3714 lines
286 KiB
Text
3714 lines
286 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
|
|
|
|
- #176200 - VARIEGATE PORPHYRIA; VP
|
|
|
|
|
|
- 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=176200"><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">#176200</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/176200"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#diagnosis">Diagnosis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalManagement">Clinical Management</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=VARIEGATE PORPHYRIA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11499&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK121283/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/7355" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=176200[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79473" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</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/disease/DOID:4346" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/disease/176200" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA000815/" 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>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:176200" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 58275005<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 79473<br />
|
|
|
|
|
|
<strong>DO:</strong> 4346<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
176200
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
VARIEGATE PORPHYRIA; VP
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
PORPHYRIA VARIEGATA<br />
|
|
PORPHYRIA, SOUTH AFRICAN TYPE<br />
|
|
PROTOPORPHYRINOGEN OXIDASE DEFICIENCY<br />
|
|
PPOX DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1341?start=-3&limit=10&highlight=1341">
|
|
1q23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Variegate porphyria
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/176200"> 176200 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
PPOX
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600923"> 600923 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/176200" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/176200" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/176200" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Tachycardia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86651002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86651002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3424008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3424008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R00.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/785.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">785.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3827868&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3827868</a>, <a href="https://bioportal.bioontology.org/search?q=C0039231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001649" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001649</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001649" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001649</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Abdominal pain <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/21522001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">21522001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R10.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R10.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/789.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0000737&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0000737</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002027" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002027</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002027" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002027</a>]</span><br /> -
|
|
Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br /> -
|
|
Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Photosensitivity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90128006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90128006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349506&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349506</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000992" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000992</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000992" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000992</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Psychosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/191525009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">191525009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/69322001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">69322001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F29" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F29</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/298.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">298.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/290-299.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290-299.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349204&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349204</a>, <a href="https://bioportal.bioontology.org/search?q=C0033975&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033975</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000709" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000709</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000709" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000709</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Muscular paralysis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0553727&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0553727</a>]</span><br /> -
|
|
Neuropathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386033004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386033004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G62.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G62.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0442874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0442874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009830</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009830</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Elevated fecal levels of protoporphyrin and coproporphyrin at all times <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867935</a>]</span><br /> -
|
|
Increased urine porphyrins at times <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867936&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867936</a>]</span><br /> -
|
|
Increased urinary porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) during acute attacks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867937&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867937</a>]</span><br /> -
|
|
Reduced (50%) activity of protoporphyrinogen oxidase (PROTO oxidase)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset in 2nd decade<br /> -
|
|
Attacks often drug-induced<br /> -
|
|
Common in South African whites<br /> -
|
|
Skin manifestation less frequently observed in cold climates<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the protoporphyrinogen oxidase gene (PPOX, <a href="/entry/600923#0001">600923.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that variegate porphyria (VP) is caused by heterozygous mutation in the gene encoding protoporphyrinogen oxidase (PPOX; <a href="/entry/600923">600923</a>) on chromosome 1q23.</p><p>Biallelic mutation in the PPOX gene causes a childhood-onset form of variegate porphyria (VPCO; <a href="/entry/620483">620483</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Variegate porphyria (VP) is characterized by cutaneous manifestations, including increased photosensitivity, blistering, skin fragility with chronic scarring of sun-exposed areas, and postinflammatory hyperpigmentation. Acute exacerbations of VP include abdominal pain, the passage of dark urine, and neuropsychiatric symptoms that characterize the acute hepatic porphyrias, such as bulbar paralysis, quadriplegia, motor neuropathy, and weakness of the limbs. VP is inherited as an autosomal dominant trait with incomplete penetrance. Clinical manifestations do not usually present before puberty, and PPOX activity is decreased by about 50% (summary by <a href="#9" class="mim-tip-reference" title="Frank, J., Jugert, F. K., Breitkopf, C., Goerz, G., Merk, H. F., Christiano, A. M. <strong>Recurrent missense mutation in the protoporphyrinogen oxidase gene underlies variegate porphyria.</strong> Am. J. Med. Genet. 79: 22-26, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9738863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9738863</a>]" pmid="9738863">Frank et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9738863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Adults with variegate porphyria show a variable picture of skin symptoms, including hyperpigmentation and hypertrichosis, associated with acute attacks like those of acute intermittent porphyria (<a href="/entry/176000">176000</a>). Attacks may be protracted and followed by prolonged disability. Attacks are often drug-induced and show the classic neuropathic symptoms and signs, such as abdominal pain, constipation, tachycardia and hypertension, and muscular paralysis and sensory disturbances; disorientation and frank psychosis may be conspicuous features. The condition is characterized by elevated fecal levels of protoporphyrin and coproporphyrin at all times, with increased urine porphyrins at times, and an increase in urinary levels of the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) during the acute attack (<a href="#7" class="mim-tip-reference" title="Dean, G. <strong>The Porphyrias. A Story of Inheritance and Environment. (2nd ed.)</strong> Philadelphia: J. B. Lippincott (pub.) 1972."None>Dean, 1972</a>; <a href="#23" class="mim-tip-reference" title="Mustajoki, P. <strong>Variegate porphyria.</strong> Ann. Intern. Med. 89: 238-244, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/677592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">677592</a>] [<a href="https://doi.org/10.7326/0003-4819-89-2-238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="677592">Mustajoki, 1978</a>; <a href="#22" class="mim-tip-reference" title="Meyer, U. A., Schmid, R. <strong>The porphyrias. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.): The Metabolic Basis of Inherited Disease. (4th ed.)</strong> New York: McGraw-Hill (pub.) 1978. Pp. 1166-1220."None>Meyer and Schmid, 1978</a>). Iron overload is a well-established precipitating or aggravating factor in porphyria variegata. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=677592" 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="Frank, J., Jugert, F. K., Breitkopf, C., Goerz, G., Merk, H. F., Christiano, A. M. <strong>Recurrent missense mutation in the protoporphyrinogen oxidase gene underlies variegate porphyria.</strong> Am. J. Med. Genet. 79: 22-26, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9738863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9738863</a>]" pmid="9738863">Frank et al. (1998)</a> reported 2 unrelated patients with variegate porphyria and mutation in the PPOX gene. Proband 1 was a 57-year-old woman of German ancestry who developed a life-threatening acute porphyric attack with paralysis at around 30 years of age. At that time the diagnosis of acute intermittent porphyria was rendered on the basis of clinical and biochemical findings. Thereafter she experienced recurrent colicky abdominal pain, vomiting, and mental confusion. Upon sun exposure, small blisters developed on the forearms and the back of the hands that left chronic hyperpigmented scars. The diagnosis of variegate porphyria was made on the basis of the cutaneous symptoms and porphyrin analysis of the feces. Proband 2 was a 38-year-old woman of Armenian and North American ancestry who was diagnosed with variegate porphyria on the basis of clinical and biochemical findings; no clinical details were provided. