated with more residual PIGA enzymatic activity for the R77L protein. The patients had onset of seizures at 7 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, ILE206PHE
|
|
</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> rs201119959 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201119959;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/rs201119959?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=rs201119959" 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=rs201119959" 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=RCV000119286" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119286" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119286</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese boy with MCAHS2 (<a href="/entry/300868">300868</a>) manifest as West syndrome, <a href="#12" class="mim-tip-reference" title="Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. <strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong> Neurology 82: 1587-1596, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706016</a>] [<a href="https://doi.org/10.1212/WNL.0000000000000389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706016">Kato et al. (2014)</a> identified a hemizygous c.6161A-T transversion in exon 2 of the PIGA gene, resulting in an ile206-to-phe (I206F) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was not found in the Exome Variant Server database or in 573 in-house control exomes. In vitro functional expression studies showed that the mutant protein could partially restore GPI-anchored protein expression in PIGA-null cells. The patient had onset of seizures at 6 months of age; the phenotype was consistent with a developmental and epileptic encephalopathy (DEE). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706016" 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="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, ARG119TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777396 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777396;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=rs587777396" 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=rs587777396" 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=RCV000119283 OR RCV000443275 OR RCV004820831" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119283, RCV000443275, RCV004820831" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119283...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-month-old Japanese boy with MCAHS2 (<a href="/entry/300868">300868</a>) manifest as West syndrome, <a href="#12" class="mim-tip-reference" title="Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. <strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong> Neurology 82: 1587-1596, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706016</a>] [<a href="https://doi.org/10.1212/WNL.0000000000000389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706016">Kato et al. (2014)</a> identified a hemizygous c.355C-T transition in exon 2 of the PIGA gene, resulting in an arg119-to-trp (R119W) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was not found in the Exome Variant Server database or in 573 in-house control exomes. The patient had onset of seizures at 3 months of age; the phenotype was consistent with a developmental and epileptic encephalopathy (DEE). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706016" 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="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, 3-BP DEL, 328CTT
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777399 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777399;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=rs587777399" 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=rs587777399" 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=RCV000478249 OR RCV002221150 OR RCV002281561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000478249, RCV002221150, RCV002281561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000478249...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected males from a family with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; <a href="/entry/301072">301072</a>), <a href="#32" class="mim-tip-reference" title="Swoboda, K. J., Margraf, R. L., Carey, J. C., Zhou, H., Newcomb, T. M., Coonrod, E., Durtschi, J., Mallempati, K., Kumanovics, A., Katz, B. E., Voelkerding, K. V., Opitz, J. M. <strong>A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload.</strong> Am. J. Med. Genet. 164A: 17-28, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24259288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24259288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24259288[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.36189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24259288">Swoboda et al. (2014)</a> identified a hemizygous in-frame 3-bp deletion (c.328_330delCTT, NM_020473.3) in the PIGA gene, resulting in the deletion of a conserved residue (leu110del). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not present in the 1000 Genomes Project or Exome Variant Server databases. Flow cytometric analysis of the proband's granulocytes showed decreased cell surface levels of some GPI-anchored proteins, although CD59 (<a href="/entry/107271">107271</a>) expression on red blood cells was normal, suggesting that the mutant protein had some residual activity. In addition to neurologic features, the patients had cutaneous abnormalities and evidence of systemic iron overload. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24259288" 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="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, PRO93LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777400 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777400;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=rs587777400" 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=rs587777400" 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=RCV000119288" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119288" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119288</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with MCAHS2 (<a href="/entry/300868">300868</a>), <a href="#37" class="mim-tip-reference" title="van der Crabben, S. N., Harakalova, M., Brilstra, E. H., van Berkestijn, F. M. C., Hofstede, F. C., van Vught, A. J., Cuppen, E., Kloosterman, W., Ploos van Amstel, H. K., van Haaften, G., van Haelst, M. M. <strong>Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.</strong> Am. J. Med. Genet. 164A: 29-35, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24259184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24259184</a>] [<a href="https://doi.org/10.1002/ajmg.a.36184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24259184">van der Crabben et al. (2014)</a> identified a hemizygous c.278C-T transition in the PIGA gene, resulting in a pro93-to-leu (P93L) substitution in a highly conserved GPI-anchored biosynthesis domain region. The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP (build 137) or Exome Variant Server databases, or in 100 in-house control exomes. The mother and maternal grandmother were unaffected carriers, and the mother showed 100% skewing of the X-chromosome harboring the mutation. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24259184" 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="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, ARG77GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777398 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777398;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=rs587777398" 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=rs587777398" 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=RCV000999330 OR RCV002221259" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000999330, RCV002221259" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000999330...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 13-year-old boy (patient 1) with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; <a href="/entry/301072">301072</a>), <a href="#20" class="mim-tip-reference" title="Muckenthaler, L., Marques, O., Colucci, S., Kunz, J., Fabrowski, P., Bast, T., Altamura, S., Hochsmann, B., Schrezenmeier, H., Langlotz, M., Richter-Pechanska, P., Rausch, T., Hofmeister-Mielke, N., Gunkel, N., Hentze, M. W., Kulozik, A. E., Muckenthaler, M. U. <strong>Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.</strong> Blood 139: 1418-1422, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34875027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34875027</a>] [<a href="https://doi.org/10.1182/blood.2021013519" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34875027">Muckenthaler et al. (2022)</a> identified a hemizygous c.230G-A transition in the PIGA gene, resulting in an arg77-to-gln (R77Q) substitution. The mutation, which was found by exome sequencing, was inherited from the unaffected mother. In vitro functional expression studies showed that the mutation resulted in a partial loss of PIGA function with decreased levels of certain GPI-anchored proteins involved in iron homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34875027" 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="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, LEU344PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs761007687 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs761007687;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=rs761007687" 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=rs761007687" 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=RCV000512946 OR RCV002221237" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000512946, RCV002221237" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000512946...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy (patient 2) with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; <a href="/entry/301072">301072</a>), <a href="#20" class="mim-tip-reference" title="Muckenthaler, L., Marques, O., Colucci, S., Kunz, J., Fabrowski, P., Bast, T., Altamura, S., Hochsmann, B., Schrezenmeier, H., Langlotz, M., Richter-Pechanska, P., Rausch, T., Hofmeister-Mielke, N., Gunkel, N., Hentze, M. W., Kulozik, A. E., Muckenthaler, M. U. <strong>Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.</strong> Blood 139: 1418-1422, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34875027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34875027</a>] [<a href="https://doi.org/10.1182/blood.2021013519" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34875027">Muckenthaler et al. (2022)</a> identified a hemizygous c.1031T-C transition in the PIGA gene, resulting in a leu344-to-pro (L344P) substitution. The mutation, which was found by next-generation panel sequencing, was inherited from the unaffected mother. In vitro functional expression studies showed that the mutation resulted in a partial loss of PIGA function with decreased levels of certain GPI-anchored proteins involved in iron homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34875027" 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="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
PIGA, SER127LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2147723740 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2147723740;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=rs2147723740" 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=rs2147723740" 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=RCV002221186" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002221186" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002221186</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old boy (patient 3) with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; <a href="/entry/301072">301072</a>), <a href="#20" class="mim-tip-reference" title="Muckenthaler, L., Marques, O., Colucci, S., Kunz, J., Fabrowski, P., Bast, T., Altamura, S., Hochsmann, B., Schrezenmeier, H., Langlotz, M., Richter-Pechanska, P., Rausch, T., Hofmeister-Mielke, N., Gunkel, N., Hentze, M. W., Kulozik, A. E., Muckenthaler, M. U. <strong>Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.</strong> Blood 139: 1418-1422, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34875027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34875027</a>] [<a href="https://doi.org/10.1182/blood.2021013519" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34875027">Muckenthaler et al. (2022)</a> identified a hemizygous c.380C-T transition in the PIGA gene, resulting in a ser127-to-leu (S127L) substitution. The mutation, which was found by next-generation panel sequencing, was inherited from the unaffected mother. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be a hypomorphic allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34875027" 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="Araten1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Araten, D. J., Nafa, K., Pakdeesuwan, K., Luzzatto, L.
|
|
<strong>Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 5209-5214, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10220445[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=10220445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.9.5209" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Belet2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G.
|
|
<strong>Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.</strong>
|
|
Hum. Mutat. 35: 350-355, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24357517" 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.22498" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bessler1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bessler, M., Mason, P. J., Hillmen, P., Miyata, T., Yamada, N., Takeda, J., Luzzatto, L., Kinoshita, T.
|
|
<strong>Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene.</strong>
|
|
EMBO J. 13: 110-117, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8306954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8306954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8306954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06240.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Brodsky1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brodsky, R. A., Vala, M. S., Barber, J. P., Medof, M. E., Jones, R. J.
|
|
<strong>Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 8756-8760, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9238050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9238050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9238050[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=9238050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.94.16.8756" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Brodsky2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brodsky, R. A.
|
|
<strong>Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood Rev. 22: 65-74, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18063459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18063459</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18063459[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=18063459" 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.blre.2007.10.002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Claes1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Claes, S., Devriendt, K., Lagae, L., Ceulemans, B., Dom, L., Casaer, P., Raeymaekers, P., Cassiman, J. J., Fryns, J. P.
