11838 lines
1.1 MiB
11838 lines
1.1 MiB
|
|
|
|
|
|
|
|
|
|
<!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
|
|
|
|
- *107400 - SERPIN PEPTIDASE INHIBITOR, CLADE A, MEMBER 1; SERPINA1
|
|
|
|
|
|
- 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=107400"><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">*107400</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#nomenclature">Nomenclature</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="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/107400">Table View</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="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000197249;t=ENST00000393087" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=5265" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=107400" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000197249;t=ENST00000393087" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000295,NM_001002235,NM_001002236,NM_001127700,NM_001127701,NM_001127702,NM_001127703,NM_001127704,NM_001127705,NM_001127706,NM_001127707,XM_017021370,XM_047431478,XM_047431479" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000295" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=107400" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=02463&isoform_id=02463_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/SERPINA1" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/24438,24442,28637,28966,177816,177822,177823,177824,177827,177829,177831,177836,825632,1703025,6524687,7770183,10043419,15080499,15990507,28071066,28193128,28193184,28207863,30142138,50363217,50363219,50363221,54695780,76364257,84784317,110350939,119601976,119601977,119601978,119601979,119601980,119601981,119601982,149786561,151302818,152207506,152207508,171474646,189055021,189163528,189163530,189163532,189163534,189163536,189163538,189163540,189163542,226427752,238695886,308219714,317040114,957949975,957949978,1034587302,1129799321,1129799323,1130712380,1130712382,2217297712,2217297714,2314654499,2462490393,2462490395,2462540572,2462540574,2462540576" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/P01009" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=5265" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000197249;t=ENST00000393087" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERPINA1" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=SERPINA1" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+5265" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/SERPINA1" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:5265" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/5265" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr14&hgg_gene=ENST00000393087.9&hgg_start=94376747&hgg_end=94390635&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:8941" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/serpina1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=107400[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=107400[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000197249" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=SERPINA1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=SERPINA1" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SERPINA1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
|
|
<div id="mimLocusSpecificDBsFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/SERPINA1" title="CCHMC - Human Genetics Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC - Human Genetics Mut…</a></div><div style="margin-left: 0.5em;"><a href="http://www.goldenhelix.org/a1atvar/" title="A1ATVar: A1-antitrypsin database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">A1ATVar: A1-antitrypsin da…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SERPINA1&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA35509" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:8941" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0031973.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/search?q=MGI:891967 MGI:891968 MGI:891969 MGI:891970 MGI:891971" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/SERPINA1#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/batch/summary?idType=MGI&ids=MGI:891967 MGI:891968 MGI:891969 MGI:891970 MGI:891971" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/5265/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA000032/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=5265" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00005649;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030131-1421" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="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:107400" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5265" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=SERPINA1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
107400
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SERPIN PEPTIDASE INHIBITOR, CLADE A, MEMBER 1; SERPINA1
|
|
|
|
</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">
|
|
ALPHA-1-ANTITRYPSIN; AAT<br />
|
|
PROTEASE INHIBITOR 1; PI<br />
|
|
PI1<br />
|
|
ANTI-ELASTASE<br />
|
|
ANTITRYPSIN
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SERPINA1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SERPINA1</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/14/492?start=-3&limit=10&highlight=492">14q32.13</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:94376747-94390635&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">14:94,376,747-94,390,635</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/492?start=-3&limit=10&highlight=492">
|
|
14q32.13
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Emphysema due to AAT deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613490"> 613490 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Emphysema-cirrhosis, due to AAT deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613490"> 613490 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hemorrhagic diathesis due to antithrombin Pittsburgh
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613490"> 613490 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/107400" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/107400" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The SERPINA1 gene encodes alpha-1-antitrypsin (AAT), also known as protease inhibitor (PI), a major plasma serine protease inhibitor. AAT complexes predominantly with elastase, but also with trypsin, chymotrypsin, thrombin, and bacterial proteases. The most important inhibitory action of AAT is that against neutrophil elastase (ELANE, or HLE; <a href="/entry/130130">130130</a>), a protease that degrades elastin of the alveolar walls as well as other structural proteins of a variety of tissues (review by <a href="#33" class="mim-tip-reference" title="Cox, D. W. <strong>Alpha-1-antitrypsin. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. IV. (8th ed.)</strong> New York: McGraw-Hill 2001. Pp. 5559-5584."None>Cox, 2001</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#91" class="mim-tip-reference" title="Kurachi, K., Chandra, T., Degen, S. J. F., White, T. T., Marchioro, T. L., Woo, S. L. C., Davie, E. W. <strong>Cloning and sequence of cDNA coding for alpha-1-antitrypsin.</strong> Proc. Nat. Acad. Sci. 78: 6826-6830, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7031661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7031661</a>] [<a href="https://doi.org/10.1073/pnas.78.11.6826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7031661">Kurachi et al. (1981)</a> cloned a nearly full-length baboon AAT cDNA (approximately 1,352 bp) and a partial human AAT cDNA (approximately 306 bp). They found more than 96% homology between the cDNA and predicted amino acid sequences of AAT in the 2 species. Comparison of baboon AAT, human antithrombin III (<a href="/entry/107300">107300</a>), and chicken ovalbumin indicated about 30% homology of amino acid sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7031661" 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="#98" class="mim-tip-reference" title="Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W., Kurachi, K. <strong>Complete sequence of the cDNA for human alpha-1-antitrypsin and the gene for the S variant.</strong> Biochemistry 23: 4828-4837, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6093867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6093867</a>] [<a href="https://doi.org/10.1021/bi00316a003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6093867">Long et al. (1984)</a> cloned a full-length human AAT cDNA from a liver cDNA library. Sequence analysis revealed a precursor molecule containing a 24-amino acid signal peptide and a mature protein of 394 amino acids. AAT is primarily synthesized in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6093867" 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="#35" class="mim-tip-reference" title="Crystal, R. G. <strong>Alpha-1-antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy.</strong> J. Clin. Invest. 85: 1343-1352, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2185272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2185272</a>] [<a href="https://doi.org/10.1172/JCI114578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2185272">Crystal (1990)</a> noted that hepatocytes are the major source of AAT, but that the gene is also expressed in mononuclear phagocytes and neutrophils. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2185272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#93" class="mim-tip-reference" title="Lai, E. C., Kao, F.-T., Law, M. L., Woo, S. L. C. <strong>Assignment of the alpha-1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization.</strong> Am. J. Hum. Genet. 35: 385-392, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6602546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6602546</a>]" pmid="6602546">Lai et al. (1983)</a> showed that the AAT gene contains 3 introns in the peptide-coding region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6602546" 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="#98" class="mim-tip-reference" title="Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W., Kurachi, K. <strong>Complete sequence of the cDNA for human alpha-1-antitrypsin and the gene for the S variant.</strong> Biochemistry 23: 4828-4837, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6093867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6093867</a>] [<a href="https://doi.org/10.1021/bi00316a003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6093867">Long et al. (1984)</a> found that the genomic length of the PI gene is 10.2 kb with a 1,434-bp coding region. The gene has 4 introns; exon 1, the 5-prime portion of exon 2, and the 3-prime portion of exon 5 are noncoding regions. The first intron, 5.3 kb long, contains a 143-amino acid open reading frame (which does not appear to be an actual protein coding region), an Alu family sequence, and a pseudotranscription initiation region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6093867" 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="#115" class="mim-tip-reference" title="Perlino, E., Cortese, R., Ciliberto, G. <strong>The human alpha-1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes.</strong> EMBO J. 6: 2767-2771, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3500042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3500042</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1987.tb02571.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3500042">Perlino et al. (1987)</a> found that the AAT gene in macrophages is transcribed from a macrophage-specific promoter located about 2,000 bp upstream of the hepatocyte-specific promoter. Transcription from the 2 AAT promoters is mutually exclusive; the macrophage promoter is silent in hepatocytes and the hepatocyte promoter is silent in macrophages. In macrophages, 2 distinct mRNAs are generated by alternative splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3500042" 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="#69" class="mim-tip-reference" title="Hafeez, W., Ciliberto, G., Perlmutter, D. H. <strong>Constitutive and modulated expression of the human alpha-1 antitrypsin gene: different transcriptional initiation sites used in three different cell types.</strong> J. Clin. Invest. 