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9738863" 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="#5" class="mim-tip-reference" title="Collantes-Rodriguez, C., de la Varga-Martinez, R., Villegas-Romero, I., Jimenez-Gallo, D., Linares-Barrios, M., Mora-Lopez, F. <strong>Two new mutations in the PPOX gene in a patient with variegate porphyria.</strong> J. Dtsch. Derm. Ges. 18: 381-383, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32247286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32247286</a>] [<a href="https://doi.org/10.1111/ddg.14079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32247286">Collantes-Rodriguez et al. (2020)</a> reported a 25-year-old Spanish man with a 5-year history of blistering skin lesions on the backs of his hands, associated with hyperpigmentation and hypertrichosis and exacerbation in spring and summer. He had no systemic symptoms. There was a maternal family history of similar lesions without associated systemic symptoms. Biochemical analysis showed elevated uroporphyrin and the presence of coproporphyrin and protoporphyrin in the proband's feces. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32247286" 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="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The basic defect appears to be reduction in the activity of the enzyme protoporphyrinogen oxidase to approximately 50% of the normal level as determined in skin fibroblasts (<a href="#3" class="mim-tip-reference" title="Brenner, D. A., Bloomer, J. R. <strong>The enzymatic defect in variegate porphyria: studies with human cultured skin fibroblasts.</strong> New Eng. J. Med. 302: 765-769, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7354807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7354807</a>] [<a href="https://doi.org/10.1056/NEJM198004033021401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7354807">Brenner and Bloomer, 1980</a>) and presumably in other tissues, especially liver. This enzymopathy is unusual in being the effect of a single gene dose, rather than requiring a double dose for its expression. Several other genetic porphyrias share this effect; see <a href="/entry/121300">121300</a>, <a href="/entry/176000">176000</a>, and <a href="/entry/176100">176100</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7354807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="diagnosis" class="mim-anchor"></a>
|
|
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#18" class="mim-tip-reference" title="Logan, G. M., Weimer, M. K., Ellefson, M., Pierach, C. A., Bloomer, J. R. <strong>Bile porphyrin analysis in the evaluation of variegate porphyria.</strong> New Eng. J. Med. 324: 1408-1411, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2020296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2020296</a>] [<a href="https://doi.org/10.1056/NEJM199105163242005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2020296">Logan et al. (1991)</a> noted that biochemical confirmation of the diagnosis of variegate porphyria can be difficult, particularly in patients without neurologic dysfunction at the time of testing. Levels of porphyrin in the stool may be normal because food and bacterial metabolism in the intestine contribute to the porphyrin content of the feces and may obscure the differences in levels between normal and affected persons. To overcome this shortcoming, <a href="#18" class="mim-tip-reference" title="Logan, G. M., Weimer, M. K., Ellefson, M., Pierach, C. A., Bloomer, J. R. <strong>Bile porphyrin analysis in the evaluation of variegate porphyria.</strong> New Eng. J. Med. 324: 1408-1411, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2020296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2020296</a>] [<a href="https://doi.org/10.1056/NEJM199105163242005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2020296">Logan et al. (1991)</a> measured porphyrin levels in the bile and found considerably greater differences in bile levels than in fecal levels in patients and normals. <a href="#17" class="mim-tip-reference" title="Kushner, J. P. <strong>Laboratory diagnosis of the porphyrias. (Editorial)</strong> New Eng. J. Med. 324: 1432-1434, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2020301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2020301</a>] [<a href="https://doi.org/10.1056/NEJM199105163242010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2020301">Kushner (1991)</a> reviewed the laboratory diagnosis of the porphyrias. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2020296+2020301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalManagement" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Management of porphyria consists primarily of avoidance of porphyrinogenic agents and protection for photosensitive skin (<a href="#17" class="mim-tip-reference" title="Kushner, J. P. <strong>Laboratory diagnosis of the porphyrias. (Editorial)</strong> New Eng. J. Med. 324: 1432-1434, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2020301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2020301</a>] [<a href="https://doi.org/10.1056/NEJM199105163242010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2020301">Kushner, 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2020301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#4" class="mim-tip-reference" title="Cochrane, A. L., Goldberg, A. <strong>A study of faecal porphyrin levels in a large family.</strong> Ann. Hum. Genet. 32: 195-208, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5715631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5715631</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1968.tb00064.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5715631">Cochrane and Goldberg (1968)</a> reported studies of an extensive kindred of which the first author was a member. Children and asymptomatic adults showed the chemical features without manifest disease, but allowed the demonstration that porphyria variegata segregates is an autosomal dominant trait, with manifestation in about one half of affected adults (<a href="#4" class="mim-tip-reference" title="Cochrane, A. L., Goldberg, A. <strong>A study of faecal porphyrin levels in a large family.</strong> Ann. Hum. Genet. 32: 195-208, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5715631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5715631</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1968.tb00064.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5715631">Cochrane and Goldberg, 1968</a>; <a href="#7" class="mim-tip-reference" title="Dean, G. <strong>The Porphyrias. A Story of Inheritance and Environment. (2nd ed.)</strong> Philadelphia: J. B. Lippincott (pub.) 1972."None>Dean, 1972</a>; <a href="#11" class="mim-tip-reference" title="Hamnstrom, B., Haeger-Aronsen, B., Waldenstrom, J., Hysing, B., Molander, J. <strong>Three Swedish families with porphyria variegata.</strong> Brit. Med. J. 4: 449-453, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6055732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6055732</a>] [<a href="https://doi.org/10.1136/bmj.4.5577.449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6055732">Hamnstrom et al., 1967</a>; <a href="#10" class="mim-tip-reference" title="Fromke, V. L., Bossenmaier, I., Cardinal, R., Watson, C. J. <strong>Porphyria variegata: study of a large kindred in the United States.</strong> Am. J. Med. 65: 80-88, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/686004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">686004</a>] [<a href="https://doi.org/10.1016/0002-9343(78)90696-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="686004">Fromke et al., 1978</a>; <a href="#14" class="mim-tip-reference" title="Husquinet, H., Noirfalise, A., Parent, M.-T. <strong>Porphyria variegata: etude d'une grande famille.</strong> J. Genet. Hum. 26: 367-383, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/752067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">752067</a>]" pmid="752067">Husquinet et al., 1978</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=686004+752067+6055732+5715631" 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>VP is usually inherited as an autosomal dominant trait with incomplete penetrance (<a href="#9" class="mim-tip-reference" title="Frank, J., Jugert, F. K., Breitkopf, C., Goerz, G., Merk, H. F., Christiano, A. M. <strong>Recurrent missense mutation in the protoporphyrinogen oxidase gene underlies variegate porphyria.</strong> Am. J. Med. Genet. 79: 22-26, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9738863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9738863</a>]" pmid="9738863">Frank et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9738863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Porphyria variegata was observed in 3 families in Sweden by <a href="#11" class="mim-tip-reference" title="Hamnstrom, B., Haeger-Aronsen, B., Waldenstrom, J., Hysing, B., Molander, J. <strong>Three Swedish families with porphyria variegata.</strong> Brit. Med. J. 4: 449-453, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6055732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6055732</a>] [<a href="https://doi.org/10.1136/bmj.4.5577.449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6055732">Hamnstrom et al. (1967)</a>. No genealogic connection with any of the 600 known cases of acute intermittent porphyria could be shown. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6055732" 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="Dean, G. <strong>The Porphyrias. A Story of Inheritance and Environment. (2nd ed.)</strong> Philadelphia: J. B. Lippincott (pub.) 1972."None>Dean (1972)</a> described in an engaging manner his studies of porphyria in South Africa and comparative studies in Sweden, Holland, Turkey, and elsewhere. The high frequency of the gene for porphyria variegata in South Africa is a cardinal example of founder effect. <a href="#7" class="mim-tip-reference" title="Dean, G. <strong>The Porphyrias. A Story of Inheritance and Environment. (2nd ed.)</strong> Philadelphia: J. B. Lippincott (pub.) 1972."None>Dean (1972)</a> estimated that about 8,000 persons in South Africa were suffering from porphyria inherited from either Gerrit Jansz, a Dutch settler in the Cape, or his wife, Ariaantje Jacobs, who was 1 of 8 sent from an orphanage in Rotterdam to provide wives for Dutch settlers in the Cape. He estimated, furthermore, that 1 million of 3 million whites are descendants of 40 original settlers and their wives, a 12,000-fold increase. <a href="#26" class="mim-tip-reference" title="Stine, O. C., Smith, K. D. <strong>The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.</strong> Am. J. Hum. Genet. 46: 452-458, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2137963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2137963</a>]" pmid="2137963">Stine and Smith (1990)</a> calculated a coefficient of selection between 0.07 and 0.02 for the porphyria variegata gene in the Afrikaner population of South Africa. <a href="#15" class="mim-tip-reference" title="Jenkins, T. <strong>Medical genetics in South Africa.</strong> J. Med. Genet. 27: 760-779, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2074562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2074562</a>] [<a href="https://doi.org/10.1136/jmg.27.12.760" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2074562">Jenkins (1990)</a> gave a comprehensive review of medical genetics in South Africa; porphyria variegata was included in a listing of inherited conditions of unusual prevalence among some southern African populations. (See <a href="/entry/600923#0003">600923.0003</a> for the probable founder gene defect associated causally with VP in South Africa.