|
|
<strong>The X-linked infantile spasms syndrome (MIM 308350) maps to Xp11.4-Xpter in two pedigrees.</strong>
|
|
Ann. Neurol. 42: 360-364, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9307258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9307258</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9307258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.410420313" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Fauth2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fauth, C., Steindl, K., Toutain, A., Farrell, S., Witsch-Baumgartner, M., Karall, D., Joset, P., Bohm, S., Baumer, A., Maier, O., Zschocke, J., Weksberg, R., Marshall, C. R., Rauch, A.
|
|
<strong>A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2.</strong>
|
|
Am. J. Med. Genet. 170A: 392-402, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26545172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26545172</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26545172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.37452" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Hirose1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hirose, S., Mohney, R. P., Mutka, S. C., Ravi, L., Singleton, D. R., Perry, G., Tartakoff, A. M., Medof, M. E.
|
|
<strong>Derivation and characterization of glycoinositol-phospholipid anchor-defective human K562 cell clones.</strong>
|
|
J. Biol. Chem. 267: 5272-5278, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1371997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1371997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1371997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Hu2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hu, R., Mukhina, G. L., Piantadosi, S., Barber, J. P., Jones, R. J., Brodsky, R. A.
|
|
<strong>PIG-A mutations in normal hematopoiesis.</strong>
|
|
Blood 105: 3848-3854, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15687243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15687243</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15687243[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=15687243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2004-04-1472" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Iida1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iida, Y., Takeda, J., Miyata, T., Inoue, N., Nishimura, J., Kitani, T., Maeda, K., Kinoshita, T.
|
|
<strong>Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 83: 3126-3131, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8193350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8193350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8193350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Johnston2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnston, J. J., Gropman, A. L., Sapp, J. C., Teer, J. K., Martin, J. M., Liu, C. F., Yuan, X., Ye, Z., Cheng, L., Brodsky, R. A., Biesecker, L. G.
|
|
<strong>The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Am. J. Hum. Genet. 90: 295-300, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305531[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=22305531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2011.11.031" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kato2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N.
|
|
<strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong>
|
|
Neurology 82: 1587-1596, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706016</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0000000000000389" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Kawagoe1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kawagoe, K., Takeda, J., Endo, Y., Kinoshita, T.
|
|
<strong>Molecular cloning of murine Pig-a, a gene for GPI-anchor biosynthesis, and demonstration of interspecies conservation of its structure, function, and genetic locus.</strong>
|
|
Genomics 23: 566-574, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851884</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851884" 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.1994.1544" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Keller1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keller, P., Tremml, G., Rosti, V., Bessler, M.
|
|
<strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10377440[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=10377440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.13.7479" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Luzzatto1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Luzzatto, L., Bessler, M., Rotoli, B.
|
|
<strong>Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise?</strong>
|
|
Cell 88: 1-4, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9019395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9019395</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9019395" 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)81850-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Luzzatto1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Luzzatto, L., Bessler, M.
|
|
<strong>The dual pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Curr. Opin. Hemat. 3: 101-110, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9372059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9372059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9372059" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00062752-199603020-00001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Maugard1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maugard, C., Margueritte, G., Tuffery, S., Rabesandratana, H., Demaille, J., Claustres, M.
|
|
<strong>Recurrent PIG-A mutation (IVS5+1G-A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test.</strong>
|
|
Brit. J. Haemat. 98: 21-24, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9233558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9233558</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9233558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.1997.1742988.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Miyata1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miyata, T., Takeda, J., Iida, Y., Yamada, N., Inoue, N., Takahashi, M., Maeda, K., Kitani, T., Kinoshita, T.
|
|
<strong>The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.</strong>
|
|
Science 259: 1318-1320, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7680492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7680492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7680492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.7680492" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Miyata1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miyata, T., Yamada, N., Iida, Y., Nishimura, J., Takeda, J., Kitani, T., Kinoshita, T.
|
|
<strong>Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
New Eng. J. Med. 330: 249-255, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8272086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8272086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8272086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199401273300404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Muckenthaler2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muckenthaler, L., Marques, O., Colucci, S., Kunz, J., Fabrowski, P., Bast, T., Altamura, S., Hochsmann, B., Schrezenmeier, H., Langlotz, M., Richter-Pechanska, P., Rausch, T., Hofmeister-Mielke, N., Gunkel, N., Hentze, M. W., Kulozik, A. E., Muckenthaler, M. U.
|
|
<strong>Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.</strong>
|
|
Blood 139: 1418-1422, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34875027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34875027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34875027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood.2021013519" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Nafa1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nafa, K., Bessler, M., Castro-Malaspina, H., Jhanwar, S., Luzzatto, L.
|
|
<strong>The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal hemoglobinuria includes large deletions and small duplications.</strong>
|
|
Blood Cells Molec. Dis. 24: 370-384, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10087994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10087994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10087994" 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/bcmd.1998.0203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Nafa1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nafa, K., Bessler, M., Deeg, H. J., Luzzatto, L.
|
|
<strong>New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 92: 3422-3427, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9787183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9787183</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9787183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Nafa1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nafa, K., Mason, P. J., Hillmen, P., Luzzatto, L., Bessler, M.
|
|
<strong>Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type.</strong>
|
|
Blood 86: 4650-4655, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541557</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Nagarajan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nagarajan, S., Brodsky, R. A., Young, N. S., Medof, M. E.
|
|
<strong>Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia.</strong>
|
|
Blood 86: 4656-4661, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541558</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Nagarajan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nagarajan, S., Brown, C. J., Medof, M. E.
|
|
<strong>Identification of a PIG-A related processed gene on chromosome 12.</strong>
|
|
Hum. Genet. 95: 691-697, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7654280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7654280</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7654280" 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/BF00209489" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Ogata1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ogata, T., Wakui, K., Muroya, K., Ohashi, H., Matsuo, N., Brown, D. M., Ishii, T., Fukushima, Y.
|
|
<strong>Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern.</strong>
|
|
Hum. Genet. 103: 51-56, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9737776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9737776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9737776" 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/s004390050782" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Rosse1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosse, W. F.
|
|
<strong>Personal Communication.</strong>
|
|
Durham, N. C. 6/3/1993.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Sauer1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sauer, B., Henderson, N.
|
|
<strong>Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 5166-5170, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2839833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2839833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2839833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.85.14.5166" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Savoia1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L.
|
|
<strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong>
|
|
Hum. Genet. 97: 45-48, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8557259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8557259</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8557259" 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/BF00218831" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Stevens1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stevens, V. L., Raetz, C. R. H.
|
|
<strong>Defective glycosyl phosphatidylinositol biosynthesis in extracts of three thy-1 negative lymphoma cell mutants.</strong>
|
|
J. Biol. Chem. 266: 10039-10042, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1828068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1828068</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1828068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Sugiyama1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sugiyama, E., DeGasperi, R., Urakaze, M., Chang, H.-M., Thomas, L. J., Hyman, R., Warren, C. D., Yeh, E. T. H.
|
|
<strong>Identification of defects in glycosylphosphatidylinositol anchor biosynthesis in the thy-1 expression mutants.</strong>
|
|
J. Biol. Chem. 266: 12119-12122, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1829456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1829456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1829456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Swoboda2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Swoboda, K. J., Margraf, R. L., Carey, J. C., Zhou, H., Newcomb, T. M., Coonrod, E., Durtschi, J., Mallempati, K., Kumanovics, A., Katz, B. E., Voelkerding, K. V., Opitz, J. M.
|
|
<strong>A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload.</strong>
|
|
Am. J. Med. Genet. 164A: 17-28, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24259288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24259288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24259288[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=24259288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.36189" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Takahashi1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takahashi, M., Takeda, J., Hirose, S., Hyman, R., Inoue, N., Miyata, T., Ueda, E., Kitani, T., Medof, M. E., Kinoshita, T.
|
|
<strong>Deficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
J. Exp. Med. 177: 517-521, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8426120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8426120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8426120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.177.2.517" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Takeda1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T.
|
|
<strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Cell 73: 703-711, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8500164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(93)90250-t" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Terespolsky1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Terespolsky, D., Farrell, S. A., Siegel-Bartelt, J., Weksberg, R.
|
|
<strong>Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis.</strong>
|
|
Am. J. Med. Genet. 59: 329-333, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8599356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8599356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8599356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320590310" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Ueda1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ueda, E., Nishimura, J., Kitani, T., Nasu, K., Kageyama, T., Kim, Y. U., Takeda, J., Kinoshita, T.
|
|
<strong>Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Int. Immun. 4: 1263-1271, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1282030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1282030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1282030" 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/intimm/4.11.1263" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="van der Crabben2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van der Crabben, S. N., Harakalova, M., Brilstra, E. H., van Berkestijn, F. M. C., Hofstede, F. C., van Vught, A. J., Cuppen, E., Kloosterman, W., Ploos van Amstel, H. K., van Haaften, G., van Haelst, M. M.
|
|
<strong>Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.</strong>
|
|
Am. J. Med. Genet. 164A: 29-35, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24259184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24259184</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24259184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.36184" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Ware1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ware, R. E., Howard, T. A., Kamitani, T., Chang, H.-M., Yeh, E. T. H., Seldin, M. F.
|
|
<strong>Chromosomal assignment of genes involved in glycosylphosphatidylinositol anchor biosynthesis: implications for the pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 83: 3753-3757, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8204896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8204896</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8204896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Ware1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ware, R. E., Rosse, W. F., Howard, T. A.
|
|
<strong>Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 83: 2418-2422, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8167330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8167330</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8167330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Watanabe1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Watanabe, R., Inoue, N., Westfall, B., Taron, C. H., Orlean, P., Takeda, J., Kinoshita, T.