89: 1214-1222, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1556183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1556183</a>] [<a href="https://doi.org/10.1172/JCI115705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1556183">Hafeez et al. (1992)</a> demonstrated that the AAT gene has 3 macrophage-specific transcriptional initiation sites upstream from a single hepatocyte-specific transcriptional initiation site. Macrophages use these sites during basal and modulated expression. Hepatoma cells use the hepatocyte-specific transcriptional initiation site during basal and modulated expression but also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by the acute phase mediator interleukin-6 (IL6; <a href="/entry/147620">147620</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1556183" 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="#128" class="mim-tip-reference" title="Soutoglou, E., Talianidis, I. <strong>Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation.</strong> Science 295: 1901-1904, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11884757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11884757</a>] [<a href="https://doi.org/10.1126/science.1068356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11884757">Soutoglou and Talianidis (2002)</a> analyzed the ordered recruitment of factors to the human alpha-1-antitrypsin promoter around the initial activation of the gene during enterocyte differentiation. They found that a complete preinitiation complex, including phosphorylated RNA Pol II (<a href="/entry/180660">180660</a>), was assembled at the promoter long before transcriptional activation. The histone acetyltransferases CBP (<a href="/entry/600140">600140</a>) and P/CAF (<a href="/entry/602303">602303</a>) were recruited subsequently, but local histone hyperacetylation was delayed. After transient recruitment of the human Brahma homolog BRM (<a href="/entry/600014">600014</a>), remodeling of the neighboring nucleosome coincided with transcription initiation. <a href="#128" class="mim-tip-reference" title="Soutoglou, E., Talianidis, I. <strong>Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation.</strong> Science 295: 1901-1904, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11884757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11884757</a>] [<a href="https://doi.org/10.1126/science.1068356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11884757">Soutoglou and Talianidis (2002)</a> concluded that, at this promoter, chromatin reconfiguration is a defining step of the initiation process, acting after the assembly of the Pol II machinery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11884757" 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="#93" class="mim-tip-reference" title="Lai, E. C., Kao, F.-T., Law, M. L., Woo, S. L. C. <strong>Assignment of the alpha-1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization.</strong> Am. J. Hum. Genet. 35: 385-392, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6602546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6602546</a>]" pmid="6602546">Lai et al. (1983)</a> used a cloned AAT gene as a hybridization probe to analyze EcoRI-digested genomic DNA from different individuals and identified 2 distinct bands (9.6 kb and 8.5 kb long) in every case. Analysis using only intronic DNA as probe showed that the authentic gene resides in the 9.6-kb fragment. The 8.5-kb fragment was thought to contain a gene with close sequence homology to that of AAT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6602546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By studying hybrids of mouse or rat hepatoma cells with human lymphocytes, <a href="#40" class="mim-tip-reference" title="Darlington, G. J., Astrin, K. H., Muirhead, S. P., Desnick, R. J., Smith, M. <strong>Assignment of human alpha-1-antitrypsin to chromosome 14 by somatic cell hybrid analysis.</strong> Proc. Nat. Acad. Sci. 79: 870-873, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6801664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6801664</a>] [<a href="https://doi.org/10.1073/pnas.79.3.870" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6801664">Darlington et al. (1982)</a> and <a href="#114" class="mim-tip-reference" title="Pearson, S., Tetri, P., George, D. L., Francke, U. <strong>Alpha-1-antitrypsin (PI) expression in rat hepatoma-human somatic cell hybrids: evidence for PI locus on chromosome 14 and for regulatory locus on the X chromosome. (Abstract)</strong> Am. J. Hum. Genet. 33: 148A, 1981."None>Pearson et al. (1981)</a> achieved direct assignment of the PI locus to chromosome 14. From study of 2 families with abnormalities of the long arm of chromosome 14, <a href="#25" class="mim-tip-reference" title="Cox, D. W., Markovic, V. D., Teshima, I. E. <strong>Genes for immunoglobulin heavy chains and for alpha-1-antitrypsin are localized to specific regions of chromosome 14q.</strong> Nature 297: 428-430, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6804874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6804874</a>] [<a href="https://doi.org/10.1038/297428a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6804874">Cox et al. (1982)</a> localized GM to 14q32.3 and PI to a more proximal position between 14q24.3 and 14q32.1. The immunoglobulin genes are in a chromosome region noted for its high frequency of breaks associated with chromosome rearrangement, occurring both spontaneously in cultured lymphocytes and in certain malignancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6801664+6804874" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in situ hybridization, <a href="#121" class="mim-tip-reference" title="Schroeder, W. T., Miller, M. F., Woo, S. L. C., Saunders, G. F. <strong>Chromosomal localization of the human alpha-antitrypsin gene (PI) to 14q31-32.</strong> Am. J. Hum. Genet. 37: 868-872, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3876766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3876766</a>]" pmid="3876766">Schroeder et al. (1985)</a> narrowed the assignment of the PI locus to 14q31-q32. <a href="#131" class="mim-tip-reference" title="Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M., Arthuis, M., Jeanson, C. <strong>Two patients with interstitial del(14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin).</strong> Ann. Genet. 27: 237-240, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6335371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6335371</a>]" pmid="6335371">Turleau et al. (1984)</a> studied a patient with an interstitial deletion of 14q and assigned the PI locus to 14q32.1 by exclusion mapping. In a similar patient with an interstitial deletion of 14q, <a href="#139" class="mim-tip-reference" title="Yamamoto, Y., Sawa, R., Okamoto, N., Matsui, A., Yanagisawa, M., Ikemoto, S. <strong>Deletion 14q(q24.3 to q32.1) syndrome: significance of peculiar facial appearance in its diagnosis, and deletion mapping of Pi (alpha-1-antitrypsin).</strong> Hum. Genet. 74: 190-192, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3490426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3490426</a>] [<a href="https://doi.org/10.1007/BF00282092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3490426">Yamamoto et al. (1986)</a> confirmed the assignment to 14q32.1. By the dosage principle, the level of alpha-1-antitrypsin in the patient was only about half of that in his parents and in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3876766+3490426+6335371" 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="#123" class="mim-tip-reference" title="Sefton, L., Kearney, P., Kelsey, G., Povey, S., Wolfe, J. <strong>Physical linkage of the genes PI and AACT. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1076, 1989."None>Sefton et al. (1989)</a> used pulsed field gel electrophoresis to demonstrate that the genes encoding alpha-1-antitrypsin and alpha-1-antichymotrypsin (AACT, SERPINA3; <a href="/entry/107280">107280</a>) are approximately 220 kb apart and oriented in opposite directions.</p><p>Molecular studies of a ring chromosome 14 showed that the IGH and D14S1 loci were missing, whereas the PI locus was present (<a href="#86" class="mim-tip-reference" title="Keyeux, G., Gilgenkrantz, S., Lefranc, G., Lefranc, M.-P. <strong>Molecular characterization of a ring chromosome 14 showing that the PI locus is centromeric to the D14S1 and IGH loci.</strong> Hum. Genet. 82: 219-222, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2543620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2543620</a>] [<a href="https://doi.org/10.1007/BF00291158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2543620">Keyeux et al., 1989</a>). Thus, PI is proximal to the other 2 loci, a conclusion that was supported by much earlier data. A noncoding alpha-1-antitrypsin-like gene (PIL; <a href="/entry/107410">107410</a>) is located 12 kb 3-prime of the AAT gene. <a href="#6" class="mim-tip-reference" title="Billingsley, G. D., Walter, M. A., Cox, D. W. <strong>Physical linkage of alpha-1-antitrypsin and alpha-1-antichymotrypsin by pulsed field gel electrophoresis. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A130, 1989."None>Billingsley et al. (1989)</a> found that this gene and the AAT and AACT genes are carried by a single 550-kb NarI fragment. Also see <a href="#7" class="mim-tip-reference" title="Billingsley, G. D., Walter, M. A., Hammond, G. L., Cox, D. W. <strong>Physical mapping of four serpin genes: alpha-1-antitrypsin, alpha-1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome 14q32.1.</strong> Am. J. Hum. Genet. 52: 343-353, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8381582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8381582</a>]" pmid="8381582">Billingsley et al. (1993)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8381582+2543620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in situ hybridization, <a href="#95" class="mim-tip-reference" title="Ledbetter, S. A., Ledbetter, D. H., Ledley, F. D., Woo, S. <strong>Localization of phenylalanine hydroxylase (PAH) and alpha-1 antitrypsin (AAT) loci in mouse genome by synteny and in situ hybridization. (Abstract)</strong> Am. J. Hum. Genet. 41: A173, 1987."None>Ledbetter et al. (1987)</a> localized the AAT locus to mouse chromosome 12.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#42" class="mim-tip-reference" title="Dycaico, M. J., Grant, S. G. N., Felts, K., Nichols, W. S., Geller, S. A., Hager, J. H., Pollard, A. J., Kohler, S. W., Short, H. P., Jirik, F. R., Hanahan, D., Sorge, J. A. <strong>Neonatal hepatitis induced by alpha-1-antitrypsin: a transgenic mouse model.</strong> Science 242: 1409-1415, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3264419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3264419</a>] [<a href="https://doi.org/10.1126/science.3264419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3264419">Dycaico et al. (1988)</a> established transgenic mouse lineages that carried the normal (M) (see <a href="#0001">107400.0001</a>) or mutant (Z) (<a href="#0011">107400.0011</a>) alleles of the human AAT gene. All expressed the human protein in liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, particularly in hepatocytes, and was found in serum in concentrations 10 times lower than the M-allele protein. Mice in one lineage carrying the Z allele displayed significant runting in the neonatal period and had developed abnormalities in the liver with accumulation of human Z protein in diastase-resistant cytoplasmic globules that stained with periodic acid-Schiff reaction (PAS). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3264419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The major physiologic substrate of alpha-1-antitrypsin is elastase, particularly in the lower respiratory tract (<a href="#33" class="mim-tip-reference" title="Cox, D. W. <strong>Alpha-1-antitrypsin. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. IV. (8th ed.)</strong> New York: McGraw-Hill 2001. Pp. 5559-5584."None>Cox, 2001</a>).</p><p>AAT is an acute-phase reactant in that serum levels are increased with inflammation, trauma, and pregnancy (<a href="#32" class="mim-tip-reference" title="Cox, D. W. <strong>Alpha-1-antitrypsin deficiency. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic Basis of Inherited Disease. (6th ed.)</strong> New York: McGraw-Hill (pub.) 1989."None>Cox, 1989</a>).</p><p><strong><em>Alpha-1-Antitrypsin Deficiency</em></strong></p><p>