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2137963+2074562" 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>Porphyria variegata is also frequent in Finland (<a href="#24" class="mim-tip-reference" title="Mustajoki, P. <strong>Variegate porphyria: twelve years' experience in Finland.</strong> Quart. J. Med. 49: 191-203, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7433635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7433635</a>]" pmid="7433635">Mustajoki, 1980</a>), where prevalence was estimated to be 1.3 per 100,000. Of 57 patients in 9 families, 18 had had acute attacks. During an average of 5.7 years' follow-up, only 2 of 48 patients had symptoms, which were temporary and acute. The longevity of gene carriers did not differ from that of the general population. Skin fragility occurred in 45% of patients and was usually mild. <a href="#24" class="mim-tip-reference" title="Mustajoki, P. <strong>Variegate porphyria: twelve years' experience in Finland.</strong> Quart. J. Med. 49: 191-203, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7433635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7433635</a>]" pmid="7433635">Mustajoki (1980)</a> concluded that variegate porphyria might be commoner than suspected, noting that only half of patients in temperate and cold climates have skin symptoms, the risk of developing an acute attack is low, and some adult patients excrete normal or only slightly abnormal amounts of porphyrin. Of 57 patients in 9 families, 18 had had acute attacks, but the longevity of gene carriers did not differ from that of the general population. Skin fragility was usually mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7433635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#1" class="mim-tip-reference" title="Bissbort, S., Hitzeroth, H. W., du Wentzel, D. P., Van den Berg, C. W., Senff, H., Wienker, T. F., Bender, K. <strong>Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14.</strong> Hum. Genet. 79: 289-290, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3261272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3261272</a>] [<a href="https://doi.org/10.1007/BF00366255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3261272">Bissbort et al. (1988)</a> demonstrated linkage between VP and alpha-1-antitrypsin (<a href="/entry/107400">107400</a>); the maximum lod score from male meioses was 4.33 at theta = 0.04, and from both sexes combined, 3.56 at theta = 0.12. In pedigrees triply informative for VP, PI and the Gm polymorphism, VP and PI cosegregated separately from Gm. These findings argued in favor of either gene order VP--PI--IGHC or PI--VP--IGHC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3261272" 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="Taketani, S., Inazawa, J., Abe, T., Furukawa, T., Kohno, H., Tokunaga, R., Nishimura, K., Inokuchi, H. <strong>The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1.</strong> Genomics 29: 698-703, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575762</a>] [<a href="https://doi.org/10.1006/geno.1995.9949" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575762">Taketani et al. (1995)</a> showed by Southern blotting of human genomic DNA that there is a single copy of the PPOX gene, and by fluorescence in situ hybridization they mapped the gene to 1q22 (see also <a href="/entry/600923">600923</a>). The reason for the discrepancy between linkage mapping of variegate porphyria to chromosome 14 by <a href="#1" class="mim-tip-reference" title="Bissbort, S., Hitzeroth, H. W., du Wentzel, D. P., Van den Berg, C. W., Senff, H., Wienker, T. F., Bender, K. <strong>Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14.</strong> Hum. Genet. 79: 289-290, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3261272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3261272</a>] [<a href="https://doi.org/10.1007/BF00366255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3261272">Bissbort et al. (1988)</a> and this location of the gene by fluorescence in situ hybridization is unexplained; however, <a href="#27" class="mim-tip-reference" title="Taketani, S., Inazawa, J., Abe, T., Furukawa, T., Kohno, H., Tokunaga, R., Nishimura, K., Inokuchi, H. <strong>The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1.</strong> Genomics 29: 698-703, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575762</a>] [<a href="https://doi.org/10.1006/geno.1995.9949" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575762">Taketani et al. (1995)</a> suggested that it is possible that an additional gene product on chromosome 14 may interact with PPOX protein to maintain the normal enzyme activity or to affect expression of the PPOX gene (thus accounting for the findings of <a href="#1" class="mim-tip-reference" title="Bissbort, S., Hitzeroth, H. W., du Wentzel, D. P., Van den Berg, C. W., Senff, H., Wienker, T. F., Bender, K. <strong>Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14.</strong> Hum. Genet. 79: 289-290, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3261272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3261272</a>] [<a href="https://doi.org/10.1007/BF00366255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3261272">Bissbort et al. (1988)</a> referred to earlier). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8575762+3261272" 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="#25" class="mim-tip-reference" title="Roberts, A. G., Whatley, S. D., Daniels, J., Holmans, P., Fenton, I., Owen, M. J., Thompson, P., Long, C., Elder, G. H. <strong>Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23.</strong> Hum. Molec. Genet. 4: 2387-2390, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634714</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2387" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634714">Roberts et al. (1995)</a> likewise mapped the PPOX gene to chromosome 1 (1q23) and showed that the clinical disorder variegate porphyria is linked to microsatellite and other markers in the region 1q21-q23. They concluded that the evidence spoke against locus heterogeneity in VP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Deybach, J.-C., Puy, H., Robreau, A.-M., Lamoril, J., Da Silva, V., Grandchamp, B., Nordmann, Y. <strong>Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria.</strong> Hum. Molec. Genet. 5: 407-410, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852667</a>] [<a href="https://doi.org/10.1093/hmg/5.3.407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8852667">Deybach et al. (1996)</a> investigated the molecular defect responsible for VP by sequencing the coding portions of the PPOX gene in 4 patients in 3 unrelated families of French Caucasian origin. In 1 patient, insertion of G at position 1022 of the cDNA produced a frameshift resulting in a premature stop codon (<a href="/entry/600923#0001">600923.0001</a>). In 3 other patients from 2 unrelated families, they found a missense mutation leading to substitution of arginine for glycine (G232R) in exon 7 (<a href="/entry/600923#0002">600923.0002</a>). In 1 of the latter families, consisting of 14 members over 3 generations, they demonstrated the cosegregation of the G232R mutation with deficient PPOX activity. This was the first report of mutations in patients with VP and supported the conclusion that PPOX gene defects cause variegate porphyria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852667" 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="Meissner, P. N., Dailey, T. A., Hift, R. J., Ziman, M., Corrigall, A. V., Roberts, A. G., Meissner, D. M., Kirsch, R. E., Dailey, H. A. <strong>A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria.</strong> Nature Genet. 13: 95-97, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673113</a>] [<a href="https://doi.org/10.1038/ng0596-95" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673113">Meissner et al. (1996)</a> described an arg59-to-trp (R59W) mutation in the PPOX gene (<a href="/entry/600923#0003">600923.0003</a>) in 43 of 45 patients with VP from 26 of 27 South African families investigated, but not in 34 unaffected relatives or 9 unrelated British patients with protoporphyrinogen oxidase deficiency. Since at least one of these families could be shown to be descended from the founder of South African VP, this defect may represent the founder gene defect associated causally with VP in South Africa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673113" 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="Warnich, L., Kotze, M. J., Groenewald, I. M., Groenewald, J. Z., van Brakel, M. G., van Heerden, C. J., de Villiers, J. N. P., van de Ven, W. J. M., Schoenmakers, E. F. P. M., Taketani, S., Retief, A. E. <strong>Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria.</strong> Hum. Molec. Genet. 5: 981-984, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817334</a>] [<a href="https://doi.org/10.1093/hmg/5.7.981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8817334">Warnich et al. (1996)</a> identified the R59W mutation in 15 of 17 South African patients with variegate porphyria. This mutation was shown to create a StyI restriction site and was found to be associated with C(26)-C(150), 1 of 4 potential haplotypes defined by 2 polymorphisms in exon 1 of the PPOX gene. <a href="#29" class="mim-tip-reference" title="Warnich, L., Kotze, M. J., Groenewald, I. M., Groenewald, J. Z., van Brakel, M. G., van Heerden, C. J., de Villiers, J. N. P., van de Ven, W. J. M., Schoenmakers, E. F. P. M., Taketani, S., Retief, A. E. <strong>Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria.</strong> Hum. Molec. Genet. 5: 981-984, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817334</a>] [<a href="https://doi.org/10.1093/hmg/5.7.981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8817334">Warnich et al. (1996)</a> reported that these data supported the founder hypothesis for variegate porphyria in South Africa. In 1 of 17 patients there was an exon 2 mutation (H20P; <a href="/entry/600923#0005">600923.0005</a>). This mutation was associated with the same exon 1 polymorphism haplotype as the R59W mutation. An exon 6 mutation, R168C (<a href="/entry/600923#0004">600923.0004</a>), was identified in 1 patient; this mutation abolished a DsaI restriction site in genomic DNA of affected individuals and was shown to be associated with a different haplotype for the exon 1 polymorphism, A(26)-C(150). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated women with variegate porphyria, <a href="#9" class="mim-tip-reference" title="Frank, J., Jugert, F. K., Breitkopf, C., Goerz, G., Merk, H. F., Christiano, A. M. <strong>Recurrent missense mutation in the protoporphyrinogen oxidase gene underlies variegate porphyria.</strong> Am. J. Med. Genet. 79: 22-26, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9738863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9738863</a>]" pmid="9738863">Frank et al. (1998)</a> analyzed exon 6 of the PPOX gene and identified heterozygosity for the same missense mutation (R168H; <a href="/entry/600923#0006">600923.0006</a>). Segregation analysis in the family of proband 1 revealed that her unaffected son also carried the R168H variant, indicating incomplete penetrance; relatives of proband 2 were unavailable for study. The mutation was not found in 50 unrelated controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9738863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="de Villiers, J. N. P., Hillermann, R., Loubser, L., Kotze, M. J. <strong>Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria.</strong> Hum. Molec. Genet. 8: 1517-1522, 1999. Note: Erratum: Hum. Molec. Genet. 