|
|
<strong>The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.</strong>
|
|
EMBO J. 17: 877-885, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463366</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463366" 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/emboj/17.4.877" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Watanabe1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Watanabe, R., Kinoshita, T., Masaki, R., Yamamoto, A., Takeda, J., Inoue, N.
|
|
<strong>PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 271: 26868-26875, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.271.43.26868" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Yu1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu, J., Nagarajan, S., Ueda, E., Knez, J. J., Petersen, R. B., Medof, M. E.
|
|
<strong>Characterization of alternatively spliced PIG-A transcripts in normal and paroxysmal nocturnal hemoglobinuria cells.</strong>
|
|
Braz. J. Med. Biol. Res. 27: 195-201, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081230</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8081230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 03/23/2022
|
|
</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">
|
|
Matthew B. Gross - updated : 01/10/2018<br>Cassandra L. Kniffin - updated : 3/29/2016<br>Cassandra L. Kniffin - updated : 5/21/2014<br>Cassandra L. Kniffin - updated : 2/28/2012<br>Matthew B. Gross - updated : 7/1/2010<br>Victor A. McKusick - updated : 8/31/2005<br>Victor A. McKusick - updated : 6/20/2005<br>Victor A. McKusick - updated : 2/24/2004<br>Victor A. McKusick - updated : 1/21/2003<br>Victor A. McKusick - updated : 2/22/2002<br>Dawn Watkins-Chow - updated : 3/22/2001<br>Victor A. McKusick - updated : 2/18/2000<br>Victor A. McKusick - updated : 1/21/2000<br>Victor A. McKusick - updated : 7/19/1999<br>Victor A. McKusick - updated : 2/27/1999<br>Victor A. McKusick - updated : 2/27/1999<br>Victor A. McKusick - updated : 9/16/1997<br>Victor A. McKusick - updated : 9/12/1997<br>Jennifer P. Macke - updated : 5/27/1997<br>Victor A. McKusick - edited : 3/7/1997<br>Victor A. McKusick - updated : 2/11/1997<br>Cynthia K. Ewing - updated : 10/14/1996<br>Stylianos E. Antonarakis - updated : 7/8/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/8/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 03/25/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 04/07/2022<br>alopez : 04/05/2022<br>ckniffin : 03/23/2022<br>alopez : 10/13/2020<br>ckniffin : 10/08/2020<br>mgross : 01/10/2018<br>mgross : 04/25/2016<br>carol : 3/31/2016<br>alopez : 3/30/2016<br>ckniffin : 3/29/2016<br>carol : 3/9/2015<br>alopez : 5/22/2014<br>mcolton : 5/22/2014<br>ckniffin : 5/21/2014<br>carol : 3/2/2012<br>ckniffin : 2/28/2012<br>carol : 7/2/2010<br>mgross : 7/1/2010<br>mgross : 7/1/2010<br>mgross : 7/1/2010<br>terry : 7/26/2006<br>wwang : 8/31/2005<br>terry : 8/31/2005<br>terry : 8/3/2005<br>alopez : 6/22/2005<br>terry : 6/20/2005<br>ckniffin : 7/15/2004<br>carol : 3/17/2004<br>tkritzer : 2/26/2004<br>terry : 2/24/2004<br>cwells : 1/24/2003<br>cwells : 1/24/2003<br>tkritzer : 1/21/2003<br>tkritzer : 1/21/2003<br>cwells : 3/13/2002<br>cwells : 3/11/2002<br>terry : 2/22/2002<br>carol : 3/22/2001<br>carol : 3/22/2001<br>mgross : 3/16/2000<br>terry : 2/18/2000<br>carol : 2/2/2000<br>terry : 1/21/2000<br>mcapotos : 12/8/1999<br>alopez : 7/28/1999<br>terry : 7/19/1999<br>terry : 3/1/1999<br>carol : 2/27/1999<br>carol : 2/27/1999<br>dkim : 9/11/1998<br>alopez : 5/21/1998<br>carol : 3/10/1998<br>jenny : 9/19/1997<br>terry : 9/16/1997<br>terry : 9/12/1997<br>alopez : 7/24/1997<br>alopez : 7/24/1997<br>alopez : 6/3/1997<br>alopez : 4/4/1997<br>alopez : 4/3/1997<br>mark : 3/7/1997<br>terry : 2/11/1997<br>terry : 2/4/1997<br>mark : 1/3/1997<br>terry : 12/16/1996<br>jenny : 12/12/1996<br>terry : 12/9/1996<br>jamie : 10/23/1996<br>jamie : 10/16/1996<br>jamie : 10/14/1996<br>mark : 7/8/1996<br>mark : 3/11/1996<br>terry : 3/4/1996<br>mark : 1/14/1996<br>carol : 12/13/1994<br>terry : 10/19/1994<br>jason : 7/12/1994<br>warfield : 4/20/1994<br>mimadm : 2/28/1994<br>carol : 8/31/1993
|
|
</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> 311770
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS A PROTEIN; PIGA
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS A PROTEIN, PSEUDOGENE 1, INCLUDED; PIGAP1, INCLUDED; PIGAP, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: PIGA</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 1963002, 774151000;
|
|
|
|
|
|
<strong>ICD10CM:</strong> D59.5;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: Xp22.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:15,319,451-15,335,554 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
Xp22.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Multiple congenital anomalies-hypotonia-seizures syndrome 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300868
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Neurodevelopmental disorder with epilepsy and hemochromatosis
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
301072
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Paroxysmal nocturnal hemoglobinuria, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300818
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</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>Glycosylphosphatidylinositol (GPI) is a glycolipid that attaches dozens of different proteins to the cell surface. PIGA is 1 of several proteins required for the first step of GPI anchor biosynthesis (review by Brodsky, 2008). </p><p>For further information on the PIG gene family and GPI biosynthesis, see GENE FAMILY.</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>Some of the genes involved in GPI biosynthesis are represented by different complementation classes of GPI anchor-deficient mutant cells derived from human and rodent cell lines (Stevens and Raetz, 1991; Sugiyama et al., 1991; Hirose et al., 1992). By expression cloning using a GPI anchor-deficient human B-lymphoblastoid cell line belonging to complementation class A, Miyata et al. (1993) cloned PIGA. The predicted 484-amino acid PIGA protein has a single transmembrane domain. </p><p>Kawagoe et al. (1994) reported that the deduced amino acid sequence of the mouse Piga protein is 88% identical to that of the human protein. Database analysis demonstrated that a yeast gene, Spt14, is homologous and that these genes are members of a glycosyltransferase gene family. </p><p>The PIGA gene encodes 4 isoforms, 2 coding and 2 noncoding. Belet et al. (2014) found that the major isoform encodes a 484-residue protein that starts in and includes exon 2 and was expressed in all tested human tissues. The second coding isoform starts in exon 1, but skips exon 2 and produces a truncated protein of 250 residues. </p><p><strong><em>PIGA Pseudogene 1</em></strong></p><p>
|
|
In the course of analyses of PIGA genetic alterations in patients with paroxysmal nocturnal hemoglobinuria (PNH; 300818) (see MOLECULAR GENETICS), Yu et al. (1994) amplified PIGA transcripts expressed in affected lymphocytes by RT-PCR and unexpectedly found a product differing from the authentic PIGA product by 126 nucleotide exchanges and 5 deletions in the coding region. Nagarajan et al. (1995) showed that mRNA with this sequence was coexpressed with PIGA mRNA in a wide range of cell types. Mapping of genomic DNA from human/rodent hybrids showed that the sequence derived from an intronless processed gene (PIGAP) on chromosome 12. Duplicated processed genes had been described for a number of X-linked genes, including pyruvate dehydrogenase (300502), the adenine nucleotide translocase genes (300150 and 300151), and phosphoglycerate kinase (311800). The identification of a stop codon at position 243 in the mRNA sequence of the PIGAP gene on chromosome 12 indicates that if this mRNA is translated, its protein product is probably not functional. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Iida et al. (1994) reported that the PIGA gene is at least 17 kb long and has 6 exons. They sequenced the exon-intron boundaries and described the characteristics of the 5-prime promoter region. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using FISH, Takeda et al. (1993) mapped the PIGA gene to chromosome Xp22.1. </p><p>Ware et al. (1994) used an interspecific cross to demonstrate that the Piga gene in the mouse is also located on the X chromosome. Kawagoe et al. (1994) also mapped the mouse Piga gene to the X chromosome in a region that shows homology of synteny to Xp22.1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Family</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>GPI is synthesized in the endoplasmic reticulum (ER) and transferred to the C termini of proteins with GPI attachment signal peptides. The common core structure of GPI consists of a molecule of phosphatidylinositol (PI) and a glycan core that contains glucosamine, 3 mannoses, and an ethanolamine phosphate. Biosynthesis of GPI anchors involves at least 10 reactions and more than 20 different proteins, including various members of the PIG gene family. The first step of GPI anchor biosynthesis, the transfer of N-acetylglucosamine (GlcNAc) from uridine 5-prime-diphospho-N-acetylglucosamide (UDP-GlcNAc) to PI to yield GlcNAc-PI, is catalyzed by a 7-subunit enzymatic complex that includes PIGA, PIGC (601730), PIGH (600154), PIGP (605938), PIGQ (605754), PIGY (610662), and DPM2 (603564). The intermediate steps of GPI anchor biosynthesis, which include de-N-acetylation of GlcNAc-PI to GlcN-PI, sequential addition of 3 mannoses from dolichol-phosphate-mannose and an ethanolamine phosphate from phosphatidylethanolamine, and modification of the core with side groups during or after synthesis, involve the PIGL (605947), PIGM (610273), PIGN (606097), PIGB (604122), PIGF (600153), PIGO (614730), PIGV (610274), PIGW (610275), and PIGX (610276) proteins, as well as DPM1 (603503), DPM3 (605951), and MPDU1 (604041). The last step in GPI anchor biosynthesis is attachment of the GPI anchor to the newly synthesized proprotein via a transamidase-like reaction that involves PIGK (605087), PIGS (610271), PIGT (610272), and PIGU (608528), as well as GPAA1 (603048). During this reaction, the C-terminal GPI attachment signal is released, and the GPI-anchored protein transits the secretory pathway to reach the plasma membrane, where it resides in lipid rafts (review by Brodsky, 2008). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using human and mouse GPI anchor-deficient cell lines, Miyata et al. (1993) showed that PIGA takes part in the synthesis of GlcNAc-PI, the first intermediate in the biosynthetic pathway of GPI anchor. </p><p>Kawagoe et al. (1994) found that transfection of the mouse Piga cDNA complemented the defects of both a Piga-deficient murine cell line and a PIGA-deficient human cell line, demonstrating that functions of the mouse and human proteins are conserved. </p><p>Watanabe et al. (1996) found that the PIGA and PIGH (600154) proteins form a protein complex and are subunits of the GPI GlcNAc transferase of the ER. They showed that PIGA is an ER transmembrane protein with a small luminal domain and a large cytoplasmic domain. The luminal domain contains information which targets the protein to the rough ER, while the cytoplasmic domain has homology to the bacterial GlcNAc transferase RfaK. Watanabe et al. (1996) concluded that the first step of GPI anchor synthesis occurs on the cytoplasmic side of the ER membrane. </p><p>Using immunoprecipitation experiments, Watanabe et al. (1998) demonstrated that PIGQ (605754) associates specifically with PIGA, PIGC (601730), and PIGH and that all 4 proteins form a complex that has GPI-GlcNAc transferase (GPI-GnT) activity in vitro. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Paroxysmal Nocturnal Hemoglobinuria</em></strong></p><p>