|
|
Deficiency of alpha-1-antitrypsin (<a href="/entry/613490">613490</a>) is primarily associated with the risk of emphysema and liver disease; see MOLECULAR GENETICS.</p><p><strong><em>Role in Twinning</em></strong></p><p>
|
|
<a href="#97" class="mim-tip-reference" title="Lieberman, J., Borhani, N. O., Feinleib, M. <strong>Alpha-1-antitrypsin deficiency in twins and parents-of-twins.</strong> Clin. Genet. 15: 29-36, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/310370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">310370</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1979.tb02026.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="310370">Lieberman et al. (1979)</a> found an increased frequency of heterozygosity for antitrypsin deficiency in twins and parents of twins. They concluded that 'increased' fertility and twinning may be heterozygous advantages for antitrypsin deficiency. <a href="#22" class="mim-tip-reference" title="Clark, P., Martin, N. G. <strong>An excess of the Pi(s) allele in dizygotic twins and their mothers.</strong> Hum. Genet. 61: 171-174, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982218</a>] [<a href="https://doi.org/10.1007/BF00274213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6982218">Clark and Martin (1982)</a> found that the frequency of the S allele (<a href="#0013">107400.0013</a>) in mothers of dizygotic twins (0.088) was double that in controls (0.044). The frequency of S in the parents of monozygotic twins and in fathers of DZ twins was no higher than in controls. Normal frequencies were observed for the Z allele (<a href="#0011">107400.0011</a>). No fertility indices other than twinning itself were available. To study relationships between Pi types, fertility, and twinning, <a href="#9" class="mim-tip-reference" title="Boomsma, D. I., Frants, R. R., Bank, R. A., Martin, N. G. <strong>Protease inhibitor (Pi) locus, fertility and twinning.</strong> Hum. Genet. 89: 329-332, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601424</a>] [<a href="https://doi.org/10.1007/BF00220552" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1601424">Boomsma et al. (1992)</a> studied 90 DZ and 70 MZ Dutch twin pairs and their parents. They found that mothers of dizygotic twins had frequencies of the S and Z alleles that were 3 times higher than those in a control sample. Mothers of identical twins also had a higher frequency of S than controls. The S allele may thus both increase ovulation rate and enhance the success of multiple pregnancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6982218+310370+1601424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Role in Human Immunodeficiency Virus-1 Infection</em></strong></p><p>
|
|
<a href="#15" class="mim-tip-reference" title="Bristow, C. L. <strong>Slow human immunodeficiency virus (HIV) infectivity correlated with low HIV coreceptor levels.</strong> Clin. Diagn. Lab. Immun. 8: 932-936, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11527806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11527806</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11527806[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/CDLI.8.5.932-936.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11527806">Bristow (2001)</a> found that decreased human immunodeficiency virus (HIV) infectivity correlated significantly with decreased cell surface expression of leukocyte (neutrophil) elastase (HLE) on monocytes but not lymphocytes. Decreased levels of PI correlated with increased cell surface HLE expression and increased HIV infectivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11527806" 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="#14" class="mim-tip-reference" title="Bristow, C. L., Patel, H., Arnold, R. R. <strong>Self antigen prognostic for human immunodeficiency virus disease progression.</strong> Clin. Diagn. Lab. Immun. 8: 937-942, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11527807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11527807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11527807[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/CDLI.8.5.937-942.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11527807">Bristow et al. (2001)</a> showed that decreased HIV viral load correlated with decreased circulating PI. Furthermore, asymptomatic patients manifested deficient levels of active PI. <a href="#14" class="mim-tip-reference" title="Bristow, C. L., Patel, H., Arnold, R. R. <strong>Self antigen prognostic for human immunodeficiency virus disease progression.</strong> Clin. Diagn. Lab. Immun. 8: 937-942, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11527807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11527807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11527807[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/CDLI.8.5.937-942.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11527807">Bristow et al. (2001)</a> noted that deficient levels of PI lead to degenerative lung diseases and suggested that preventing PI deficiency may prevent HIV-associated pathophysiology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11527807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using subclones of monocytic cell lines, <a href="#13" class="mim-tip-reference" title="Bristow, C. L., Mercatante, D. R., Kole, R. <strong>HIV-1 preferentially binds receptors copatched with cell-surface elastase.</strong> Blood 102: 4479-4486, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12933574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12933574</a>] [<a href="https://doi.org/10.1182/blood-2003-05-1635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12933574">Bristow et al. (2003)</a> showed that HLE localized to the cell surface, but not granules, of HIV-1-permissive clones, and to the granules, but not the cell surface, of HIV-1-nonpermissive clones. Stimulation of nonpermissive clones with lipopolysaccharide and LBP (<a href="/entry/151990">151990</a>), followed by exogenous PI, induced cell surface HLE expression, resulting in susceptibility to HIV infection. PI appeared to promote HIV coreceptor colocalization with surface HLE, thus permitting HIV infectivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12933574" 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="#126" class="mim-tip-reference" title="Shapiro, L., Pott, G. B., Ralston, A. H. <strong>Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1.</strong> FASEB J. 15: 115-122, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11149899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11149899</a>] [<a href="https://doi.org/10.1096/fj.00-0311com" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11149899">Shapiro et al. (2001)</a> showed that, at physiologic concentrations, AAT and CE-2072, a synthetic inhibitor of neutrophil elastase and proteinase-3 (PRTN3; <a href="/entry/177020">177020</a>), inhibited HIV-1 production in chronically infected monocytic cell lines, in fresh blood mononuclear cells infected after an activation step, and in permissive HeLa cells. EMSA analysis indicated that AAT suppressed activation of the HIV-1-inducing transcription factor NFKB (see <a href="/entry/164011">164011</a>). In 5 individuals with the Z-type AAT mutation (glu342lys; <a href="#0011">107400.0011</a>), HIV-1 p24 antigen increased more than 6-fold in whole blood after infection with a monocyte-tropic HIV strain. In contrast, there was no significant increase in blood obtained from healthy volunteers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11149899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By screening a peptide library generated from hemofiltrate, <a href="#104" class="mim-tip-reference" title="Munch, J., Standker, L., Adermann, K., Schulz, A., Schindler, M., Chinnadurai, R., Pohlmann, S., Chaipan, C., Biet, T., Peters, T., Meyer, B., Wilhelm, D., Lu, H., Jing, W., Jiang, S., Forssmann, W.-G., Kirchhoff, F. <strong>Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide.</strong> Cell 129: 263-275, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17448989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17448989</a>] [<a href="https://doi.org/10.1016/j.cell.2007.02.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17448989">Munch et al. (2007)</a> identified a 20-amino acid peptide from the C-proximal region of alpha-1-antitrypsin, designated virus-inhibitory peptide (VIRIP), as the most potent inhibitor of multiple HIV-1 strains, including those resistant to antiviral drugs. Changes in some VIRIP residues increased its antiviral potency 100-fold. VIRIP blocked HIV-1 entry by interacting with the virus gp41 fusion peptide. <a href="#104" class="mim-tip-reference" title="Munch, J., Standker, L., Adermann, K., Schulz, A., Schindler, M., Chinnadurai, R., Pohlmann, S., Chaipan, C., Biet, T., Peters, T., Meyer, B., Wilhelm, D., Lu, H., Jing, W., Jiang, S., Forssmann, W.-G., Kirchhoff, F. <strong>Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide.</strong> Cell 129: 263-275, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17448989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17448989</a>] [<a href="https://doi.org/10.1016/j.cell.2007.02.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17448989">Munch et al. (2007)</a> proposed that VIRIP may affect disease progression in HIV-1-infected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17448989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>NET Inhibitory Peptides</em></strong></p><p>
|
|
Neonatal neutrophils fail to form neutrophil extracellular traps (NETs) due to circulating NET inhibitory peptides (NIPs), which are cleavage fragments of A1AT. Using immunofluorescence assays, <a href="#16" class="mim-tip-reference" title="Campbell, R. A., Campbell, H. D., Bircher, J. S., de Araujo, C. V., Denorme, F., Crandell, J. L., Rustad, J. L., Monts, J., Cody, M. J., Kosaka, Y., Yost, C. C. <strong>Placental HTRA1 cleaves alpha-1-antitrypsin to generate a NET-inhibitory peptide.</strong> Blood 138: 977-988, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34192300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34192300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34192300[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2020009021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34192300">Campbell et al. (2021)</a> showed that human placenta from both term and preterm pregnancies secreted serine protease A1 (HTRA1; <a href="/entry/602194">602194</a>) into fetal circulation. Plasma HTRA1 levels were reduced after delivery, and decreased HTRA1 plasma levels were associated with decreased levels of NIPs. Placental HTRA1 cleaved A1AT after amino acid 382 to generate a C-terminal cleavage fragment of A1AT, termed A1ATM383S-CF, that could inhibit NET formation in vitro. Through NET inhibition, A1ATM383S-CF decreased bacterial killing, but it maintained other key neutrophil activities in vitro. In vivo analysis with wildtype mice showed that mouse placenta also secreted Htra1, and placental Htra1 cleaved A1at to generate A1atM383S-CF and inhibit NET formation by neonatal neutrophils. Analysis with Htra1 -/- and wildtype mice revealed that inhibition of NET formation during experimental neonatal sepsis improved survival. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34192300" 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="nomenclature" class="mim-anchor"></a>
|
|