8: 1817 only, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10401000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10401000</a>] [<a href="https://doi.org/10.1093/hmg/8.8.1517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10401000">De Villiers et al. (1999)</a> identified a South African patient with severe VP carrying the R59W mutation who was also a compound heterozygote for the HFE mutations his63 to asp (<a href="/entry/235200#0002">235200.0002</a>) and gln127 to his (<a href="/entry/235200#0007">235200.0007</a>). <a href="#6" class="mim-tip-reference" title="de Villiers, J. N. P., Hillermann, R., Loubser, L., Kotze, M. J. <strong>Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria.</strong> Hum. Molec. Genet. 8: 1517-1522, 1999. Note: Erratum: Hum. Molec. Genet. 8: 1817 only, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10401000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10401000</a>] [<a href="https://doi.org/10.1093/hmg/8.8.1517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10401000">De Villiers et al. (1999)</a> concluded that the population screening approach used in their study supported previous data on the involvement of the HFE gene in the porphyria phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10401000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Wiman, A., Harper, P., Floderus, Y. <strong>Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria.</strong> Clin. Genet. 64: 122-130, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12859407/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12859407</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00116.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12859407">Wiman et al. (2003)</a> stated that approximately 80 individuals from 28 apparently unrelated families had been diagnosed with VP in Sweden. Genetic analysis of the PPOX gene in 17 of these families identified 10 different mutations, only 1 of which had previously been reported. None was found in 50 Swedish controls. Mutation analysis in family members revealed 2 adults and 4 children who were silent carriers of the VP trait. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12859407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Borrero Corte, M. J., Jara Rubio, F., Moran Jimenez, M. J., Diaz Diaz, S., Castelbon Fernandez, F. J., Garcia Pastor, I., Enriquez de Salamanca, R., Mendez, M. <strong>Molecular analysis of 19 Spanish patients with mixed porphyrias.</strong> Europ. J. Med. Genet. 62: 103589, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476629</a>] [<a href="https://doi.org/10.1016/j.ejmg.2018.11.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30476629">Borrero Corte et al. (2019)</a> sequenced the PPOX gene in 8 unrelated Spanish patients with variegate porphyria, 4 of whom had only cutaneous photosensitivity, 3 of whom experienced only acute symptoms, and 1 of whom had both. The authors identified heterozygosity for known VP-associated mutations in all patients (see, e.g., <a href="/entry/600923#0006">600923.0006</a>). No genotype/phenotype correlations were observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30476629" 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 25-year-old Spanish man with a 5-year history of cutaneous photosensitivity and a biochemical profile consistent with VP, <a href="#5" class="mim-tip-reference" title="Collantes-Rodriguez, C., de la Varga-Martinez, R., Villegas-Romero, I., Jimenez-Gallo, D., Linares-Barrios, M., Mora-Lopez, F. <strong>Two new mutations in the PPOX gene in a patient with variegate porphyria.</strong> J. Dtsch. Derm. Ges. 18: 381-383, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32247286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32247286</a>] [<a href="https://doi.org/10.1111/ddg.14079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32247286">Collantes-Rodriguez et al. (2020)</a> sequenced the PPOX gene and identified 2 missense mutations in cis, a G41C and W42R substitution, both at highly conserved residues. His similarly affected mother also carried both variants; his unaffected father did not carry either variant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32247286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#28" class="mim-tip-reference" title="von und zu Fraunberg, M., Timonen, K., Mustajoki, P., Kauppinen, R. <strong>Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients.</strong> Europ. J. Hum. Genet. 10: 649-657, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12357337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12357337</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12357337">Von und zu Fraunberg et al. (2002)</a> investigated clinical and biochemical characteristics and genotype-phenotype correlations for 3 common PPOX mutations in Finnish patients with VP identified during a period of 35 years. Of the 103 patients studied, 52% experienced clinical symptoms: 40% had photosensitivity, 27% had acute attacks, and 14% had both manifestations. The proportion of patients with acute attacks decreased from 38% to 14% in patients diagnosed before and after 1980. Of 90 patients genotyped for the common Finnish mutations in PPOX, those with the I12T mutation had no photosensitivity, few acute attacks (8%), and milder biochemical abnormalities. Risk of skin symptoms and acute attacks diminished with normal adult fecal protoporphyrin excretion, but increased with an increased urine excretion of coproporphyrin to the point where all patients with greater than 1,000 nmol/day excretion had skin symptoms, acute attacks, or both. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12357337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Macalpine, I., Hunter, R., Rimington, C. <strong>Porphyria in the royal houses of Stuart, Hanover and Prussia: a follow-up study of George III's illness.</strong> Brit. Med. J. 1: 7-17, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4866084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4866084</a>] [<a href="https://doi.org/10.1136/bmj.1.5583.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4866084">Macalpine et al. (1968)</a> suggested that George III suffered from porphyria and that the disease can be traced back to Mary Queen of Scots, thus starting a spirited controversy. Many authorities do not accept the speculation. Although the malady of George III is indistinguishable retrospectively from acute intermittent porphyria, supposed dermatologic and other manifestations in members of the family suggest that the royal porphyria, if any, was the variegate type. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4866084" 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="Jenkins, T. <strong>The South African malady.</strong> Nature Genet. 13: 7-9, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673106</a>] [<a href="https://doi.org/10.1038/ng0596-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673106">Jenkins (1996)</a> discussed the madness of King George III and also the history of 'the South African malady.' Alan Bennett's highly successful play and film 'The Madness of King George' reawakened debate on whether the sovereign suffered from porphyria. Ida Macalpine and Richard Hunter, who first formulated the retrospective diagnosis (<a href="#20" class="mim-tip-reference" title="Macalpine, I., Hunter, R. <strong>The 'insanity' of King George III: a classic case of porphyria.</strong> Brit. Med. J. 1: 65-71, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5323262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5323262</a>] [<a href="https://doi.org/10.1136/bmj.1.5479.65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5323262">Macalpine and Hunter, 1966</a>), were eminent psychiatrists and were authors of a history of psychiatry (<a href="#13" class="mim-tip-reference" title="Hunter, R., Macalpine, I. <strong>Three Hundred Years of Psychiatry: 1538-1860. A History Presented in Selected English Texts.</strong> London, England: Oxford Univ. Press (pub.) 1963."None>Hunter and Macalpine, 1963</a>). <a href="#30" class="mim-tip-reference" title="Warren, M. J., Jay, M., Hunt, D. M., Elder, G. H., Rohl, J. C. G. <strong>The maddening business of King George III and porphyria.</strong> Trends Biochem. Sci. 21: 229-234, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8744359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8744359</a>]" pmid="8744359">Warren et al. (1996)</a> reviewed the history of the suggested diagnosis and its possible influence on history through the members of the royal family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8673106+8744359+5323262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Hift1997" class="mim-tip-reference" title="Hift, R. J., Meissner, P. N., Corrigall, A. V., Ziman, M. R., Petersen, L. A., Meissner, D. M., Davidson, B. P., Sutherland, J., Dailey, H. A., Kirsch, R. E. <strong>Variegate porphyria in South Africa, 1688-1996: new developments in an old disease.</strong> S. Afr. Med. J. 87: 722-731, 1997.">Hift et al. (1997)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bissbort1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bissbort, S., Hitzeroth, H. W., du Wentzel, D. P., Van den Berg, C. W., Senff, H., Wienker, T. F., Bender, K.
|
|
<strong>Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14.</strong>
|
|
Hum. Genet. 79: 289-290, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3261272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3261272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3261272" 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/BF00366255" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Borrero Corte2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Borrero Corte, M. J., Jara Rubio, F., Moran Jimenez, M. J., Diaz Diaz, S., Castelbon Fernandez, F. J., Garcia Pastor, I., Enriquez de Salamanca, R., Mendez, M.
|
|
<strong>Molecular analysis of 19 Spanish patients with mixed porphyrias.</strong>
|
|
Europ. J. Med. Genet. 62: 103589, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30476629" 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.ejmg.2018.11.023" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Brenner1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brenner, D. A., Bloomer, J. R.
|
|
<strong>The enzymatic defect in variegate porphyria: studies with human cultured skin fibroblasts.</strong>
|
|
New Eng. J. Med. 302: 765-769, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7354807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7354807</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7354807" 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/NEJM198004033021401" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cochrane1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cochrane, A. L., Goldberg, A.
|
|
<strong>A study of faecal porphyrin levels in a large family.</strong>
|
|
Ann. Hum. Genet. 32: 195-208, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5715631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5715631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5715631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1469-1809.1968.tb00064.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Collantes-Rodriguez2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Collantes-Rodriguez, C., de la Varga-Martinez, R., Villegas-Romero, I., Jimenez-Gallo, D., Linares-Barrios, M., Mora-Lopez, F.
|
|
<strong>Two new mutations in the PPOX gene in a patient with variegate porphyria.</strong>
|
|
J. Dtsch. Derm. Ges. 18: 381-383, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32247286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32247286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32247286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/ddg.14079" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="de Villiers1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Villiers, J. N. P., Hillermann, R., Loubser, L., Kotze, M. J.