|
|
Paroxysmal nocturnal hemoglobinuria (PNH; 300818) is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the GPI anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Ueda et al. (1992) established affected B-lymphocyte cell lines from 2 patients with PNH, and Takahashi et al. (1993) demonstrated that the early step of GPI anchor biosynthesis was deficient in these cells. Complementation analysis by somatic cell hybridization with GPI-deficient mutant cell lines showed that these PNH cell lines belonged to complementation class A, which is known not to synthesize GlcNAc-PI. Takeda et al. (1993) found that transfection of PIGA cDNA into affected B-lymphoblastoid cell lines restored their surface expression of GPI-anchored proteins. Further analysis demonstrated that the PIGA transcript was missing or present in very small amount in cell lines established from 1 patient, but that in a cell line established from another patient, deletion of thymine in a 5-prime splice site (311770.0001) was associated with deletion of a PIGA exon located immediately 5-prime to the abnormal splice donor site. Since the PIGA gene maps to chromosome Xp22.1, and 1 of the patients studied was female, Takeda et al. (1993) concluded that the mutant PIGA gene must reside on the active X chromosome. Affected cell lines established from 5 other patients with PNH were shown to belong to complementation group class A, indicating that the target gene is the same in most, if not all, patients with PNH. This can account for the behavior of the deficiency as a dominant in hemizygous males and in females with the mutant gene on the active X chromosome in a given lymphoblastoid cell line. </p><p>Rosse (1993) indicated that all cases of PNH appear to have a defect in this gene, but the causative mutation has in all instances been unique. That many different mutations of PIGA may result in PNH may not be surprising since they arise as somatic mutations. Rosse (1993) suggested that a germline mutation resulting in defects in this biosynthetic pathway would be lethal.</p><p>Bessler et al. (1994) reviewed the evidence that PNH is caused by somatic mutations in the PIGA gene. They demonstrated a somatic point mutation in 4 cases which, with the 2 mutations reported by Takeda et al. (1993), brought to 6 the number in which formal proof of the absence of normal PIGA gene product has been shown to produce the PNH phenotype. </p><p>In granulocytes from 3 of 15 patients with PNH, Miyata et al. (1994) found size abnormalities of PIGA transcripts with different patterns, and in 1 patient a very low level of the PIGA transcript was found. Although 11 patients had transcripts of normal size, transfection assay demonstrated that in each patient some of the transcripts were nonfunctional. The percentage of nonfunctional PIGA transcripts correlated with the percentage of affected granulocytes (P = less than 0.001). Sequence analysis demonstrated somatic mutations in 2 of the patients: deletion of a T (311770.0001) and insertion of an A. The PIGA gene as the site of the defect in all patients with PNH is remarkable in light of the fact that PIGA is but 1 of at least 10 genes involved in GPI synthesis. The location of the gene on the X chromosome is probably responsible: somatic mutation in only one X chromosome is necessary to produce the mutation in a male cell or for that matter in a female cell if it occurs on the active X chromosome. </p><p>Savoia et al. (1996) found a novel mutation in the PIGA gene in each of 3 Italian patients with PNH. In each case, the mutation caused premature termination of translation of the PIGA protein. </p><p>Nafa et al. (1995) identified 15 different somatic mutations in 12 patients with PNH; 10 of them caused frameshifts. In each of 3 patients, 2 independent mutations were identified. Whereas G6PD mutations are virtually all single basepair changes that result in single amino acid replacements, most PIGA mutations are insertion-deletion mutations that cause frameshifts. The authors stated that the predominance of null mutations probably reflects the fact that the total absence of GPI-linked proteins provides a relative survival or growth advantage to the affected cells that is greater than that when the deficiency of GPI-linked proteins is only partial. </p><p>Nafa et al. (1998) described 28 previously unreported mutations. They confirmed that somatic mutations are spread throughout the entire coding region of the PIGA gene and that most frameshift mutations produce a nonfunctional PIGA protein. In addition, they found 1 total deletion of the PIGA gene, and 2 short nucleotide duplications (see 311770.0010). Although mutations are spread throughout the entire coding region, they observed more missense mutations in exon 2 than in other exons. </p><p>Luzzatto and Bessler (1996) and Luzzatto et al. (1997) reviewed the topic of PNH and gave a survey of the more than 100 somatic mutations in the PIGA gene that had been identified in patients with this disorder. </p><p>Although many of the clinical manifestations (e.g., hemolytic anemia) of PNH can be explained by a deficiency of GPI-anchored complement regulatory proteins such as CD59 (107271) and CD55 (125240), it was unclear why PNH clonal cells dominate hematopoiesis and why they are prone to evolve into acute leukemia. Brodsky et al. (1997) found that PIGA mutations confer survival advantage by making cells relatively resistant to apoptotic death. When placed in serum-free medium, granulocytes and affected CD34(+) (142230) cells from PNH patients survive longer than their normal counterparts. PNH cells were also relatively resistant to apoptosis induced by ionizing irradiation. Replacement of the normal PIGA gene in PNH cell lines reversed the cellular resistance to apoptosis. Brodsky et al. (1997) speculated that apoptosis inhibition may be the principal mechanism by which PNH cells maintain a growth advantage over normal progenitors and could play a role in the propensity of this disease to transform into more aggressive hematologic disorders. The work also suggested that GPI anchors are important in regulating apoptosis. </p><p>The clinical association between PNH and acquired aplastic anemia (AAA), and the observation that, as in AAA, PNH patients have decreased hematopoietic progenitors, may be taken to suggest a common pathogenetic process. There is strong evidence that AAA is an autoimmune disease and, as for AAA, bone marrow failure in PNH can be treated successfully with immunosuppression; thus, autoimmunity is likely to play a role in PNH as well. Specifically, it has been hypothesized that an autoimmune attack on normal stem cells targets a GPI-linked molecule and therefore preferentially spares the PNH stem cell, which thus has a growth or survival advantage (or both) in this abnormal environment. Using flow cytometric analysis of granulocytes, Araten et al. (1999) identified cells that had the PNH phenotype (lack of expression of proteins linked to the membrane by a GPI anchor) at an average frequency of 22 per million in 9 normal individuals. These rare cells were collected by flow sorting, and exons 2 and 6 of the PIGA gene were amplified by nested PCR. The authors identified PIGA mutations in 6 cases. PNH red blood cells also were identified at a frequency of 8 per million. Thus, small clones with PIGA mutations existed commonly in normal individuals, showing clearly that PIGA gene mutations are not sufficient for the development of PNH. Because PIGA encodes an enzyme essential for the expression of a host of surface proteins, the PIGA gene provides a highly sensitive system for the study of somatic mutations in hematopoietic cells. In a note added in proof, Araten et al. (1999) reported the finding of a tyr98-to-ter mutation (311770.0002) in a 61-year-old man being phlebotomized for hemochromatosis. This was confirmed in samples taken 8 weeks apart. The same mutation had been reported in a patient with PNH (Savoia et al., 1996). Thus, the same PIGA mutation that caused PNH in one person did not cause PNH in another person. </p><p>Hu et al. (2005) confirmed the finding that mutations of the PIGA gene are relatively common in normal hematopoiesis; however, they demonstrated that these mutations occur in differentiated progenitor cells rather than in hematopoietic stem cells. </p><p><strong><em>Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2</em></strong></p><p>
|
|
By exome sequencing of the X chromosome in a family with multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2; 300868), Johnston et al. (2012) identified a germline mutation in the PIGA gene (R412X; 311770.0011). Two affected boys carried the mutation, and 2 obligate female carriers were heterozygous for the mutation; both female carriers showed 100% skewed X inactivation. In vitro functional expression studies in PIGA-null cell lines showed that the R412X mutant protein retained some residual activity with partial restoration of GPI-anchored proteins, suggesting that it is not a null allele. The findings indicated that GPI anchors are important for normal development, particularly of the central nervous system. The patients had onset of seizures in the first weeks of life and died by 11 weeks of age. Neither patient had hemolytic anemia or clinical hemoglobinuria. </p><p>In a male patient with MCAHS2 manifest as developmental and epileptic encephalopathy-20 (DEE20; 300868), Belet et al. (2014) identified a hemizygous truncating mutation in the PIGA gene (311770.0012). The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, was not found in 4 healthy male family members and was present in the unaffected mother of the proband, the unaffected grandmother, and a maternal aunt. </p><p>In 5 boys from 4 unrelated Japanese families with MCAHS2 manifest as DEE20 with clinical diagnoses of Ohtahara or West syndrome, Kato et al. (2014) identified a hemizygous mutation in the PIGA gene (see, e.g., 311770.0011; 311770.0013-311770.0015). The mutations were found by whole-exome sequencing. In vitro functional expression studies showed a variable loss of PIGA activity, with a correlation between severity of phenotype and degree of residual enzymatic activity. </p><p>In a boy with MCAHS2, van der Crabben et al. (2014) identified a hemizygous mutation in the PIGA gene (311770.0017). </p><p><strong><em>Neurodevelopmental Disorder with Epilepsy and Hemochromatosis</em></strong></p><p>
|
|