<h4 href="#mimNomenclatureFold" id="mimNomenclatureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimNomenclatureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimNomenclatureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#55" class="mim-tip-reference" title="Fagerhol, M. K. <strong>The Pi system: genetic variants of serum alpha-1-antitrypsin.</strong> Ser. Haemat. 1: 153-161, 1968."None>Fagerhol (1968)</a> suggested that the system of inherited AAT variants be called Pi for protease inhibitor. <a href="#29" class="mim-tip-reference" title="Cox, D. W. <strong>Genetic variation in alpha-1-antitrypsin. (Editorial)</strong> Am. J. Hum. Genet. 30: 660-662, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/311585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">311585</a>]" pmid="311585">Cox (1978)</a> reported the recommendations of a workshop on PI nomenclature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=311585" 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>Many electrophoretic variants of serum alpha-1-antitrypsin have been described, beginning with those reported by <a href="#2" class="mim-tip-reference" title="Axelsson, U., Laurell, C. B. <strong>Hereditary variants of serum alpha-1-antitrypsin.</strong> Am. J. Hum. Genet. 17: 466-472, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4158556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4158556</a>]" pmid="4158556">Axelsson and Laurell (1965)</a>. <a href="#89" class="mim-tip-reference" title="Kueppers, F., Bearn, A. G. <strong>An inherited alpha-1-antitrypsin variant.</strong> Humangenetik 4: 217-220, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6080804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6080804</a>] [<a href="https://doi.org/10.1007/BF00292195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6080804">Kueppers and Bearn (1967)</a> studied an Italian family with multiple members heterozygous for an electrophoretic variant that could not be distinguished from that which <a href="#2" class="mim-tip-reference" title="Axelsson, U., Laurell, C. B. <strong>Hereditary variants of serum alpha-1-antitrypsin.</strong> Am. J. Hum. Genet. 17: 466-472, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4158556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4158556</a>]" pmid="4158556">Axelsson and Laurell (1965)</a> found in a Swedish family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4158556+6080804" 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>About 30 variants of alpha-1-antitrypsin had been described by 1981 (<a href="#77" class="mim-tip-reference" title="Hug, G., Chuck, G., Fagerhol, M. K. <strong>Pi(P-Clifton): a new alpha(1) antitrypsin allele in an American Negro family.</strong> J. Med. Genet. 18: 43-45, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6973024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6973024</a>] [<a href="https://doi.org/10.1136/jmg.18.1.43" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6973024">Hug et al., 1981</a>). The alleles were given symbols according to the relative electrophoretic mobility of the allele product. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6973024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Cox, D. W., Billingsley, G. D., Mansfield, T. <strong>DNA restriction-site polymorphisms associated with the alpha-1-antitrypsin gene.</strong> Am. J. Hum. Genet. 41: 891-906, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2890296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2890296</a>]" pmid="2890296">Cox et al. (1987)</a> studied RFLPs associated with the AAT gene. They gave information on extensive variability expressed by the polymorphic information content (PIC) as proposed by <a href="#10" class="mim-tip-reference" title="Botstein, D., White, R. L., Skolnick, M., Davis, R. W. <strong>Construction of a genetic linkage map in man using restriction fragment length polymorphisms.</strong> Am. J. Hum. Genet. 32: 314-331, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6247908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6247908</a>]" pmid="6247908">Botstein et al. (1980)</a>. PI types and M subtypes tended to be associated with specific RFLP haplotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2890296+6247908" 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="#107" class="mim-tip-reference" title="Nukiwa, T., Brantly, M. L., Ogushi, F., Fells, G. A., Crystal, R. G. <strong>Characterization of the gene and protein of the common alpha-1-antitrypsin normal M2 allele.</strong> Am. J. Hum. Genet. 43: 322-330, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901226</a>]" pmid="2901226">Nukiwa et al. (1988)</a> indicated that approximately 75 AAT alleles had been identified at the protein and/or gene level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2901226" 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="#118" class="mim-tip-reference" title="Roychoudhury, A. K., Nei, M. <strong>Human Polymorphic Genes: World Distribution.</strong> New York: Oxford Univ. Press (pub.) 1988. Pp. 132-135."None>Roychoudhury and Nei (1988)</a> tabulated worldwide gene frequencies for allelic variants M (M1, M2, M3, M4), S, Z, F, I, and V. <a href="#32" class="mim-tip-reference" title="Cox, D. W. <strong>Alpha-1-antitrypsin deficiency. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic Basis of Inherited Disease. (6th ed.)</strong> New York: McGraw-Hill (pub.) 1989."None>Cox (1989)</a> and <a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal (1989)</a> reviewed the variants, 'normal' and pathologic, of the PI gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>'Normal' Alleles</em></strong></p><p>
|
|
<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal (1989)</a> listed 10 normal AAT alleles that had been sequenced (<a href="#0001">107400.0001</a>-<a href="#0010">107400.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2696185" 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="#107" class="mim-tip-reference" title="Nukiwa, T., Brantly, M. L., Ogushi, F., Fells, G. A., Crystal, R. G. <strong>Characterization of the gene and protein of the common alpha-1-antitrypsin normal M2 allele.</strong> Am. J. Hum. Genet. 43: 322-330, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901226</a>]" pmid="2901226">Nukiwa et al. (1988)</a> stated that the most common alleles are the 2 forms of M1, that with valine at position 213 (M1V; <a href="#0002">107400.0002</a>) and that with alanine at position 213 (M1A; <a href="#0001">107400.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2901226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>'Risk' Alleles</em></strong></p><p>
|
|
<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal (1989)</a> divided AAT 'at risk' alleles into 'deficiency' alleles and 'null' alleles. He stated that except for the rare Pittsburgh allele (<a href="#0026">107400.0026</a>), which is associated with a bleeding disorder, only those phenotypes comprising 2 'at risk' alleles place the individual at risk for development of disease. Alleles in the 'at risk' class are found almost exclusively among Caucasians of European descent, with the highest frequency in northern Europe. Blacks and Asians are rarely affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The most common AAT deficiency allele is the Z allele (glu342-to lys; <a href="#0011">107400.0011</a>), which occurs on an M1A (ala213; <a href="#0001">107400.0001</a>) haplotype background (<a href="#106" class="mim-tip-reference" title="Nukiwa, T., Brantly, M., Garver, R., Paul, L., Courtney, M., LeCocq, J.-P., Crystal, R. G. <strong>Evaluation of 'at risk' alpha-1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes.</strong> J. Clin. Invest. 77: 528-537, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484754</a>] [<a href="https://doi.org/10.1172/JCI112333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3484754">Nukiwa et al., 1986</a>). The homozygous ZZ phenotype is associated with a high risk of both emphysema and liver disease. The Z allele reaches polymorphic frequencies in Caucasians and is rare or absent in Asians and blacks (<a href="#41" class="mim-tip-reference" title="DeCroo, S., Kamboh, M. I., Ferrell, R. E. <strong>Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.</strong> Hum. Hered. 41: 215-221, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783408</a>] [<a href="https://doi.org/10.1159/000154004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1783408">DeCroo et al., 1991</a>; <a href="#79" class="mim-tip-reference" title="Hutchison, D. C. S. <strong>Alpha-1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z.</strong> Respir. Med. 92: 367-377, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9692092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9692092</a>] [<a href="https://doi.org/10.1016/s0954-6111(98)90278-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9692092">Hutchison, 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1783408+3484754+9692092" 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="Clark, P., Breit, S. N., Dawkins, R. L., Penny, R. <strong>Genetic study of a family with two members with Weber-Christian disease (panniculitis) and alpha-1-antitrypsin deficiency.</strong> Am. J. Med. Genet. 13: 57-62, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982619</a>] [<a href="https://doi.org/10.1002/ajmg.1320130110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6982619">Clark et al. (1982)</a> reported the cases of 2 brothers with Weber-Christian panniculitis and the AAT Z phenotype. A younger brother had the Z phenotype without Weber-Christian disease. Along with several earlier reported cases, these observations establish a relationship. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982619" 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>Another common AAT deficiency allele is the S allele (glu264-to-val; <a href="#0013">107400.0013</a>), which occurs on an M1V (val213; <a href="#0002">107400.0002</a>) haplotype background. Pi*S homozygotes are at no risk of emphysema, but compound heterozygotes with a Z or a null allele have a mildly increased risk (<a href="#37" class="mim-tip-reference" title="Curiel, D. T., Chytil, A., Courtney, M., Crystal, R. G. <strong>Serum alpha-1-antitrypsin deficiency associated with the common S-type (glu264-to-val) mutation results from intracellular degradation of alpha-1-antitrypsin prior to secretion.</strong> J. Biol. Chem. 264: 10477-10486, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2567291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2567291</a>]" pmid="2567291">Curiel et al., 1989</a>). The S allele reaches polymorphic frequencies in Caucasians and is rare or absent in Asians and blacks. It is not associated with liver disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2567291" 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>Other rare deficiency AAT alleles may result in increased risk for both liver and lung disease (e.g., Pi M(Malton); <a href="#0012">107400.0012</a>) or only emphysema (e.g., Pi M(Procida); <a href="#0016">107400.0016</a>). Some of the rare deficiency alleles have been found in Japanese (e.g., Pi S(Iiyama); <a href="#0039">107400.0039</a>).</p><p>Null AAT alleles are rare but have been found in all populations. <a href="#60" class="mim-tip-reference" title="Garver, R. I., Jr., Mornex, J.-F., Nukiwa, T., Brantly, M., Courtney, M., LeCocq, J.-P., Crystal, R. G. <strong>Alpha-1-antitrypsin deficiency and emphysema caused by homozygous inheritance of non-expressing alpha-1-antitrypsin genes.</strong> New Eng. J. Med. 314: 762-766, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485249</a>] [<a href="https://doi.org/10.1056/NEJM198603203141207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3485249">Garver et al. (1986)</a> investigated the molecular basis of the Pi null-null AAT phenotype. The gene appeared to be intact without discernible deletion or other structural abnormality, yet there was no detectable mRNA produced. The 5-prime promoter region also appeared to be normal. No evidence of hypermethylation of cytosine nucleotides in the promoter region was detected. The defect may be comparable to that in some forms of thalassemia in which a change, at a splicing site, for example, may lead to greatly reduced mRNA production. The null-null phenotype is accompanied by emphysema as is the ZZ and SZ phenotypes but an important difference is that cirrhosis and liver disease do not occur with the null-null phenotype; there is no abnormal antitrypsin produced that is excreted with difficulty from the cells of synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485249" 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="#109" class="mim-tip-reference" title="Nukiwa, T., Takahashi, H., Brantly, M., Courtney, M., Crystal, R. G. <strong>Alpha-1-antitrypsin null (Granite Falls), a nonexpressing alpha-1-antitrypsin gene associated with a frameshift to stop mutation in a coding exon.</strong> J. Biol. Chem. 262: 11999-12004, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3040726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3040726</a>]" pmid="3040726">Nukiwa et al. (1987)</a> identified a null form of alpha-1-antitrypsin resulting from a frameshift causing a stop codon to be formed approximately 44% from the N terminus of the precursor protein (Null(Granite Falls); <a href="#0020">107400.0020</a>). Although the molecular basis of antitrypsin deficiency was quite different from that in the Z haplotype, the phenotypic consequences were similar: severe deficiency associated with high risk of emphysema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3040726" 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="#124" class="mim-tip-reference" title="Seixas, S., Mendonca, C., Costa, F., Rocha, J. <strong>Alpha-1-antitrypsin null alleles: evidence for the recurrence of the L353fsX376 mutation and a novel G-to-A transition in position +1 of intron IC affecting normal mRNA splicing.</strong> Clin. Genet. 62: 175-180, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220457</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620212.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12220457">Seixas et al. (2002)</a> reported 2 null alleles of the PI gene in Portuguese patients with emphysema. These alleles were associated with total lack of circulating protein as indicated by the absence of isoelectric focusing banding patterns. One of the alleles, designated Q0(Ourem), was identical to Q0(Mattawa) on an M3 normal background (<a href="#0022">107400.0022</a>). The second allele, Q0(Porto), had a novel mutation which restricted mononuclear phagocyte transcripts to mRNA species resulting from the direct splice of exon IA to exon II. The absence of this normal splice alternative in the liver, where PI is primarily synthesized, provided a basis for the pathogenic effects of this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>PI Pittsburgh</em></strong></p><p>