|
|
<strong>Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria.</strong>
|
|
Hum. Molec. Genet. 8: 1517-1522, 1999. Note: Erratum: Hum. Molec. Genet. 8: 1817 only, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10401000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10401000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10401000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/8.8.1517" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Dean1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dean, G.
|
|
<strong>The Porphyrias. A Story of Inheritance and Environment. (2nd ed.)</strong>
|
|
Philadelphia: J. B. Lippincott (pub.) 1972.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Deybach1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Deybach, J.-C., Puy, H., Robreau, A.-M., Lamoril, J., Da Silva, V., Grandchamp, B., Nordmann, Y.
|
|
<strong>Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria.</strong>
|
|
Hum. Molec. Genet. 5: 407-410, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.3.407" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Frank1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frank, J., Jugert, F. K., Breitkopf, C., Goerz, G., Merk, H. F., Christiano, A. M.
|
|
<strong>Recurrent missense mutation in the protoporphyrinogen oxidase gene underlies variegate porphyria.</strong>
|
|
Am. J. Med. Genet. 79: 22-26, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9738863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9738863</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9738863" 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="10" class="mim-anchor"></a>
|
|
<a id="Fromke1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fromke, V. L., Bossenmaier, I., Cardinal, R., Watson, C. J.
|
|
<strong>Porphyria variegata: study of a large kindred in the United States.</strong>
|
|
Am. J. Med. 65: 80-88, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/686004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">686004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=686004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9343(78)90696-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Hamnstrom1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamnstrom, B., Haeger-Aronsen, B., Waldenstrom, J., Hysing, B., Molander, J.
|
|
<strong>Three Swedish families with porphyria variegata.</strong>
|
|
Brit. Med. J. 4: 449-453, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6055732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6055732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6055732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.4.5577.449" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Hift1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hift, R. J., Meissner, P. N., Corrigall, A. V., Ziman, M. R., Petersen, L. A., Meissner, D. M., Davidson, B. P., Sutherland, J., Dailey, H. A., Kirsch, R. E.
|
|
<strong>Variegate porphyria in South Africa, 1688-1996: new developments in an old disease.</strong>
|
|
S. Afr. Med. J. 87: 722-731, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9254745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9254745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9254745" 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="13" class="mim-anchor"></a>
|
|
<a id="Hunter1963" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hunter, R., Macalpine, I.
|
|
<strong>Three Hundred Years of Psychiatry: 1538-1860. A History Presented in Selected English Texts.</strong>
|
|
London, England: Oxford Univ. Press (pub.) 1963.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Husquinet1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Husquinet, H., Noirfalise, A., Parent, M.-T.
|
|
<strong>Porphyria variegata: etude d'une grande famille.</strong>
|
|
J. Genet. Hum. 26: 367-383, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/752067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">752067</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=752067" 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="15" class="mim-anchor"></a>
|
|
<a id="Jenkins1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jenkins, T.
|
|
<strong>Medical genetics in South Africa.</strong>
|
|
J. Med. Genet. 27: 760-779, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2074562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2074562</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2074562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.27.12.760" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Jenkins1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jenkins, T.
|
|
<strong>The South African malady.</strong>
|
|
Nature Genet. 13: 7-9, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0596-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Kushner1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kushner, J. P.
|
|
<strong>Laboratory diagnosis of the porphyrias. (Editorial)</strong>
|
|
New Eng. J. Med. 324: 1432-1434, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2020301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2020301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2020301" 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/NEJM199105163242010" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Logan1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Logan, G. M., Weimer, M. K., Ellefson, M., Pierach, C. A., Bloomer, J. R.
|
|
<strong>Bile porphyrin analysis in the evaluation of variegate porphyria.</strong>
|
|
New Eng. J. Med. 324: 1408-1411, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2020296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2020296</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2020296" 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/NEJM199105163242005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Macalpine1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Macalpine, I., Hunter, R., Rimington, C.
|
|
<strong>Porphyria in the royal houses of Stuart, Hanover and Prussia: a follow-up study of George III's illness.</strong>
|
|
Brit. Med. J. 1: 7-17, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4866084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4866084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4866084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.1.5583.7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Macalpine1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Macalpine, I., Hunter, R.
|
|
<strong>The 'insanity' of King George III: a classic case of porphyria.</strong>
|
|
Brit. Med. J. 1: 65-71, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5323262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5323262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5323262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.1.5479.65" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Meissner1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meissner, P. N., Dailey, T. A., Hift, R. J., Ziman, M., Corrigall, A. V., Roberts, A. G., Meissner, D. M., Kirsch, R. E., Dailey, H. A.
|
|
<strong>A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria.</strong>
|
|
Nature Genet. 13: 95-97, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0596-95" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Meyer1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer, U. A., Schmid, R.
|
|
<strong>The porphyrias. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.): The Metabolic Basis of Inherited Disease. (4th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1978. Pp. 1166-1220.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Mustajoki1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mustajoki, P.
|
|
<strong>Variegate porphyria.</strong>
|
|
Ann. Intern. Med. 89: 238-244, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/677592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">677592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=677592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-89-2-238" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Mustajoki1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mustajoki, P.
|
|
<strong>Variegate porphyria: twelve years' experience in Finland.</strong>
|
|
Quart. J. Med. 49: 191-203, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7433635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7433635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7433635" 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="Roberts1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roberts, A. G., Whatley, S. D., Daniels, J., Holmans, P., Fenton, I., Owen, M. J., Thompson, P., Long, C., Elder, G. H.
|
|
<strong>Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23.</strong>
|
|
Hum. Molec. Genet. 4: 2387-2390, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.12.2387" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Stine1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stine, O. C., Smith, K. D.
|
|
<strong>The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.</strong>
|
|
Am. J. Hum. Genet. 46: 452-458, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2137963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2137963</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2137963" 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="27" class="mim-anchor"></a>
|
|
<a id="Taketani1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taketani, S., Inazawa, J., Abe, T., Furukawa, T., Kohno, H., Tokunaga, R., Nishimura, K., Inokuchi, H.
|
|
<strong>The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1.</strong>
|
|
Genomics 29: 698-703, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8575762" 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.1995.9949" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="von und zu Fraunberg2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
von und zu Fraunberg, M., Timonen, K., Mustajoki, P., Kauppinen, R.
|
|
<strong>Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients.</strong>
|
|
Europ. J. Hum. Genet. 10: 649-657, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12357337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12357337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12357337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200860" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Warnich1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Warnich, L., Kotze, M. J., Groenewald, I. M., Groenewald, J. Z., van Brakel, M. G., van Heerden, C. J., de Villiers, J. N. P., van de Ven, W. J. M., Schoenmakers, E. F. P. M., Taketani, S., Retief, A. E.
|
|
<strong>Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria.</strong>
|
|
Hum. Molec. Genet. 5: 981-984, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.7.981" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Warren1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Warren, M. J., Jay, M., Hunt, D. M., Elder, G. H., Rohl, J. C. G.
|
|
<strong>The maddening business of King George III and porphyria.</strong>
|
|
Trends Biochem. Sci. 21: 229-234, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8744359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8744359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8744359" 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="Wiman2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wiman, A., Harper, P., Floderus, Y.