In 2 affected males from a large family with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; 301072), Swoboda et al. (2014) identified a hemizygous in-frame 3-bp deletion in the PIGA gene (leu110del; 311770.0016). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Flow cytometric analysis of the proband's granulocytes showed decreased cell surface levels of some GPI-anchored proteins, although CD59 (107271) expression on red blood cells was normal, suggesting that the mutant protein had some residual activity. </p><p>In 3 unrelated patients with NEDEPH, Muckenthaler et al. (2022) identified hemizygous missense mutations in the PIGA gene (R77Q, 311770.0018; L344P, 311770.0019; and S127L, 311770.0020). The mutations, which were found by exome sequencing or sequencing of a gene panel, were all inherited from an unaffected mother. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These findings indicated disruption of iron homeostasis. Transfection with wildtype PIGA rescued these defects, but expression of the L344P or R77Q mutations did not rescue hepcidin mRNA levels, consistent with a functional deficiency of PIGA. PIGA knockdown also reduced the levels of ceruloplasmin (CP), a GPI-anchored ferroxidase required for efficient cellular iron export. Reduced CP protein expression may aggravate iron overload and contribute to neurologic symptoms. The authors noted that the missense mutations had less deleterious effects than complete loss-of-function alleles, suggesting that the missense variants have residual function. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Although a somatic PIGA mutation is responsible for deficiency of GPI-anchored proteins in PNH patients, no inherited form of GPI-anchor deficiency had been described. Piga gene inactivation in mouse embryonic stem (CES) cells followed by blastocyst injection is associated with a high rate of early embryonic lethality and low chimerism in surviving animals. Female mice heterozygous for a mutant Piga gene had never been obtained. To study the consequences of a nonfunctional Piga gene and to address the issue of a maternally inherited Piga mutation, Keller et al. (1999) generated mice carrying a Piga mutation using Cre/loxP-controlled DNA recombination, as described by Sauer and Henderson (1988). High efficiency of Piga gene recombination was obtained by targeting Piga gene inactivation directly to the preimplantation female embryo. Because of X inactivation, newborn female mice were mosaic, with cells that expressed or lacked GPI-linked proteins. To assess the importance of PIGA in different organs, Keller et al. (1999) examined the relative distribution of cells expressing or lacking GPI-linked proteins. Analysis of mosaic mice showed that in heart, lung, kidney, brain, and liver mainly wildtype Piga was active, suggesting that these tissues require GPI-linked proteins. The salient exceptions were spleen, thymus, and red blood cells, which had almost equal numbers of cells expressing the wildtype or the recombined allele, implying that GPI-linked proteins are not essential for the derivation of these tissues. PIGA(-) cells had no growth advantage, suggesting that other factors are needed for their clonal dominance in patients with paroxysmal nocturnal hemoglobinuria. </p><p>The fact that Keller et al. (1999) were able to obtain female mice that carried in virtually all cells a mutated Piga gene raised the interesting issue of whether a heritable form of paroxysmal nocturnal hemoglobinuria exists. Because of X inactivation followed by cellular selection, female mice with high levels of Piga gene recombination were born alive. A biased male/female ratio of 1.5 suggested fetal wastage of highly recombined animals not rescued by the relative growth advantage of PIGA(+) cells. An inherited Piga mutation would be expected to follow a male-lethal, female-dominant inheritance pattern, with a varied phenotype in females depending on the proportion of cells expressing the mutant Piga gene. Keller et al. (1999) found that a maternally inherited Piga mutation is embryonic lethal. In the embryo proper, X chromosome inactivation occurs at random. In contrast, in the trophoectoderm and in the primitive endoderm of the implanting embryo, the paternally derived X chromosome is preferentially inactivated. It is, therefore, conceivable that PIGA is essential in these tissues. </p><p>The experiments of Keller et al. (1999) did not exclude the possibility of sporadic mutations that, if occurring during early embryogenesis, may be found almost exclusively in females and thus mimic an X-linked dominant disease with prenatal lethality in males and a variable phenotype in females. In fact, Ogata et al. (1998) reported a female infant mosaic for an interstitial deletion within Xp22 spanning the critical region of the gene responsible for microphthalmia with linear skin defects (MLS; 309801) and the PIGA gene, as determined by microsatellite analysis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>20 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 1-BP DEL, T, IVSDS, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776723,
|
|
|
|
|
|
|
|
ClinVar: RCV001799594
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In cells from a female patient (SS) with paroxysmal nocturnal hemoglobinuria (300818), Takeda et al. (1993) demonstrated a deletion of 207 bp from positions 982 to 1188 of the PIGA mRNA. The deletion was predicted to result in an aberrant protein with 69 amino acid residues deleted from the middle of the 484 amino acid protein. The same defect was found in a B-lymphocyte line and in the polymorphonuclear leukocytes, demonstrating that the affected cells, which were predominantly in peripheral blood, were derived from a clone of multipotential hematopoietic stem cells. Takeda et al. (1993) further demonstrated that the 207-bp deletion corresponded to a single exon and that exon skipping had resulted from a 1-bp (T) deletion in the 5-prime splice site of the intron following the skipped exon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, TYR98TER, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422232,
|
|
|
|
|
|
|
|
ClinVar: RCV001799595, RCV002460890
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with paroxysmal nocturnal hemoglobinuria (300818), Savoia et al. (1996) identified a C-to-A transversion at nucleotide 294 in exon 2 of the PIGA gene, resulting in a tyr98-to-ter mutation. </p><p>In a 61-year-old man who was being phlebotomized for hemochromatosis, Araten et al. (1999) identified the same mutation. Thus, the same PIGA mutation that caused PNH in one person did not cause PNH in another person. This was taken as strong support for 'dual pathogenesis of PNH' (Luzzatto and Bessler, 1996). Although a PIGA gene mutation may be necessary for the development of PNH, it is not sufficient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 1-BP INS, 460A, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776724,
|
|
|
|
|
|
|
|
ClinVar: RCV001799596
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with paroxysmal nocturnal hemoglobinuria, Savoia et al. (1996) demonstrated an insertion of A at nucleotide 460 (460insA) of the PIGA gene, resulting in a new reading frame that was terminated by a stop codon 8 codons downstream. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 1-BP DEL, 1114C, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776725,
|
|
|
|
|
|
|
|
ClinVar: RCV001799597
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient with paroxysmal nocturnal hemoglobinuria (300818), Savoia et al. (1996) demonstrated a deletion of 1 of the 2 cytosines at nucleotides 1114-1115 (1114delC) causing a frameshift that resulted in a termination signal 9 codons downstream. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, GLN55TER, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422233,
|
|
|
|
|
|
|
|
ClinVar: RCV001799598
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 4 patients developing paroxysmal nocturnal hemoglobinuria (300818) after treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin, Nagarajan et al. (1995) observed a C-to-T transition of nucleotide 163 of the PIGA gene, changing codon 55 from gln to TGA (stop). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 2-BP INS, 334GT, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776726,
|
|
|
|
|
|
|
|
ClinVar: RCV001799599
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with paroxysmal nocturnal hemoglobinuria (300818), Ware et al. (1994) identified a 2-bp (GT) insertion at nucleotide position 334 of the PIGA gene leading to a premature termination codon (TGA) at nucleotide position 370. The erythrocytes and granulocytes in this patient were exclusively type III cells, indicating a complete deficiency in surface expression of glycosylphosphatidylinositol-linked proteins and causing complete loss of function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 1-BP DEL, 516C, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776727,
|
|
|
|
|
|
|
|
ClinVar: RCV001799600
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with paroxysmal nocturnal hemoglobinuria (300818), Ware et al. (1994) identified a 1-bp deletion (C) at nucleotide position 516 of the PIGA gene leading to a premature termination codon (TAA) at nucleotide position 598. The erythrocytes and granulocytes in this patient were exclusively type III cells, indicating a complete deficiency in surface expression of glycosylphosphatidylinositol-linked proteins and causing complete loss of function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 2-BP DEL, 1408CT, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776728,
|
|
|
|
|
|
|
|
ClinVar: RCV001799601
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with paroxysmal nocturnal hemoglobinuria (300818), Ware et al. (1994) identified a 2-bp (CT) deletion at nucleotide position 1408 of the PIGA gene leading to a premature termination codon (TGA) at nucleotide position 1438. The erythrocytes and granulocytes in this patient were exclusively type III cells, indicating a complete deficiency in surface expression of glycosylphosphatidylinositol-linked protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, IVS5DS, G-A, +1, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2147717286,
|
|
|
|
|
|
|
|
ClinVar: RCV001799602
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Maugard et al. (1997) noted that only a few cases of paroxysmal nocturnal hemoglobinuria (300818) had been described in children and adolescents. They reported the case of a male diagnosed with PNH at 12 years of age during follow-up of aplastic anemia, which had initially been diagnosed at the age of 8.5 years and was treated with cyclosporin and growth factors. Using the protein truncation test to scan for truncating mutations in PIGA mRNA reverse-transcribed and amplified from blood mononuclear cells, Maugard et al. (1997) found a donor splice site mutation, IVS5+1G-A, which had previously been described in a Japanese and a Thai adult with PNH. The recurrence in 3 unrelated patients from distinct ethnic origins suggested that this site, although not located in a CpG-type hypermutable sequence, may represent a mutation hotspot. The authors pointed out that scanning PIGA mRNA for mutations rather than genomic DNA is advantageous because it avoids the amplification of sequences from the PIGA pseudogene at 12q21. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 2-BP INS/32-BP DUP, SOMATIC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786200912,
|
|
|
|
|
|
|
|
ClinVar: RCV001799603