|
|
The PI Pittsburgh allele (met358-to-arg; <a href="#0026">107400.0026</a>), which occurs at the AAT active site, is an example of a mutation leading to altered function of the gene product. AAT becomes a potent inhibitor of thrombin and factor XI rather than of elastase. The mutation results in a bleeding disorder (<a href="#96" class="mim-tip-reference" title="Lewis, J. H., Iammarino, R. M., Spero, J. A., Hasiba, U. <strong>Antithrombin Pittsburgh: an alpha-1-antitrypsin variant causing hemorrhagic disease.</strong> Blood 51: 129-137, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/412531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">412531</a>]" pmid="412531">Lewis et al., 1978</a>; <a href="#111" class="mim-tip-reference" title="Owen, M. C., Brennan, S. O., Lewis, J. H., Carrell, R. W. <strong>Mutation of antitrypsin to antithrombin: alpha-1-antitrypsin Pittsburgh (358 met-to-arg), a fatal bleeding disorder.</strong> New Eng. J. Med. 309: 694-698, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6604220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6604220</a>] [<a href="https://doi.org/10.1056/NEJM198309223091203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6604220">Owen et al., 1983</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=412531+6604220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>SERPINA1 Haplotypes Associated with Chronic Obstructive Pulmonary Disease</em></strong></p><p>
|
|
While cigarette smoking is a major cause of COPD (see <a href="/entry/606963">606963</a>), only 15% of smokers develop the disease, indicating major genetic influences. The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 (<a href="/entry/107280">107280</a>) may also play a role. <a href="#19" class="mim-tip-reference" title="Chappell, S., Daly, L., Morgan, K., Baranes, T. G., Roca, J., Rabinovich, R., Millar, A., Donnelly, S. C., Keatings, V., MacNee, W., Stolk, J., Hiemstra, P., Miniati, M., Monti, S., O'Connor, C. M., Kalsheker, N. <strong>Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease.</strong> Hum. Mutat. 27: 103-109, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278826</a>] [<a href="https://doi.org/10.1002/humu.20275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278826">Chappell et al. (2006)</a> identified 15 single-nucleotide polymorphism (SNP) haplotype tags from high-density SNP maps of the 2 genes and evaluated these SNPs in the largest case-control genetic study of COPD conducted to that time. For SERPINA1, 6 newly identified haplotypes with a common backbone of 5 SNPs were found to increase the risk of disease by 6- to 50-fold, the highest risk of COPD that had been reported. In contrast, no haplotype associations for SERPINA3 were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#41" class="mim-tip-reference" title="DeCroo, S., Kamboh, M. I., Ferrell, R. E. <strong>Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.</strong> Hum. Hered. 41: 215-221, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783408</a>] [<a href="https://doi.org/10.1159/000154004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1783408">DeCroo et al. (1991)</a> studied the frequency of alpha-1-antitrypsin alleles in US whites, US blacks, and African blacks (living in Nigeria). While the PI*S allele was present at a polymorphic level in US whites, it was present only sporadically in US blacks and completely absent in African blacks. The PI*Z allele was not detected in the black populations tested. <a href="#41" class="mim-tip-reference" title="DeCroo, S., Kamboh, M. I., Ferrell, R. E. <strong>Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.</strong> Hum. Hered. 41: 215-221, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783408</a>] [<a href="https://doi.org/10.1159/000154004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1783408">DeCroo et al. (1991)</a> used the PI allele frequency data to calculate white admixture in US blacks. The average white admixture estimate in US blacks, based on all PI alleles, was about 13%. This value was about 24% when only the S and Z alleles were used. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1783408" 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>Studies of the distribution of the S and Z alleles in Europe demonstrated that they occur mainly among those of European stock. <a href="#79" class="mim-tip-reference" title="Hutchison, D. C. S. <strong>Alpha-1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z.</strong> Respir. Med. 92: 367-377, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9692092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9692092</a>] [<a href="https://doi.org/10.1016/s0954-6111(98)90278-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9692092">Hutchison (1998)</a> found that the frequency of the gene for PiZ is highest on the northwestern seaboard of the continent and that the mutation seems to have arisen in southern Scandinavia. The distribution of PiS is quite different: the gene frequency is highest in the Iberian peninsula and the mutation is likely to have arisen in that region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9692092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By means of a metaanalysis of 43 studies, <a href="#8" class="mim-tip-reference" title="Blanco, I., Bustillo, E. F., Rodriguez, M. C. <strong>Distribution of alpha-1-antitrypsin PI S and PI Z frequencies in countries outside Europe: a meta-analysis.</strong> Clin. Genet. 60: 431-441, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11846735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11846735</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.600605.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11846735">Blanco et al. (2001)</a> analyzed the distribution of the PI*S and PI*Z alleles in countries outside Europe and compared them with data from Europe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11846735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The pallid (pa) (<a href="/entry/604310">604310</a>) mouse develops emphysema late in life. <a href="#101" class="mim-tip-reference" title="Martorana, P. A., Brand, T., Gardi, C., van Even, P., de Santi, M. M., Calzoni, P., Marcolongo, P., Lungarella, G. <strong>The pallid mouse: a model of genetic alpha-1-antitrypsin deficiency.</strong> Lab. Invest. 68: 233-241, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8441253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8441253</a>]" pmid="8441253">Martorana et al. (1993)</a> demonstrated that pallid mice have markedly reduced levels of serum alpha-1-antitrypsin associated with severe deficiency in serum elastase inhibitory capacity. However, they have normal alpha-1-antitrypsin mRNA levels in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8441253" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#68" class="mim-tip-reference" title="Green, C., Brown, G., Dafforn, T. R., Reichhart, J.-M., Morley, T., Lomas, D. A., Gubb, D. <strong>Drosophila necrotic mutations mirror disease-associated variants of human serpins.</strong> Development 130: 1473-1478, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588861</a>] [<a href="https://doi.org/10.1242/dev.00350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12588861">Green et al. (2003)</a> showed that Drosophila 'necrotic' (nec) mutations can mimic alpha-1-antitrypsin deficiency. They identified 2 nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an amino acid substitution equivalent to that found in S(Iiyama) variant antitrypsin (<a href="#0039">107400.0039</a>) failed to complement nec-null mutations and demonstrated a dominant temperature-dependent inactivation of the wildtype nec allele. <a href="#68" class="mim-tip-reference" title="Green, C., Brown, G., Dafforn, T. R., Reichhart, J.-M., Morley, T., Lomas, D. A., Gubb, D. <strong>Drosophila necrotic mutations mirror disease-associated variants of human serpins.</strong> Development 130: 1473-1478, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588861</a>] [<a href="https://doi.org/10.1242/dev.00350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12588861">Green et al. (2003)</a> concluded that the Drosophila nec system can be used as a powerful system to study serpin polymerization in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588861" 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="#132" class="mim-tip-reference" title="van Pel, M., van Os, R., Velders, G. A., Hagoort, H., Heegaard, P. M. H., Lindley, I. J. D., Willemze, R., Fibbe, W. E. <strong>Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization.</strong> Proc. Nat. Acad. Sci. 103: 1469-1474, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16432201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16432201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16432201[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0510192103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16432201">Van Pel et al. (2006)</a> reported that IL8 (<a href="/entry/146930">146930</a>)- and GCSF (CSF3; <a href="/entry/138970">138970</a>)-induced mobilization of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in mice was completely inhibited by total body irradiation (TBI). They found that TBI increased expression of Serpina1 mRNA and protein, which inhibited elastase activity. Inhibition of HSC/HPC mobilization in irradiated mice could be reversed by anti-Serpina1. Furthermore, injection of Serpina1, but not heat-inactivated Serpina1, prior to administration of IL8 inhibited HSC/HPC mobilization. <a href="#132" class="mim-tip-reference" title="van Pel, M., van Os, R., Velders, G. A., Hagoort, H., Heegaard, P. M. H., Lindley, I. J. D., Willemze, R., Fibbe, W. E. <strong>Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization.</strong> Proc. Nat. Acad. Sci. 103: 1469-1474, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16432201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16432201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16432201[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0510192103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16432201">Van Pel et al. (2006)</a> concluded that low-dose TBI induces Serpina1 in bone marrow and inhibits HSC/HPC mobilization, and they hypothesized that cytokine-induced HSC/HPC mobilization is determined by a critical balance between serine proteases and their inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16432201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#83" class="mim-tip-reference" title="Kamimoto, T., Shoji, S., Hidvegi, T., Mizushima, N., Umebayashi, K., Perlmutter, D. H., Yoshimori, T. <strong>Intracellular inclusions containing mutant alpha(1)-antitrypsin Z are propagated in the absence of autophagic activity.