|
|
<strong>Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria.</strong>
|
|
Clin. Genet. 64: 122-130, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12859407/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12859407</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12859407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2003.00116.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 09/11/2023
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 08/25/2023<br>Marla J. F. O'Neill - updated : 08/25/2023<br>Cassandra L. Kniffin - updated : 6/3/2004<br>Natalie E. Krasikov - updated : 6/3/2004<br>Victor A. McKusick - updated : 10/6/1999<br>Ada Hamosh - updated : 8/9/1999<br>Moyra Smith - updated : 8/21/1996
|
|
</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 : 6/2/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/11/2023
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 08/25/2023<br>alopez : 08/25/2023<br>carol : 08/23/2023<br>carol : 03/01/2022<br>carol : 05/29/2019<br>carol : 08/26/2016<br>carol : 07/09/2016<br>carol : 7/9/2016<br>carol : 9/16/2013<br>carol : 4/12/2013<br>carol : 8/10/2010<br>carol : 8/6/2010<br>carol : 8/5/2010<br>carol : 2/25/2009<br>terry : 2/6/2009<br>carol : 6/7/2004<br>ckniffin : 6/3/2004<br>carol : 6/3/2004<br>mgross : 10/22/1999<br>mgross : 10/22/1999<br>terry : 10/6/1999<br>alopez : 8/20/1999<br>alopez : 8/17/1999<br>terry : 8/9/1999<br>terry : 10/1/1998<br>carol : 7/9/1998<br>alopez : 8/4/1997<br>alopez : 7/30/1997<br>jenny : 7/9/1997<br>alopez : 6/2/1997<br>jamie : 11/22/1996<br>mark : 11/11/1996<br>terry : 10/31/1996<br>mark : 8/21/1996<br>terry : 8/20/1996<br>marlene : 8/16/1996<br>mark : 4/30/1996<br>mark : 4/30/1996<br>terry : 4/30/1996<br>mark : 4/17/1996<br>terry : 4/10/1996<br>terry : 11/7/1995<br>mark : 5/22/1995<br>mimadm : 2/25/1995<br>carol : 11/3/1994<br>davew : 8/19/1994<br>warfield : 3/4/1994
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>#</strong> 176200
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
VARIEGATE PORPHYRIA; VP
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
PORPHYRIA VARIEGATA<br />
|
|
PORPHYRIA, SOUTH AFRICAN TYPE<br />
|
|
PROTOPORPHYRINOGEN OXIDASE DEFICIENCY<br />
|
|
PPOX DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 58275005;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 79473;
|
|
|
|
|
|
<strong>DO:</strong> 4346;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
1q23.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Variegate porphyria
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
176200
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
PPOX
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600923
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that variegate porphyria (VP) is caused by heterozygous mutation in the gene encoding protoporphyrinogen oxidase (PPOX; 600923) on chromosome 1q23.</p><p>Biallelic mutation in the PPOX gene causes a childhood-onset form of variegate porphyria (VPCO; 620483).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Variegate porphyria (VP) is characterized by cutaneous manifestations, including increased photosensitivity, blistering, skin fragility with chronic scarring of sun-exposed areas, and postinflammatory hyperpigmentation. Acute exacerbations of VP include abdominal pain, the passage of dark urine, and neuropsychiatric symptoms that characterize the acute hepatic porphyrias, such as bulbar paralysis, quadriplegia, motor neuropathy, and weakness of the limbs. VP is inherited as an autosomal dominant trait with incomplete penetrance. Clinical manifestations do not usually present before puberty, and PPOX activity is decreased by about 50% (summary by Frank et al., 1998). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Adults with variegate porphyria show a variable picture of skin symptoms, including hyperpigmentation and hypertrichosis, associated with acute attacks like those of acute intermittent porphyria (176000). Attacks may be protracted and followed by prolonged disability. Attacks are often drug-induced and show the classic neuropathic symptoms and signs, such as abdominal pain, constipation, tachycardia and hypertension, and muscular paralysis and sensory disturbances; disorientation and frank psychosis may be conspicuous features. The condition is characterized by elevated fecal levels of protoporphyrin and coproporphyrin at all times, with increased urine porphyrins at times, and an increase in urinary levels of the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) during the acute attack (Dean, 1972; Mustajoki, 1978; Meyer and Schmid, 1978). Iron overload is a well-established precipitating or aggravating factor in porphyria variegata. </p><p>Frank et al. (1998) reported 2 unrelated patients with variegate porphyria and mutation in the PPOX gene. Proband 1 was a 57-year-old woman of German ancestry who developed a life-threatening acute porphyric attack with paralysis at around 30 years of age. At that time the diagnosis of acute intermittent porphyria was rendered on the basis of clinical and biochemical findings. Thereafter she experienced recurrent colicky abdominal pain, vomiting, and mental confusion. Upon sun exposure, small blisters developed on the forearms and the back of the hands that left chronic hyperpigmented scars. The diagnosis of variegate porphyria was made on the basis of the cutaneous symptoms and porphyrin analysis of the feces. Proband 2 was a 38-year-old woman of Armenian and North American ancestry who was diagnosed with variegate porphyria on the basis of clinical and biochemical findings; no clinical details were provided. </p><p>Collantes-Rodriguez et al. (2020) reported a 25-year-old Spanish man with a 5-year history of blistering skin lesions on the backs of his hands, associated with hyperpigmentation and hypertrichosis and exacerbation in spring and summer. He had no systemic symptoms. There was a maternal family history of similar lesions without associated systemic symptoms. Biochemical analysis showed elevated uroporphyrin and the presence of coproporphyrin and protoporphyrin in the proband's feces. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The basic defect appears to be reduction in the activity of the enzyme protoporphyrinogen oxidase to approximately 50% of the normal level as determined in skin fibroblasts (Brenner and Bloomer, 1980) and presumably in other tissues, especially liver. This enzymopathy is unusual in being the effect of a single gene dose, rather than requiring a double dose for its expression. Several other genetic porphyrias share this effect; see 121300, 176000, and 176100. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Logan et al. (1991) noted that biochemical confirmation of the diagnosis of variegate porphyria can be difficult, particularly in patients without neurologic dysfunction at the time of testing. Levels of porphyrin in the stool may be normal because food and bacterial metabolism in the intestine contribute to the porphyrin content of the feces and may obscure the differences in levels between normal and affected persons. To overcome this shortcoming, Logan et al. (1991) measured porphyrin levels in the bile and found considerably greater differences in bile levels than in fecal levels in patients and normals. Kushner (1991) reviewed the laboratory diagnosis of the porphyrias. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Management of porphyria consists primarily of avoidance of porphyrinogenic agents and protection for photosensitive skin (Kushner, 1991). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Cochrane and Goldberg (1968) reported studies of an extensive kindred of which the first author was a member. Children and asymptomatic adults showed the chemical features without manifest disease, but allowed the demonstration that porphyria variegata segregates is an autosomal dominant trait, with manifestation in about one half of affected adults (Cochrane and Goldberg, 1968; Dean, 1972; Hamnstrom et al., 1967; Fromke et al., 1978; Husquinet et al., 1978). </p><p>VP is usually inherited as an autosomal dominant trait with incomplete penetrance (Frank et al., 1998). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Porphyria variegata was observed in 3 families in Sweden by Hamnstrom et al. (1967). No genealogic connection with any of the 600 known cases of acute intermittent porphyria could be shown. </p><p>Dean (1972) described in an engaging manner his studies of porphyria in South Africa and comparative studies in Sweden, Holland, Turkey, and elsewhere. The high frequency of the gene for porphyria variegata in South Africa is a cardinal example of founder effect. Dean (1972) estimated that about 8,000 persons in South Africa were suffering from porphyria inherited from either Gerrit Jansz, a Dutch settler in the Cape, or his wife, Ariaantje Jacobs, who was 1 of 8 sent from an orphanage in Rotterdam to provide wives for Dutch settlers in the Cape. He estimated, furthermore, that 1 million of 3 million whites are descendants of 40 original settlers and their wives, a 12,000-fold increase. Stine and Smith (1990) calculated a coefficient of selection between 0.07 and 0.02 for the porphyria variegata gene in the Afrikaner population of South Africa. Jenkins (1990) gave a comprehensive review of medical genetics in South Africa; porphyria variegata was included in a listing of inherited conditions of unusual prevalence among some southern African populations. (See 600923.0003 for the probable founder gene defect associated causally with VP in South Africa.) </p><p>Porphyria variegata is also frequent in Finland (Mustajoki, 1980), where prevalence was estimated to be 1.3 per 100,000. Of 57 patients in 9 families, 18 had had acute attacks. During an average of 5.7 years' follow-up, only 2 of 48 patients had symptoms, which were temporary and acute. The longevity of gene carriers did not differ from that of the general population. Skin fragility occurred in 45% of patients and was usually mild. Mustajoki (1980) concluded that variegate porphyria might be commoner than suspected, noting that only half of patients in temperate and cold climates have skin symptoms, the risk of developing an acute attack is low, and some adult patients excrete normal or only slightly abnormal amounts of porphyrin. Of 57 patients in 9 families, 18 had had acute attacks, but the longevity of gene carriers did not differ from that of the general population. Skin fragility was usually mild. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Bissbort et al. (1988) demonstrated linkage between VP and alpha-1-antitrypsin (107400); the maximum lod score from male meioses was 4.33 at theta = 0.04, and from both sexes combined, 3.56 at theta = 0.12. In pedigrees triply informative for VP, PI and the Gm polymorphism, VP and PI cosegregated separately from Gm. These findings argued in favor of either gene order VP--PI--IGHC or PI--VP--IGHC. </p><p>Taketani et al. (1995) showed by Southern blotting of human genomic DNA that there is a single copy of the PPOX gene, and by fluorescence in situ hybridization they mapped the gene to 1q22 (see also 600923). The reason for the discrepancy between linkage mapping of variegate porphyria to chromosome 14 by Bissbort et al. (1988) and this location of the gene by fluorescence in situ hybridization is unexplained; however, Taketani et al. (1995) suggested that it is possible that an additional gene product on chromosome 14 may interact with PPOX protein to maintain the normal enzyme activity or to affect expression of the PPOX gene (thus accounting for the findings of Bissbort et al. (1988) referred to earlier). </p><p>Roberts et al. (1995) likewise mapped the PPOX gene to chromosome 1 (1q23) and showed that the clinical disorder variegate porphyria is linked to microsatellite and other markers in the region 1q21-q23. They concluded that the evidence spoke against locus heterogeneity in VP. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Deybach et al. (1996) investigated the molecular defect responsible for VP by sequencing the coding portions of the PPOX gene in 4 patients in 3 unrelated families of French Caucasian origin. In 1 patient, insertion of G at position 1022 of the cDNA produced a frameshift resulting in a premature stop codon (600923.0001). In 3 other patients from 2 unrelated families, they found a missense mutation leading to substitution of arginine for glycine (G232R) in exon 7 (600923.0002). In 1 of the latter families, consisting of 14 members over 3 generations, they demonstrated the cosegregation of the G232R mutation with deficient PPOX activity. This was the first report of mutations in patients with VP and supported the conclusion that PPOX gene defects cause variegate porphyria. </p><p>Meissner et al. (1996) described an arg59-to-trp (R59W) mutation in the PPOX gene (600923.0003) in 43 of 45 patients with VP from 26 of 27 South African families investigated, but not in 34 unaffected relatives or 9 unrelated British patients with protoporphyrinogen oxidase deficiency. Since at least one of these families could be shown to be descended from the founder of South African VP, this defect may represent the founder gene defect associated causally with VP in South Africa. </p><p>Warnich et al. (1996) identified the R59W mutation in 15 of 17 South African patients with variegate porphyria. This mutation was shown to create a StyI restriction site and was found to be associated with C(26)-C(150), 1 of 4 potential haplotypes defined by 2 polymorphisms in exon 1 of the PPOX gene. Warnich et al. (1996) reported that these data supported the founder hypothesis for variegate porphyria in South Africa. In 1 of 17 patients there was an exon 2 mutation (H20P; 600923.0005). This mutation was associated with the same exon 1 polymorphism haplotype as the R59W mutation. An exon 6 mutation, R168C (600923.0004), was identified in 1 patient; this mutation abolished a DsaI restriction site in genomic DNA of affected individuals and was shown to be associated with a different haplotype for the exon 1 polymorphism, A(26)-C(150). </p><p>In 2 unrelated women with variegate porphyria, Frank et al. (1998) analyzed exon 6 of the PPOX gene and identified heterozygosity for the same missense mutation (R168H; 600923.0006). Segregation analysis in the family of proband 1 revealed that her unaffected son also carried the R168H variant, indicating incomplete penetrance; relatives of proband 2 were unavailable for study. The mutation was not found in 50 unrelated controls. </p><p>De Villiers et al. (1999) identified a South African patient with severe VP carrying the R59W mutation who was also a compound heterozygote for the HFE mutations his63 to asp (235200.0002) and gln127 to his (235200.0007). De Villiers et al. (1999) concluded that the population screening approach used in their study supported previous data on the involvement of the HFE gene in the porphyria phenotype. </p><p>Wiman et al. (2003) stated that approximately 80 individuals from 28 apparently unrelated families had been diagnosed with VP in Sweden. Genetic analysis of the PPOX gene in 17 of these families identified 10 different mutations, only 1 of which had previously been reported. None was found in 50 Swedish controls. Mutation analysis in family members revealed 2 adults and 4 children who were silent carriers of the VP trait. </p><p>Borrero Corte et al. (2019) sequenced the PPOX gene in 8 unrelated Spanish patients with variegate porphyria, 4 of whom had only cutaneous photosensitivity, 3 of whom experienced only acute symptoms, and 1 of whom had both. The authors identified heterozygosity for known VP-associated mutations in all patients (see, e.g., 600923.0006). No genotype/phenotype correlations were observed. </p><p>In a 25-year-old Spanish man with a 5-year history of cutaneous photosensitivity and a biochemical profile consistent with VP, Collantes-Rodriguez et al. (2020) sequenced the PPOX gene and identified 2 missense mutations in cis, a G41C and W42R substitution, both at highly conserved residues. His similarly affected mother also carried both variants; his unaffected father did not carry either variant. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Von und zu Fraunberg et al. (2002) investigated clinical and biochemical characteristics and genotype-phenotype correlations for 3 common PPOX mutations in Finnish patients with VP identified during a period of 35 years. Of the 103 patients studied, 52% experienced clinical symptoms: 40% had photosensitivity, 27% had acute attacks, and 14% had both manifestations. The proportion of patients with acute attacks decreased from 38% to 14% in patients diagnosed before and after 1980. Of 90 patients genotyped for the common Finnish mutations in PPOX, those with the I12T mutation had no photosensitivity, few acute attacks (8%), and milder biochemical abnormalities. Risk of skin symptoms and acute attacks diminished with normal adult fecal protoporphyrin excretion, but increased with an increased urine excretion of coproporphyrin to the point where all patients with greater than 1,000 nmol/day excretion had skin symptoms, acute attacks, or both. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Macalpine et al. (1968) suggested that George III suffered from porphyria and that the disease can be traced back to Mary Queen of Scots, thus starting a spirited controversy. Many authorities do not accept the speculation. Although the malady of George III is indistinguishable retrospectively from acute intermittent porphyria, supposed dermatologic and other manifestations in members of the family suggest that the royal porphyria, if any, was the variegate type. </p><p>Jenkins (1996) discussed the madness of King George III and also the history of 'the South African malady.' Alan Bennett's highly successful play and film 'The Madness of King George' reawakened debate on whether the sovereign suffered from porphyria. Ida Macalpine and Richard Hunter, who first formulated the retrospective diagnosis (Macalpine and Hunter, 1966), were eminent psychiatrists and were authors of a history of psychiatry (Hunter and Macalpine, 1963). Warren et al. (1996) reviewed the history of the suggested diagnosis and its possible influence on history through the members of the royal family. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Hift et al. (1997)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bissbort, S., Hitzeroth, H. W., du Wentzel, D. P., Van den Berg, C. W., Senff, H., Wienker, T. F., Bender, K.
|
|
<strong>Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14.</strong>
|
|
Hum. Genet. 79: 289-290, 1988.
|
|
|
|
|
|
[PubMed: 3261272]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00366255]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Borrero Corte, M. J., Jara Rubio, F., Moran Jimenez, M. J., Diaz Diaz, S., Castelbon Fernandez, F. J., Garcia Pastor, I., Enriquez de Salamanca, R., Mendez, M.
|
|
<strong>Molecular analysis of 19 Spanish patients with mixed porphyrias.</strong>
|
|
Europ. J. Med. Genet. 62: 103589, 2019.
|
|
|
|
|
|
[PubMed: 30476629]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ejmg.2018.11.023]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brenner, D. A., Bloomer, J. R.
|
|
<strong>The enzymatic defect in variegate porphyria: studies with human cultured skin fibroblasts.</strong>
|
|
New Eng. J. Med. 302: 765-769, 1980.
|
|
|
|
|
|
[PubMed: 7354807]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198004033021401]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cochrane, A. L., Goldberg, A.
|
|
<strong>A study of faecal porphyrin levels in a large family.</strong>
|
|
Ann. Hum. Genet. 32: 195-208, 1968.
|
|
|
|
|
|
[PubMed: 5715631]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1968.tb00064.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Collantes-Rodriguez, C., de la Varga-Martinez, R., Villegas-Romero, I., Jimenez-Gallo, D., Linares-Barrios, M., Mora-Lopez, F.
|
|
<strong>Two new mutations in the PPOX gene in a patient with variegate porphyria.</strong>
|
|
J. Dtsch. Derm. Ges. 18: 381-383, 2020.
|
|
|
|
|
|
[PubMed: 32247286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/ddg.14079]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Villiers, J. N. P., Hillermann, R., Loubser, L., Kotze, M. J.
|
|
<strong>Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria.</strong>
|
|
Hum. Molec. Genet. 8: 1517-1522, 1999. Note: Erratum: Hum. Molec. Genet. 8: 1817 only, 1999.
|
|
|
|
|
|
[PubMed: 10401000]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.8.1517]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dean, G.
|
|
<strong>The Porphyrias. A Story of Inheritance and Environment. (2nd ed.)</strong>
|
|
Philadelphia: J. B. Lippincott (pub.) 1972.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deybach, J.-C., Puy, H., Robreau, A.-M., Lamoril, J., Da Silva, V., Grandchamp, B., Nordmann, Y.
|
|
<strong>Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria.</strong>
|
|
Hum. Molec. Genet. 5: 407-410, 1996.
|
|
|
|
|
|
[PubMed: 8852667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.3.407]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frank, J., Jugert, F. K., Breitkopf, C., Goerz, G., Merk, H. F., Christiano, A. M.