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Nafa et al. (1998) reported a detailed longitudinal study of the first patient to be treated (in 1973) for paroxysmal nocturnal hemoglobinuria (300818) with syngeneic bone marrow transplantation. The patient, a male, was 19 years old at the time of BMT. Bone marrow was derived from a monozygotic twin. The patient subsequently relapsed with PNH in 1983, and still had PNH to the time of report. Analysis of the PIGA gene in the 1990s showed an insertion-duplication in exon 6, causing a frameshift. The mutation was the insertion of 2 adenines at position 1355, followed by a duplication of the preceding 32 nucleotides (1324-1355). This introduced a frameshift at codon 452 and led to a truncated PIGA protein of only 462 amino acids. PCR amplification of the PIGA exon 6 from bone marrow slides obtained before BMT showed that this duplication was not present; instead, Nafa et al. (1998) found several single basepair substitutions in exons 2 and 6. Thus, relapse of PNH in this patient was not due to persistence of the original clones; rather, it was associated with the emergence of a new clone. These findings support the notion that the bone marrow environment may create selective conditions favoring the expansion of PNH clones. The changes found in the archival material included a 211A-G transition in exon 2, causing a thr71-to-ala substitution, and a 251C-T transition in exon 2, causing a thr84-to-ile substitution. The former change was present in 50% of clones and the latter change was present in 28% of those clones as a second mutation, suggesting that the latter mutation arose in a cell belonging to the clone that had the former mutation. A third mutation in exon 2, a 16G-T transversion causing a gly6-to-ter substitution, was present in 14% of clones. The finding of multiple mutational clones, as was the case after relapse, is not unusual in PNH. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, ARG412TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906726,
|
|
|
|
|
|
|
|
ClinVar: RCV000022881, RCV001007979
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing of the X chromosome in a family with multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2; 300868), Johnston et al. (2012) identified a 1234C-T transition in the last exon of the PIGA gene, resulting in an arg412-to-ter (R412X) substitution and truncation of the final C-terminal 109 amino acids. The mutation was not found in multiple large control sets. In vitro functional expression studies in PIGA-null cell lines showed that the R412X mutant protein retained some residual activity with partial restoration of GPI-anchored proteins, suggesting that it is not a null allele. The findings indicated that GPI anchors are important for normal development, particularly of the central nervous system. The patients had onset of seizures associated with burst-suppression pattern on EEG in the first weeks of life; both died by 11 weeks of age. The findings were consistent with a developmental and epileptic encephalopathy (DEE). </p><p>Kato et al. (2014) identified the R412X mutation in a 6-year-old Japanese boy with MCAHS2 manifest as early infantile epileptic encephalopathy with a clinical diagnosis of Ohtahara syndrome. He had severe disability, myoclonus, and quadriplegia. In vitro functional expression studies showed that the mutant protein could partially restore GPI-anchored protein expression in PIGA-null cells, suggesting that a small amount of full-length protein was generated by read-through of the stop codon. </p><p>Fauth et al. (2016) identified a hemizygous R412X mutation (c.1234C-T, NM_002641.3) in 4 affected males from 3 unrelated families with MCAHS2. One of the families had been reported by Terespolsky et al. (1995) and originally classified as having Simpson-Golabi-Behmel syndrome type 2 (SGBS2; 300209). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 1-BP DUP, 76T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777397,
|
|
|
|
|
|
|
|
ClinVar: RCV000119284
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 24-year-old man with MCAHS2 (300868) manifest as developmental and epileptic encephalopathy, Belet et al. (2014) identified a hemizygous 1-bp duplication (c.76dupT) in exon 2 of the PIGA gene, resulting in a frameshift and premature termination (Tyr26LeufsTer3). The family had previously been reported by Claes et al. (1997) as having West syndrome. The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in the 1000 Genomes Project, dbSNP (build 135), or Exome Variant Server databases, or in an in-house control database. Patient cells showed normal PIGA expression due to the production of a normal shorter PIGA isoform that lacks exon 2. Patient cells showed normal expression of CD59 (107271), and complementation assays showed that this shorter PIGA cDNA was able to partially rescue the surface expression of CD59 in a PIGA-null cell line. Belet et al. (2014) suggested that the mutation was a hypomorph that could rescue lethality in males, but could not compensate for the MCAHS2 phenotype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, ARG77LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777398,
|
|
|
|
|
|
|
|
ClinVar: RCV000119285
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Japanese brothers with MCAHS2 (300868) manifest as developmental and epileptic encephalopathy, Kato et al. (2014) identified a hemizygous c.230G-T transversion in exon 2 of the PIGA gene, resulting in an arg77-to-leu (R77L) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was not found in the Exome Variant Server database or in 573 in-house control exomes. In vitro functional expression studies showed that the mutant protein could partially restore GPI-anchored protein expression in PIGA-null cells. The patients had a slightly less severe phenotype than other patients with PIGA mutations (see, e.g., 311770.0011 and 311770.0014), which correlated with more residual PIGA enzymatic activity for the R77L protein. The patients had onset of seizures at 7 months of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, ILE206PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs201119959,
|
|
|
|
|
|
gnomAD: rs201119959,
|
|
|
|
|
|
ClinVar: RCV000119286
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese boy with MCAHS2 (300868) manifest as West syndrome, Kato et al. (2014) identified a hemizygous c.6161A-T transversion in exon 2 of the PIGA gene, resulting in an ile206-to-phe (I206F) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was not found in the Exome Variant Server database or in 573 in-house control exomes. In vitro functional expression studies showed that the mutant protein could partially restore GPI-anchored protein expression in PIGA-null cells. The patient had onset of seizures at 6 months of age; the phenotype was consistent with a developmental and epileptic encephalopathy (DEE). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, ARG119TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777396,
|
|
|
|
|
|
|
|
ClinVar: RCV000119283, RCV000443275, RCV004820831
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-month-old Japanese boy with MCAHS2 (300868) manifest as West syndrome, Kato et al. (2014) identified a hemizygous c.355C-T transition in exon 2 of the PIGA gene, resulting in an arg119-to-trp (R119W) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was not found in the Exome Variant Server database or in 573 in-house control exomes. The patient had onset of seizures at 3 months of age; the phenotype was consistent with a developmental and epileptic encephalopathy (DEE). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, 3-BP DEL, 328CTT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777399,
|
|
|
|
|
|
|
|
ClinVar: RCV000478249, RCV002221150, RCV002281561
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected males from a family with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; 301072), Swoboda et al. (2014) identified a hemizygous in-frame 3-bp deletion (c.328_330delCTT, NM_020473.3) in the PIGA gene, resulting in the deletion of a conserved residue (leu110del). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not present in the 1000 Genomes Project or Exome Variant Server databases. Flow cytometric analysis of the proband's granulocytes showed decreased cell surface levels of some GPI-anchored proteins, although CD59 (107271) expression on red blood cells was normal, suggesting that the mutant protein had some residual activity. In addition to neurologic features, the patients had cutaneous abnormalities and evidence of systemic iron overload. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, PRO93LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777400,
|
|
|
|
|
|
|
|
ClinVar: RCV000119288
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with MCAHS2 (300868), van der Crabben et al. (2014) identified a hemizygous c.278C-T transition in the PIGA gene, resulting in a pro93-to-leu (P93L) substitution in a highly conserved GPI-anchored biosynthesis domain region. The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP (build 137) or Exome Variant Server databases, or in 100 in-house control exomes. The mother and maternal grandmother were unaffected carriers, and the mother showed 100% skewing of the X-chromosome harboring the mutation. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, ARG77GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777398,
|
|
|
|
|
|
|
|
ClinVar: RCV000999330, RCV002221259
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 13-year-old boy (patient 1) with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; 301072), Muckenthaler et al. (2022) identified a hemizygous c.230G-A transition in the PIGA gene, resulting in an arg77-to-gln (R77Q) substitution. The mutation, which was found by exome sequencing, was inherited from the unaffected mother. In vitro functional expression studies showed that the mutation resulted in a partial loss of PIGA function with decreased levels of certain GPI-anchored proteins involved in iron homeostasis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, LEU344PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs761007687,
|
|
|
|
|
|
|
|
ClinVar: RCV000512946, RCV002221237
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy (patient 2) with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; 301072), Muckenthaler et al. (2022) identified a hemizygous c.1031T-C transition in the PIGA gene, resulting in a leu344-to-pro (L344P) substitution. The mutation, which was found by next-generation panel sequencing, was inherited from the unaffected mother. In vitro functional expression studies showed that the mutation resulted in a partial loss of PIGA function with decreased levels of certain GPI-anchored proteins involved in iron homeostasis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 NEURODEVELOPMENTAL DISORDER WITH EPILEPSY AND HEMOCHROMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PIGA, SER127LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2147723740,
|
|
|
|
|
|
|
|
ClinVar: RCV002221186
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old boy (patient 3) with neurodevelopmental disorder with epilepsy and hemochromatosis (NEDEPH; 301072), Muckenthaler et al. (2022) identified a hemizygous c.380C-T transition in the PIGA gene, resulting in a ser127-to-leu (S127L) substitution. The mutation, which was found by next-generation panel sequencing, was inherited from the unaffected mother. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be a hypomorphic allele. </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">
|
|
Araten, D. J., Nafa, K., Pakdeesuwan, K., Luzzatto, L.