</strong> J. Biol. Chem. 281: 4467-4476, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16365039/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16365039</a>] [<a href="https://doi.org/10.1074/jbc.M509409200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16365039">Kamimoto et al. (2006)</a> bred the PiZ mouse onto the GFP-LC3 background to monitor autophagy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16365039" 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="#70" class="mim-tip-reference" title="Hidvegi, T., Ewing, M., Hale, P., Dippold, C., Beckett, C., Kemp, C., Maurice, N., Mukherjee, A., Goldbach, C., Watkins, S., Michalopoulos, G., Perlmutter, D. H. <strong>An autophagy-enhancing drug promotes degradation of mutant alpha-1-antitrypsin Z and reduces hepatic fibrosis.</strong> Science 329: 229-232, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20522742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20522742</a>] [<a href="https://doi.org/10.1126/science.1190354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20522742">Hidvegi et al. (2010)</a> demonstrated that the autophagy-enhancing drug carbamazepine decreased the hepatic load of mutant alpha-1-antitrypsin Z (ATZ) protein and hepatic fibrosis in a mouse model of AAT deficiency-associated liver disease. The mouse used was the PiZ mouse, developed by <a href="#42" class="mim-tip-reference" title="Dycaico, M. J., Grant, S. G. N., Felts, K., Nichols, W. S., Geller, S. A., Hager, J. H., Pollard, A. J., Kohler, S. W., Short, H. P., Jirik, F. R., Hanahan, D., Sorge, J. A. <strong>Neonatal hepatitis induced by alpha-1-antitrypsin: a transgenic mouse model.</strong> Science 242: 1409-1415, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3264419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3264419</a>] [<a href="https://doi.org/10.1126/science.3264419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3264419">Dycaico et al. (1988)</a>, in which the human ATZ gene is a transgene. Although the PiZ mouse has normal circulating levels of endogenous murine alpha-1-antitrypsin, it is a robust model of liver disease associated with AAT deficiency, as characterized by intrahepatocytic ATZ-containing globules, inflammation, and increased regenerative activity, dysplasia, and fibrosis. <a href="#70" class="mim-tip-reference" title="Hidvegi, T., Ewing, M., Hale, P., Dippold, C., Beckett, C., Kemp, C., Maurice, N., Mukherjee, A., Goldbach, C., Watkins, S., Michalopoulos, G., Perlmutter, D. H. <strong>An autophagy-enhancing drug promotes degradation of mutant alpha-1-antitrypsin Z and reduces hepatic fibrosis.</strong> Science 329: 229-232, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20522742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20522742</a>] [<a href="https://doi.org/10.1126/science.1190354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20522742">Hidvegi et al. (2010)</a> concluded that their results in this animal model provided a basis for testing carbamazepine, which has an extensive clinical safety profile in patients with AAT deficiency (<a href="/entry/613490">613490</a>) and also provided proof of principle for therapeutic use of autophagy enhancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20522742+3264419" 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>The polymorphism of prealbumin described by <a href="#48" class="mim-tip-reference" title="Fagerhol, M. K., Braend, M. <strong>Serum prealbumin: polymorphism in man.</strong> Science 149: 986-987, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5827347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5827347</a>] [<a href="https://doi.org/10.1126/science.149.3687.986" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5827347">Fagerhol and Braend (1965)</a> was shown by <a href="#52" class="mim-tip-reference" title="Fagerhol, M. K., Laurell, C. B. <strong>The polymorphism of 'prealbumins' and alpha-1-antitrypsin in human sera.</strong> Clin. Chim. Acta 16: 199-203, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4166396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4166396</a>] [<a href="https://doi.org/10.1016/0009-8981(67)90181-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4166396">Fagerhol and Laurell (1967)</a> to be the same as the alpha-1-antitrypsin polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5827347+4166396" 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 possible heterogeneity in recombination frequency between Pi variants believed to be allelic was reported by <a href="#63" class="mim-tip-reference" title="Gedde-Dahl, T., Jr., Fagerhol, M. K., Cook, P. J. L., Noades, J. <strong>Autosomal linkage between the Gm and Pi loci in man.</strong> Ann. Hum. Genet. 35: 393-400, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5073686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5073686</a>]" pmid="5073686">Gedde-Dahl et al. (1972)</a>: Pi(Z) had less recombination with Gm than Pi(non-Z). <a href="#62" class="mim-tip-reference" title="Gedde-Dahl, T., Jr., Cook, P. J. L., Fagerhol, M. K., Pierce, J. A. <strong>The Gm-Pi linkage: a summary estimate.</strong> Birth Defects Orig. Art. Ser. XI(3): 157-158, 1975. Note: Alternate: Cytogenet. Cell Genet. 14: 327-328, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/54196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">54196</a>]" pmid="54196">Gedde-Dahl et al. (1975)</a> gave further data on the Gm-Pi linkage. They considered heterogeneity of recombination fraction among males of different Pi types to be likely. The major difference seemed to be between the Pi(Z) and other alleles. Possible explanations included a chromosomal deletion, inversion or locus regulating recombination in linkage disequilibrium with the Pi locus. <a href="#64" class="mim-tip-reference" title="Gedde-Dahl, T., Jr., Frants, R., Olaisen, B., Eriksson, A. W., van Loghem, E., Lamm, L. <strong>The Gm-Pi linkage heterogeneity in view of Pi M subtypes.</strong> Ann. Hum. Genet. 45: 143-153, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6797346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6797346</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1981.tb00316.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6797346">Gedde-Dahl et al. (1981)</a> showed that the allele-specific heterogeneity of Gm-Pi linkage is attributable to 'reduced' recombination in Z-allele heterozygotes. They found an equal sex ratio for Pi 'non-Z' variants, as opposed to a 1:2 male-female ratio for 'Z' families. The location of Gm and Pi on 6p was excluded by <a href="#5" class="mim-tip-reference" title="Bender, K., Muller, C. R., Schmidt, A., Strohmaier, U., Wienker, T. F. <strong>Linkage studies on the human Pi, Gm, GLO, and HLA genes.</strong> Hum. Genet. 49: 159-166, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/112033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">112033</a>] [<a href="https://doi.org/10.1007/BF00277637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="112033">Bender et al. (1979)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5073686+6797346+112033+54196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Babron, M. C., Constans, J., Dugoujon, J. M., Cambon-Thomsen, A., Bonaiti-Pellie, C. <strong>The Gm-Pi linkage in 843 French families: effect of the alleles Pi Z and Pi S.</strong> Ann. Hum. Genet. 54: 107-113, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2382967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2382967</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1990.tb00366.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2382967">Babron et al. (1990)</a> confirmed a previous finding that the presence of the Pi Z allele tends to decrease the recombination rate between the GM (<a href="/entry/147100">147100</a>) and PI loci. This decrease appeared to be similar in both sexes and not unique in males as previously noted. The results suggested a possible linkage disequilibrium between the Pi Z allele and a large inversion between the GM and PI loci. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2382967" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Carrell, R. W. <strong>Alpha-1-antitrypsin: molecular pathology, leukocytes, and tissue damage.</strong> J. Clin. Invest. 78: 1427-1431, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3537008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3537008</a>] [<a href="https://doi.org/10.1172/JCI112731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3537008">Carrell (1986)</a> cited evidence for the existence of 2 genes coding for alpha-1-antitrypsin, although the plasma findings were compatible with expression of the alleles at a single locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3537008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>40 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/107400" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=107400[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PI M1-ALA213</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI, M1A
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ALA213
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs6647 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6647;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs6647?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs6647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs6647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019553 OR RCV000019554 OR RCV000151834 OR RCV000406073 OR RCV001701482 OR RCV002362589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019553, RCV000019554, RCV000151834, RCV000406073, RCV001701482, RCV002362589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019553...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>M1A, a normal variant, is believed to be the 'oldest' human PI allele, with the other common normal alleles M1V (<a href="#0002">107400.0002</a>), M2 (<a href="#0003">107400.0003</a>), and M3 (<a href="#0004">107400.0004</a>) derived from M1A by single base substitutions. M2 is derived from M3; it has the same amino acid difference that distinguishes M3 from M1V but a second substitution in addition. The 4 common normal alleles are considered the 'base' from which all the other alleles are derived (see Fig. 4 in <a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). The M1A allele has a frequency of 0.20-0.23 in US Caucasians. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PI M1-VAL213</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI, M1V
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ALA213
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs6647 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6647;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs6647?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs6647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs6647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019555 OR RCV000019556 OR RCV002362590" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019555, RCV000019556, RCV002362590" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019555...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This normal allele has a frequency of 0.44-0.49 in US Caucasians.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PI M2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ARG101HIS ON M3