|
|
<strong>Recurrent missense mutation in the protoporphyrinogen oxidase gene underlies variegate porphyria.</strong>
|
|
Am. J. Med. Genet. 79: 22-26, 1998.
|
|
|
|
|
|
[PubMed: 9738863]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fromke, V. L., Bossenmaier, I., Cardinal, R., Watson, C. J.
|
|
<strong>Porphyria variegata: study of a large kindred in the United States.</strong>
|
|
Am. J. Med. 65: 80-88, 1978.
|
|
|
|
|
|
[PubMed: 686004]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(78)90696-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamnstrom, B., Haeger-Aronsen, B., Waldenstrom, J., Hysing, B., Molander, J.
|
|
<strong>Three Swedish families with porphyria variegata.</strong>
|
|
Brit. Med. J. 4: 449-453, 1967.
|
|
|
|
|
|
[PubMed: 6055732]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.4.5577.449]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hift, R. J., Meissner, P. N., Corrigall, A. V., Ziman, M. R., Petersen, L. A., Meissner, D. M., Davidson, B. P., Sutherland, J., Dailey, H. A., Kirsch, R. E.
|
|
<strong>Variegate porphyria in South Africa, 1688-1996: new developments in an old disease.</strong>
|
|
S. Afr. Med. J. 87: 722-731, 1997.
|
|
|
|
|
|
[PubMed: 9254745]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hunter, R., Macalpine, I.
|
|
<strong>Three Hundred Years of Psychiatry: 1538-1860. A History Presented in Selected English Texts.</strong>
|
|
London, England: Oxford Univ. Press (pub.) 1963.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Husquinet, H., Noirfalise, A., Parent, M.-T.
|
|
<strong>Porphyria variegata: etude d'une grande famille.</strong>
|
|
J. Genet. Hum. 26: 367-383, 1978.
|
|
|
|
|
|
[PubMed: 752067]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jenkins, T.
|
|
<strong>Medical genetics in South Africa.</strong>
|
|
J. Med. Genet. 27: 760-779, 1990.
|
|
|
|
|
|
[PubMed: 2074562]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.27.12.760]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jenkins, T.
|
|
<strong>The South African malady.</strong>
|
|
Nature Genet. 13: 7-9, 1996.
|
|
|
|
|
|
[PubMed: 8673106]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0596-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kushner, J. P.
|
|
<strong>Laboratory diagnosis of the porphyrias. (Editorial)</strong>
|
|
New Eng. J. Med. 324: 1432-1434, 1991.
|
|
|
|
|
|
[PubMed: 2020301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199105163242010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Logan, G. M., Weimer, M. K., Ellefson, M., Pierach, C. A., Bloomer, J. R.
|
|
<strong>Bile porphyrin analysis in the evaluation of variegate porphyria.</strong>
|
|
New Eng. J. Med. 324: 1408-1411, 1991.
|
|
|
|
|
|
[PubMed: 2020296]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199105163242005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Macalpine, I., Hunter, R., Rimington, C.
|
|
<strong>Porphyria in the royal houses of Stuart, Hanover and Prussia: a follow-up study of George III's illness.</strong>
|
|
Brit. Med. J. 1: 7-17, 1968.
|
|
|
|
|
|
[PubMed: 4866084]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.1.5583.7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Macalpine, I., Hunter, R.
|
|
<strong>The 'insanity' of King George III: a classic case of porphyria.</strong>
|
|
Brit. Med. J. 1: 65-71, 1966.
|
|
|
|
|
|
[PubMed: 5323262]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.1.5479.65]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meissner, P. N., Dailey, T. A., Hift, R. J., Ziman, M., Corrigall, A. V., Roberts, A. G., Meissner, D. M., Kirsch, R. E., Dailey, H. A.
|
|
<strong>A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria.</strong>
|
|
Nature Genet. 13: 95-97, 1996.
|
|
|
|
|
|
[PubMed: 8673113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0596-95]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer, U. A., Schmid, R.
|
|
<strong>The porphyrias. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.): The Metabolic Basis of Inherited Disease. (4th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1978. Pp. 1166-1220.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mustajoki, P.
|
|
<strong>Variegate porphyria.</strong>
|
|
Ann. Intern. Med. 89: 238-244, 1978.
|
|
|
|
|
|
[PubMed: 677592]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-89-2-238]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mustajoki, P.
|
|
<strong>Variegate porphyria: twelve years' experience in Finland.</strong>
|
|
Quart. J. Med. 49: 191-203, 1980.
|
|
|
|
|
|
[PubMed: 7433635]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roberts, A. G., Whatley, S. D., Daniels, J., Holmans, P., Fenton, I., Owen, M. J., Thompson, P., Long, C., Elder, G. H.
|
|
<strong>Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23.</strong>
|
|
Hum. Molec. Genet. 4: 2387-2390, 1995.
|
|
|
|
|
|
[PubMed: 8634714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.12.2387]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stine, O. C., Smith, K. D.
|
|
<strong>The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.</strong>
|
|
Am. J. Hum. Genet. 46: 452-458, 1990.
|
|
|
|
|
|
[PubMed: 2137963]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taketani, S., Inazawa, J., Abe, T., Furukawa, T., Kohno, H., Tokunaga, R., Nishimura, K., Inokuchi, H.
|
|
<strong>The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1.</strong>
|
|
Genomics 29: 698-703, 1995.
|
|
|
|
|
|
[PubMed: 8575762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.9949]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
von und zu Fraunberg, M., Timonen, K., Mustajoki, P., Kauppinen, R.
|
|
<strong>Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients.</strong>
|
|
Europ. J. Hum. Genet. 10: 649-657, 2002.
|
|
|
|
|
|
[PubMed: 12357337]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200860]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warnich, L., Kotze, M. J., Groenewald, I. M., Groenewald, J. Z., van Brakel, M. G., van Heerden, C. J., de Villiers, J. N. P., van de Ven, W. J. M., Schoenmakers, E. F. P. M., Taketani, S., Retief, A. E.
|
|
<strong>Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria.</strong>
|
|
Hum. Molec. Genet. 5: 981-984, 1996.
|
|
|
|
|
|
[PubMed: 8817334]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.7.981]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warren, M. J., Jay, M., Hunt, D. M., Elder, G. H., Rohl, J. C. G.
|
|
<strong>The maddening business of King George III and porphyria.</strong>
|
|
Trends Biochem. Sci. 21: 229-234, 1996.
|
|
|
|
|
|
[PubMed: 8744359]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wiman, A., Harper, P., Floderus, Y.
|
|
<strong>Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria.</strong>
|
|
Clin. Genet. 64: 122-130, 2003.
|
|
|
|
|
|
[PubMed: 12859407]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00116.x]
|
|
|
|
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 09/11/2023<br>Marla J. F. O'Neill - updated : 08/25/2023<br>Marla J. F. O'Neill - updated : 08/25/2023<br>Cassandra L. Kniffin - updated : 6/3/2004<br>Natalie E. Krasikov - updated : 6/3/2004<br>Victor A. McKusick - updated : 10/6/1999<br>Ada Hamosh - updated : 8/9/1999<br>Moyra Smith - updated : 8/21/1996
|
|
</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 : 6/2/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/11/2023<br>alopez : 08/25/2023<br>alopez : 08/25/2023<br>carol : 08/23/2023<br>carol : 03/01/2022<br>carol : 05/29/2019<br>carol : 08/26/2016<br>carol : 07/09/2016<br>carol : 7/9/2016<br>carol : 9/16/2013<br>carol : 4/12/2013<br>carol : 8/10/2010<br>carol : 8/6/2010<br>carol : 8/5/2010<br>carol : 2/25/2009<br>terry : 2/6/2009<br>carol : 6/7/2004<br>ckniffin : 6/3/2004<br>carol : 6/3/2004<br>mgross : 10/22/1999<br>mgross : 10/22/1999<br>terry : 10/6/1999<br>alopez : 8/20/1999<br>alopez : 8/17/1999<br>terry : 8/9/1999<br>terry : 10/1/1998<br>carol : 7/9/1998<br>alopez : 8/4/1997<br>alopez : 7/30/1997<br>jenny : 7/9/1997<br>alopez : 6/2/1997<br>jamie : 11/22/1996<br>mark : 11/11/1996<br>terry : 10/31/1996<br>mark : 8/21/1996<br>terry : 8/20/1996<br>marlene : 8/16/1996<br>mark : 4/30/1996<br>mark : 4/30/1996<br>terry : 4/30/1996<br>mark : 4/17/1996<br>terry : 4/10/1996<br>terry : 11/7/1995<br>mark : 5/22/1995<br>mimadm : 2/25/1995<br>carol : 11/3/1994<br>davew : 8/19/1994<br>warfield : 3/4/1994
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|