|
|
<strong>Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 5209-5214, 1999.
|
|
|
|
|
|
[PubMed: 10220445]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.9.5209]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G.
|
|
<strong>Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.</strong>
|
|
Hum. Mutat. 35: 350-355, 2014.
|
|
|
|
|
|
[PubMed: 24357517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22498]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bessler, M., Mason, P. J., Hillmen, P., Miyata, T., Yamada, N., Takeda, J., Luzzatto, L., Kinoshita, T.
|
|
<strong>Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene.</strong>
|
|
EMBO J. 13: 110-117, 1994.
|
|
|
|
|
|
[PubMed: 8306954]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06240.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brodsky, R. A., Vala, M. S., Barber, J. P., Medof, M. E., Jones, R. J.
|
|
<strong>Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 8756-8760, 1997.
|
|
|
|
|
|
[PubMed: 9238050]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.16.8756]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brodsky, R. A.
|
|
<strong>Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood Rev. 22: 65-74, 2008.
|
|
|
|
|
|
[PubMed: 18063459]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.blre.2007.10.002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Claes, S., Devriendt, K., Lagae, L., Ceulemans, B., Dom, L., Casaer, P., Raeymaekers, P., Cassiman, J. J., Fryns, J. P.
|
|
<strong>The X-linked infantile spasms syndrome (MIM 308350) maps to Xp11.4-Xpter in two pedigrees.</strong>
|
|
Ann. Neurol. 42: 360-364, 1997.
|
|
|
|
|
|
[PubMed: 9307258]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410420313]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fauth, C., Steindl, K., Toutain, A., Farrell, S., Witsch-Baumgartner, M., Karall, D., Joset, P., Bohm, S., Baumer, A., Maier, O., Zschocke, J., Weksberg, R., Marshall, C. R., Rauch, A.
|
|
<strong>A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2.</strong>
|
|
Am. J. Med. Genet. 170A: 392-402, 2016.
|
|
|
|
|
|
[PubMed: 26545172]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.37452]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirose, S., Mohney, R. P., Mutka, S. C., Ravi, L., Singleton, D. R., Perry, G., Tartakoff, A. M., Medof, M. E.
|
|
<strong>Derivation and characterization of glycoinositol-phospholipid anchor-defective human K562 cell clones.</strong>
|
|
J. Biol. Chem. 267: 5272-5278, 1992.
|
|
|
|
|
|
[PubMed: 1371997]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hu, R., Mukhina, G. L., Piantadosi, S., Barber, J. P., Jones, R. J., Brodsky, R. A.
|
|
<strong>PIG-A mutations in normal hematopoiesis.</strong>
|
|
Blood 105: 3848-3854, 2005.
|
|
|
|
|
|
[PubMed: 15687243]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2004-04-1472]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iida, Y., Takeda, J., Miyata, T., Inoue, N., Nishimura, J., Kitani, T., Maeda, K., Kinoshita, T.
|
|
<strong>Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 83: 3126-3131, 1994.
|
|
|
|
|
|
[PubMed: 8193350]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnston, J. J., Gropman, A. L., Sapp, J. C., Teer, J. K., Martin, J. M., Liu, C. F., Yuan, X., Ye, Z., Cheng, L., Brodsky, R. A., Biesecker, L. G.
|
|
<strong>The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Am. J. Hum. Genet. 90: 295-300, 2012.
|
|
|
|
|
|
[PubMed: 22305531]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2011.11.031]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N.
|
|
<strong>PIGA mutations cause early-onset epileptic encephalopathies and distinctive features.</strong>
|
|
Neurology 82: 1587-1596, 2014.
|
|
|
|
|
|
[PubMed: 24706016]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000000389]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawagoe, K., Takeda, J., Endo, Y., Kinoshita, T.
|
|
<strong>Molecular cloning of murine Pig-a, a gene for GPI-anchor biosynthesis, and demonstration of interspecies conservation of its structure, function, and genetic locus.</strong>
|
|
Genomics 23: 566-574, 1994.
|
|
|
|
|
|
[PubMed: 7851884]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1544]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keller, P., Tremml, G., Rosti, V., Bessler, M.
|
|
<strong>X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 7479-7483, 1999.
|
|
|
|
|
|
[PubMed: 10377440]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.13.7479]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luzzatto, L., Bessler, M., Rotoli, B.
|
|
<strong>Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise?</strong>
|
|
Cell 88: 1-4, 1997.
|
|
|
|
|
|
[PubMed: 9019395]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81850-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luzzatto, L., Bessler, M.
|
|
<strong>The dual pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Curr. Opin. Hemat. 3: 101-110, 1996.
|
|
|
|
|
|
[PubMed: 9372059]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00062752-199603020-00001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maugard, C., Margueritte, G., Tuffery, S., Rabesandratana, H., Demaille, J., Claustres, M.
|
|
<strong>Recurrent PIG-A mutation (IVS5+1G-A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test.</strong>
|
|
Brit. J. Haemat. 98: 21-24, 1997.
|
|
|
|
|
|
[PubMed: 9233558]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.1997.1742988.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miyata, T., Takeda, J., Iida, Y., Yamada, N., Inoue, N., Takahashi, M., Maeda, K., Kitani, T., Kinoshita, T.
|
|
<strong>The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.</strong>
|
|
Science 259: 1318-1320, 1993.
|
|
|
|
|
|
[PubMed: 7680492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7680492]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miyata, T., Yamada, N., Iida, Y., Nishimura, J., Takeda, J., Kitani, T., Kinoshita, T.
|
|
<strong>Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
New Eng. J. Med. 330: 249-255, 1994.
|
|
|
|
|
|
[PubMed: 8272086]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199401273300404]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muckenthaler, L., Marques, O., Colucci, S., Kunz, J., Fabrowski, P., Bast, T., Altamura, S., Hochsmann, B., Schrezenmeier, H., Langlotz, M., Richter-Pechanska, P., Rausch, T., Hofmeister-Mielke, N., Gunkel, N., Hentze, M. W., Kulozik, A. E., Muckenthaler, M. U.
|
|
<strong>Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction.</strong>
|
|
Blood 139: 1418-1422, 2022.
|
|
|
|
|
|
[PubMed: 34875027]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.2021013519]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nafa, K., Bessler, M., Castro-Malaspina, H., Jhanwar, S., Luzzatto, L.
|
|
<strong>The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal hemoglobinuria includes large deletions and small duplications.</strong>
|
|
Blood Cells Molec. Dis. 24: 370-384, 1998.
|
|
|
|
|
|
[PubMed: 10087994]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bcmd.1998.0203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nafa, K., Bessler, M., Deeg, H. J., Luzzatto, L.
|
|
<strong>New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 92: 3422-3427, 1998.
|
|
|
|
|
|
[PubMed: 9787183]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nafa, K., Mason, P. J., Hillmen, P., Luzzatto, L., Bessler, M.
|
|
<strong>Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type.</strong>
|
|
Blood 86: 4650-4655, 1995.
|
|
|
|
|
|
[PubMed: 8541557]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagarajan, S., Brodsky, R. A., Young, N. S., Medof, M. E.
|
|
<strong>Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia.</strong>
|
|
Blood 86: 4656-4661, 1995.
|
|
|
|
|
|
[PubMed: 8541558]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagarajan, S., Brown, C. J., Medof, M. E.
|
|
<strong>Identification of a PIG-A related processed gene on chromosome 12.</strong>
|
|
Hum. Genet. 95: 691-697, 1995.