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs709932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs709932;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs709932?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs709932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs709932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019557 OR RCV000019559 OR RCV000155576 OR RCV000310904 OR RCV001636605 OR RCV002345248" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019557, RCV000019559, RCV000155576, RCV000310904, RCV001636605, RCV002345248" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019557...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>M2, which has a frequency of 0.10-0.11 in US Caucasians (<a href="#32" class="mim-tip-reference" title="Cox, D. W. <strong>Alpha-1-antitrypsin deficiency. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic Basis of Inherited Disease. (6th ed.)</strong> New York: McGraw-Hill (pub.) 1989."None>Cox, 1989</a>), was studied by <a href="#107" class="mim-tip-reference" title="Nukiwa, T., Brantly, M. L., Ogushi, F., Fells, G. A., Crystal, R. G. <strong>Characterization of the gene and protein of the common alpha-1-antitrypsin normal M2 allele.</strong> Am. J. Hum. Genet. 43: 322-330, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901226</a>]" pmid="2901226">Nukiwa et al. (1988)</a>, who found that its coding exons are identical to those of the more frequent form of M1 (val213) except for 2 bases: a change in codon 101 from CGT to CAT, leading to an amino acid change of arginine to histidine; and a change in codon 376 from GAA to GAC, resulting in an amino acid change from glutamic acid to aspartic acid. Since 2 mutations separate these 2 common alleles, <a href="#107" class="mim-tip-reference" title="Nukiwa, T., Brantly, M. L., Ogushi, F., Fells, G. A., Crystal, R. G. <strong>Characterization of the gene and protein of the common alpha-1-antitrypsin normal M2 allele.</strong> Am. J. Hum. Genet. 43: 322-330, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901226</a>]" pmid="2901226">Nukiwa et al. (1988)</a> suggested that another AAT variant (presumably M3) was an intermediate in their evolution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2901226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PI M3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLU376ASP ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1303 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1303;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1303?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019558 OR RCV000155574 OR RCV000380179 OR RCV001650837 OR RCV002345249" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019558, RCV000155574, RCV000380179, RCV001650837, RCV002345249" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019558...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This normal variant allele has a frequency of 0.14-0.19 among US Caucasians. <a href="#65" class="mim-tip-reference" title="Graham, A., Hayes, K., Weidinger, S., Newton, C. R., Markham, A. F., Kalsheker, N. A. <strong>Characterisation of the alpha-1-antitrypsin M3 gene, a normal variant.</strong> Hum. Genet. 85: 381-382, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2394452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2394452</a>] [<a href="https://doi.org/10.1007/BF00206766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2394452">Graham et al. (1990)</a> identified a single nucleotide difference between M1 (val213) and M3: a transversion in codon 376 from GAA(glu) to GAC(asp). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2394452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PI M4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ARG101HIS ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019557 OR RCV000019559 OR RCV000155576 OR RCV000310904 OR RCV001636605 OR RCV002345248" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019557, RCV000019559, RCV000155576, RCV000310904, RCV001636605, RCV002345248" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019557...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>M4, an uncommon normal allele, is likely derived by single substitution from M1V; however, it has the same mutation that changed M2 to M3, and thus it is possible that M4 derived from M3 (or vice versa).</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PI B(ALHAMBRA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ASP-LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019560</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#140" class="mim-tip-reference" title="Yoshida, A., Chillar, R., Taylor, J. C. <strong>An alpha-1-antitrypsin variant, PiB Alhambra (lys-to-asp, glu-to-asp), with rapid anodal electrophoretic mobility.</strong> Am. J. Hum. Genet. 31: 555-563, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/315708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">315708</a>]" pmid="315708">Yoshida et al. (1979)</a> found 2 amino acid substitutions in the rare antitrypsin variant PiB Alhambra. One substitution was asp for lys at an unknown location (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2696185+315708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PI F</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ARG223CYS ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28929470 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28929470;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28929470?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28929470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28929470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019561 OR RCV000148879 OR RCV000151833 OR RCV000205893 OR RCV000622899 OR RCV000727618 OR RCV004724750" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019561, RCV000148879, RCV000151833, RCV000205893, RCV000622899, RCV000727618, RCV004724750" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019561...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This rare 'normal' allele has a CGT-to-TGT change in codon 223 (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>; <a href="#110" class="mim-tip-reference" title="Okayama, H., Brantly, M., Holmes, M., Crystal, R. G. <strong>Characterization of the molecular basis of the alpha-1-antitrypsin F allele.</strong> Am. J. Hum. Genet. 48: 1154-1158, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2035534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2035534</a>]" pmid="2035534">Okayama et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2696185+2035534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 PI P(ST. ALBANS)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ASP341ASN ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs143370956 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs143370956;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs143370956?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs143370956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs143370956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28929471 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28929471;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28929471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28929471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019562 OR RCV000148874 OR RCV000178751 OR RCV004748529" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019562, RCV000148874, RCV000178751, RCV004748529" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019562...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In addition to a GAC-to-AAC change in codon 341, this rare 'normal' allele has a 'silent' asp256 (GAT)-to-asp256 (GAC) change. The rare P-family of AAT variants is defined by the position of migration of the protein on isoelectric focusing (IEF) of serum between the common M and S variants. The P(St. Albans) allele is associated with normal serum levels of AAT, whereas the P(Lowell) allele (<a href="#0019">107400.0019</a>) is associated with reduced levels. <a href="#74" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Crystal, R. G. <strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong> Am. Rev. Resp. Dis. 142: 1185-1192, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2240842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2240842</a>] [<a href="https://doi.org/10.1164/ajrccm/142.5.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2240842">Holmes et al. (1990)</a> described the DNA change underlying both of these variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2240842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 PI X</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLU204LYS ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs199422208 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422208;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs199422208?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199422208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199422208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019563 OR RCV000512615 OR RCV002260969" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019563, RCV000512615, RCV002260969" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019563...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This rare 'normal' allele has been sequenced only at the level of the protein (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 PI CHRISTCHURCH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLU363LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912712 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912712;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912712?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019564 OR RCV000201867 OR RCV000597262 OR RCV003964806" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019564, RCV000201867, RCV000597262, RCV003964806" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019564...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#12" class="mim-tip-reference" title="Brennan, S. O., Carrell, R. W. <strong>Alpha-1-antitrypsin Christchurch, 363 glu-to-lys: mutation at the P-prime-5 position does not affect inhibitory activity.</strong> Biochim. Biophys. Acta 873: 13-19, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3527273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3527273</a>] [<a href="https://doi.org/10.1016/0167-4838(86)90183-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3527273">Brennan and Carrell (1986)</a> characterized antitrypsin Christchurch, which shows a substitution of lysine for glutamic acid at position 363. Although electrophoretic mobility of the mutant protein was abnormal, no functional abnormality of the protein was detected. The base PI allele, M1A or M1V, is unknown (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3527273+2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 PI Z</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLU342LYS ON M1A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28929474 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28929474;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28929474?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28929474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28929474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019567 OR RCV000019594 OR RCV000019595 OR RCV000148877 OR RCV000194811 OR RCV000255454 OR RCV000623762 OR RCV000768543 OR RCV001195107 OR RCV002054450 OR RCV002251912 OR RCV002276567 OR RCV002466247 OR RCV003415721" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019567, RCV000019594, RCV000019595, RCV000148877, RCV000194811, RCV000255454, RCV000623762, RCV000768543, RCV001195107, RCV002054450, RCV002251912, RCV002276567, RCV002466247, RCV003415721" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019567...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This is the most frequent allele leading to a high risk of emphysema (and liver disease) in the homozygote; the allele frequency is 0.01-0.02 in US Caucasians (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). <a href="#106" class="mim-tip-reference" title="Nukiwa, T., Brantly, M., Garver, R., Paul, L., Courtney, M., LeCocq, J.-P., Crystal, R. G. <strong>Evaluation of 'at risk' alpha-1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes.</strong> J. Clin. Invest. 77: 528-537, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484754</a>] [<a href="https://doi.org/10.1172/JCI112333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3484754">Nukiwa et al. (1986)</a> demonstrated the val213-to-ala substitution (here symbolized M1A) in PI*Z in addition to the disease-producing glu342-to-lys mutation. Ala213 was found in all of 40 Z haplotypes, using synthetic oligonucleotide gene probes directed toward the mutated exon 3 sequences in the Z gene. Furthermore, the exon 3 mutation eliminated a BstEII restriction endonuclease site, allowing rapid identification of the change in genomic DNA. Surprisingly, only 23% of the M1 haplotypes were found to be BstEII site negative. The new form of M1, i.e., M1(ala213), is identical to M1 but has an isoelectric focusing 'silent' amino acid substitution. M1 has a frequency of 68 to 76%; M2, 14 to 20%; and M3, 10 to 12%. The Z gene represents 1 to 2% of all alpha-1-antitrypsin haplotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2696185+3484754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using 2 genomic probes extending into the 5-prime and 3-prime flanking regions, respectively, <a href="#27" class="mim-tip-reference" title="Cox, D. W., Woo, S. L. C., Mansfield, T. <strong>DNA restriction fragments associated with alpha-1-antitrypsin indicate a single origin for deficiency allele PI Z.