|
|
|
|
|
|
[PubMed: 7654280]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00209489]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ogata, T., Wakui, K., Muroya, K., Ohashi, H., Matsuo, N., Brown, D. M., Ishii, T., Fukushima, Y.
|
|
<strong>Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern.</strong>
|
|
Hum. Genet. 103: 51-56, 1998.
|
|
|
|
|
|
[PubMed: 9737776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050782]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosse, W. F.
|
|
<strong>Personal Communication.</strong>
|
|
Durham, N. C. 6/3/1993.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sauer, B., Henderson, N.
|
|
<strong>Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 5166-5170, 1988.
|
|
|
|
|
|
[PubMed: 2839833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.85.14.5166]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Savoia, A., Ianzano, L., Lunardi, C., De Sandre, G., Carotenuto, M., Musto, P., Zelante, L.
|
|
<strong>Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients.</strong>
|
|
Hum. Genet. 97: 45-48, 1996.
|
|
|
|
|
|
[PubMed: 8557259]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00218831]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stevens, V. L., Raetz, C. R. H.
|
|
<strong>Defective glycosyl phosphatidylinositol biosynthesis in extracts of three thy-1 negative lymphoma cell mutants.</strong>
|
|
J. Biol. Chem. 266: 10039-10042, 1991.
|
|
|
|
|
|
[PubMed: 1828068]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sugiyama, E., DeGasperi, R., Urakaze, M., Chang, H.-M., Thomas, L. J., Hyman, R., Warren, C. D., Yeh, E. T. H.
|
|
<strong>Identification of defects in glycosylphosphatidylinositol anchor biosynthesis in the thy-1 expression mutants.</strong>
|
|
J. Biol. Chem. 266: 12119-12122, 1991.
|
|
|
|
|
|
[PubMed: 1829456]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swoboda, K. J., Margraf, R. L., Carey, J. C., Zhou, H., Newcomb, T. M., Coonrod, E., Durtschi, J., Mallempati, K., Kumanovics, A., Katz, B. E., Voelkerding, K. V., Opitz, J. M.
|
|
<strong>A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload.</strong>
|
|
Am. J. Med. Genet. 164A: 17-28, 2014.
|
|
|
|
|
|
[PubMed: 24259288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.36189]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takahashi, M., Takeda, J., Hirose, S., Hyman, R., Inoue, N., Miyata, T., Ueda, E., Kitani, T., Medof, M. E., Kinoshita, T.
|
|
<strong>Deficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
J. Exp. Med. 177: 517-521, 1993.
|
|
|
|
|
|
[PubMed: 8426120]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.177.2.517]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., Kinoshita, T.
|
|
<strong>Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Cell 73: 703-711, 1993.
|
|
|
|
|
|
[PubMed: 8500164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(93)90250-t]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Terespolsky, D., Farrell, S. A., Siegel-Bartelt, J., Weksberg, R.
|
|
<strong>Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis.</strong>
|
|
Am. J. Med. Genet. 59: 329-333, 1995.
|
|
|
|
|
|
[PubMed: 8599356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320590310]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ueda, E., Nishimura, J., Kitani, T., Nasu, K., Kageyama, T., Kim, Y. U., Takeda, J., Kinoshita, T.
|
|
<strong>Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Int. Immun. 4: 1263-1271, 1992.
|
|
|
|
|
|
[PubMed: 1282030]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/intimm/4.11.1263]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van der Crabben, S. N., Harakalova, M., Brilstra, E. H., van Berkestijn, F. M. C., Hofstede, F. C., van Vught, A. J., Cuppen, E., Kloosterman, W., Ploos van Amstel, H. K., van Haaften, G., van Haelst, M. M.
|
|
<strong>Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.</strong>
|
|
Am. J. Med. Genet. 164A: 29-35, 2014.
|
|
|
|
|
|
[PubMed: 24259184]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.36184]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ware, R. E., Howard, T. A., Kamitani, T., Chang, H.-M., Yeh, E. T. H., Seldin, M. F.
|
|
<strong>Chromosomal assignment of genes involved in glycosylphosphatidylinositol anchor biosynthesis: implications for the pathogenesis of paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 83: 3753-3757, 1994.
|
|
|
|
|
|
[PubMed: 8204896]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ware, R. E., Rosse, W. F., Howard, T. A.
|
|
<strong>Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria.</strong>
|
|
Blood 83: 2418-2422, 1994.
|
|
|
|
|
|
[PubMed: 8167330]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Watanabe, R., Inoue, N., Westfall, B., Taron, C. H., Orlean, P., Takeda, J., Kinoshita, T.
|
|
<strong>The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.</strong>
|
|
EMBO J. 17: 877-885, 1998.
|
|
|
|
|
|
[PubMed: 9463366]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/17.4.877]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Watanabe, R., Kinoshita, T., Masaki, R., Yamamoto, A., Takeda, J., Inoue, N.
|
|
<strong>PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 271: 26868-26875, 1996.
|
|
|
|
|
|
[PubMed: 8900170]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.271.43.26868]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu, J., Nagarajan, S., Ueda, E., Knez, J. J., Petersen, R. B., Medof, M. E.
|
|
<strong>Characterization of alternatively spliced PIG-A transcripts in normal and paroxysmal nocturnal hemoglobinuria cells.</strong>
|
|
Braz. J. Med. Biol. Res. 27: 195-201, 1994.
|
|
|
|
|
|
[PubMed: 8081230]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 03/23/2022<br>Matthew B. Gross - updated : 01/10/2018<br>Cassandra L. Kniffin - updated : 3/29/2016<br>Cassandra L. Kniffin - updated : 5/21/2014<br>Cassandra L. Kniffin - updated : 2/28/2012<br>Matthew B. Gross - updated : 7/1/2010<br>Victor A. McKusick - updated : 8/31/2005<br>Victor A. McKusick - updated : 6/20/2005<br>Victor A. McKusick - updated : 2/24/2004<br>Victor A. McKusick - updated : 1/21/2003<br>Victor A. McKusick - updated : 2/22/2002<br>Dawn Watkins-Chow - updated : 3/22/2001<br>Victor A. McKusick - updated : 2/18/2000<br>Victor A. McKusick - updated : 1/21/2000<br>Victor A. McKusick - updated : 7/19/1999<br>Victor A. McKusick - updated : 2/27/1999<br>Victor A. McKusick - updated : 2/27/1999<br>Victor A. McKusick - updated : 9/16/1997<br>Victor A. McKusick - updated : 9/12/1997<br>Jennifer P. Macke - updated : 5/27/1997<br>Victor A. McKusick - edited : 3/7/1997<br>Victor A. McKusick - updated : 2/11/1997<br>Cynthia K. Ewing - updated : 10/14/1996<br>Stylianos E. Antonarakis - updated : 7/8/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/8/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 03/25/2024<br>carol : 04/07/2022<br>alopez : 04/05/2022<br>ckniffin : 03/23/2022<br>alopez : 10/13/2020<br>ckniffin : 10/08/2020<br>mgross : 01/10/2018<br>mgross : 04/25/2016<br>carol : 3/31/2016<br>alopez : 3/30/2016<br>ckniffin : 3/29/2016<br>carol : 3/9/2015<br>alopez : 5/22/2014<br>mcolton : 5/22/2014<br>ckniffin : 5/21/2014<br>carol : 3/2/2012<br>ckniffin : 2/28/2012<br>carol : 7/2/2010<br>mgross : 7/1/2010<br>mgross : 7/1/2010<br>mgross : 7/1/2010<br>terry : 7/26/2006<br>wwang : 8/31/2005<br>terry : 8/31/2005<br>terry : 8/3/2005<br>alopez : 6/22/2005<br>terry : 6/20/2005<br>ckniffin : 7/15/2004<br>carol : 3/17/2004<br>tkritzer : 2/26/2004<br>terry : 2/24/2004<br>cwells : 1/24/2003<br>cwells : 1/24/2003<br>tkritzer : 1/21/2003<br>tkritzer : 1/21/2003<br>cwells : 3/13/2002<br>cwells : 3/11/2002<br>terry : 2/22/2002<br>carol : 3/22/2001<br>carol : 3/22/2001<br>mgross : 3/16/2000<br>terry : 2/18/2000<br>carol : 2/2/2000<br>terry : 1/21/2000<br>mcapotos : 12/8/1999<br>alopez : 7/28/1999<br>terry : 7/19/1999<br>terry : 3/1/1999<br>carol : 2/27/1999<br>carol : 2/27/1999<br>dkim : 9/11/1998<br>alopez : 5/21/1998<br>carol : 3/10/1998<br>jenny : 9/19/1997<br>terry : 9/16/1997<br>terry : 9/12/1997<br>alopez : 7/24/1997<br>alopez : 7/24/1997<br>alopez : 6/3/1997<br>alopez : 4/4/1997<br>alopez : 4/3/1997<br>mark : 3/7/1997<br>terry : 2/11/1997<br>terry : 2/4/1997<br>mark : 1/3/1997<br>terry : 12/16/1996<br>jenny : 12/12/1996<br>terry : 12/9/1996<br>jamie : 10/23/1996<br>jamie : 10/16/1996<br>jamie : 10/14/1996<br>mark : 7/8/1996<br>mark : 3/11/1996<br>terry : 3/4/1996<br>mark : 1/14/1996<br>carol : 12/13/1994<br>terry : 10/19/1994<br>jason : 7/12/1994<br>warfield : 4/20/1994<br>mimadm : 2/28/1994<br>carol : 8/31/1993
|
|
</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 12, 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>
|
|
|
|
|