</strong> Nature 316: 79-81, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2989709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2989709</a>] [<a href="https://doi.org/10.1038/316079a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2989709">Cox et al. (1985)</a> identified 8 polymorphic restriction sites for the PI gene. Extensive linkage disequilibrium was found with the PI Z allele throughout the probe region, but not with the normal PI M allele. The Z allele occurred mainly with one haplotype, indicating a single, relatively recent origin in Caucasians. This was an individual who lived in northern Europe some 6,000 years ago. Since then, the variant has spread through Europe with a frequency gradient extending from north to south: 5% of Scandinavians, 4% of Britons, 1 to 2% of southern Europeans, and 3% of the heterogeneous white population in the United States are MZ heterozygotes. Curiously, there is a reciprocal distribution of the S variant form: 10% in southern Europe to 5% in the north. As a general rule then, 1 in 10 persons of European origin will be heterozygous for either the S or Z variant, i.e., MZ or MS (<a href="#18" class="mim-tip-reference" title="Carrell, R. W. <strong>Alpha-1-antitrypsin: molecular pathology, leukocytes, and tissue damage.</strong> J. Clin. Invest. 78: 1427-1431, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3537008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3537008</a>] [<a href="https://doi.org/10.1172/JCI112731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3537008">Carrell, 1986</a>). <a href="#84" class="mim-tip-reference" title="Kawakami, Y., Irie, T., Kishi, F., Asanuma, Y., Shida, A., Yoshikawa, T., Kamishima, K., Hasegawa, H., Murao, M. <strong>Familial aggregation of abnormal ventilatory control and pulmonary function in chronic obstructive pulmonary disease.</strong> Europ. J. Resp. Dis. 62: 56-64, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7227484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7227484</a>]" pmid="7227484">Kawakami et al. (1981)</a> cited 2 studies in which no Pi Z was found among 965 healthy Japanese and 183 Japanese with pulmonary diseases. This is to be compared with a frequency of 1.6% for Pi Z among Norwegians. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2989709+7227484+3537008" 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>Crystallographic analysis of alpha-1-antitrypsin predicts that in the normal protein a negatively charged glu342 is adjacent to a positively charged lys290. Thus, the glu342-to-lys Z mutation causes the loss of a normal salt bridge, resulting in intracellular aggregation of the Z molecule. <a href="#11" class="mim-tip-reference" title="Brantly, M., Courtney, M., Crystal, R. G. <strong>Repair of the secretion defect in the Z form of alpha-1-antitrypsin by addition of a second mutation.</strong> Science 242: 1700-1702, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2904702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2904702</a>] [<a href="https://doi.org/10.1126/science.2904702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2904702">Brantly et al. (1988)</a> predicted that a second mutation that changed the positively charged lys290 to a negatively charged glu290 would correct the secretion defect. They demonstrated that such was the case: when the second mutation was added to the Z-type cDNA, the resulting gene directed the synthesis and secretion of AAT similar to that directed by the normal AAT cDNA in an in vitro eukaryotic expression system. In general it may be possible to correct human hereditary disease by inserting an additional mutation in the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2904702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By analyzing nonrecombinant SNPs of 21 Latvian and 65 Swedish heterozygous and homozygous PI Z allele carriers and 113 healthy Latvian controls, <a href="#92" class="mim-tip-reference" title="Lace, B., Sveger, T., Krams, A., Cernevska, G., Krumina, A. <strong>Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis.</strong> Ann. Hum. Genet. 72: 300-304, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18294358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18294358</a>] [<a href="https://doi.org/10.1111/j.1469-1809.2008.00431.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18294358">Lace et al. (2008)</a> estimated the age of the PI Z mutation to be 2,902 years in Latvia and 2,362 years in Sweden. The SNPs showed a high degree of similarity between the 2 populations, indicating a common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18294358" 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>Approximately 3 to 5% of patients with cystic fibrosis (CF; <a href="/entry/219700">219700</a>) develop severe liver disease defined as cirrhosis with portal hypertension. <a href="#4" class="mim-tip-reference" title="Bartlett, J. R., Friedman, K. J., Ling, S. C., Pace, R. G., Bell, S. C., Bourke, B., Castaldo, G., Castellani, C., Cipolli, M., Colombo, C., Colombo, J. L., Debray, D., and 22 others. <strong>Genetic modifiers of liver disease in cystic fibrosis.</strong> JAMA 302: 1076-1083, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19738092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19738092</a>] [<a href="https://doi.org/10.1001/jama.2009.1295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19738092">Bartlett et al. (2009)</a> performed a 2-stage case control study enrolling patients with CF and severe liver disease with portal hypertension from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America. In the first stage, 124 patients with CF and severe liver disease, enrolled between January 1999 and December 2004, and 843 control patients without CF-related liver disease (all assessed at greater than 15 years of age) were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the 2 genes that were positive from the first stage were tested in an additional 136 patients with CF-related liver disease enrolled between January 2005 and February 2007, and in 1,088 with no CF-related liver disease. The combined analysis of the initial and replication studies by logistic regression showed CF-related liver disease to be associated with the SERPINA1 Z allele (odds ratio = 5.04; 95% confidence interval 2.88-8.83; p = 1.5 x 10(-8)). <a href="#4" class="mim-tip-reference" title="Bartlett, J. R., Friedman, K. J., Ling, S. C., Pace, R. G., Bell, S. C., Bourke, B., Castaldo, G., Castellani, C., Cipolli, M., Colombo, C., Colombo, J. L., Debray, D., and 22 others. <strong>Genetic modifiers of liver disease in cystic fibrosis.</strong> JAMA 302: 1076-1083, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19738092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19738092</a>] [<a href="https://doi.org/10.1001/jama.2009.1295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19738092">Bartlett et al. (2009)</a> concluded that the SERPINA1 Z allele is a risk factor for liver disease in CF. Patients carrying the Z allele are at greater risk (odds ratio = approximately 5) of developing severe liver disease with portal hypertension. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19738092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using several markers of ER stress response, <a href="#85" class="mim-tip-reference" title="Kelly, E., Greene, C. M., Carroll, T. P., McElvaney, N. G., O'Neill, S. J. <strong>Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha-1-antitrypsin deficiency.</strong> J. Biol. Chem. 284: 16891-16897, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19398551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19398551</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19398551[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M109.006288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19398551">Kelly et al. (2009)</a> found that expression of AAT with the Z mutation, which they called ZAAT, resulted in ER stress in transfected HepG2 cells. Coexpression of the ER stress response selenoprotein SEPS1 (<a href="/entry/607918">607918</a>) relieved ER stress caused by ZAAT expression or by exposure to tunicamycin, a known ER stressor. Supplementation of cells with selenium augmented the activity of SEPS1. Selenium supplementation also increased endogenous SEPS1 expression and reduced ER stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19398551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using AT01 human liver cells overexpressing GP78, <a href="#87" class="mim-tip-reference" title="Khodayari, N., Wang, R. L., Marek, G., Krotova, K., Kirst, M., Liu, C., Rouhani, F., Brantly, M. <strong>SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78.</strong> PLoS One 12: e0172983, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28301499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28301499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28301499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0172983" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28301499">Khodayari et al. (2017)</a> showed that GP78 (AMFR; <a href="/entry/603243">603243</a>) regulated degradation of ubiquitinated ZAAT. GP78 targeted ZAAT for proteasomal degradation, and GP78 overexpression significantly decreased the level of accumulated ZAAT and caused faster ZAAT clearance from the ER, without significant changes in the level of extracellular ZAAT. This process involved VCP (<a href="/entry/601023">601023</a>), as GP78 interacted with VCP, and the interaction was enhanced in A1ATD liver tissue. SVIP (<a href="/entry/620965">620965</a>) expression was relatively high in A1ATD, and overexpression of SVIP negatively regulated GP78/VCP-mediated ERAD. Knockdown analysis in AT01 cells confirmed that endogenous SVIP negatively regulated GP78 function and inhibited ZAAT degradation. Electron microscopic analysis revealed that SVIP overexpression caused vacuole formation in AT01 cells, which was abrogated by silencing of SVIP. The authors proposed that GP78 overexpression or SVIP suppression may eliminate the toxic gain of function associated with ZAAT polymerization, thus providing a novel therapeutic approach to treatment of A1ATD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28301499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 PI M(MALTON)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, PHE52DEL ON M2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs775982338 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs775982338;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs775982338?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs775982338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs775982338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019568 OR RCV000019572 OR RCV000262058 OR RCV000594562 OR RCV003417992" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019568, RCV000019572, RCV000262058, RCV000594562, RCV003417992" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019568...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Liver disease, as well as emphysema, has been described in patients with the rare PI*M(Malton) allele. <a href="#56" class="mim-tip-reference" title="Fraizer, G. C., Harrold, T. R., Hofker, M. H., Cox, D. W. <strong>In-frame single codon deletion in the M(Malton) deficiency allele of alpha-1-antitrypsin.</strong> Am. J. Hum. Genet. 44: 894-902, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786335</a>]" pmid="2786335">Fraizer et al. (1989)</a> studied the molecular defect in M(Malton), a deficiency allele which, like the Z allele, is associated with hepatocyte inclusions and impairs secretion. They found that the M(Malton) allele contains a deletion of the codon for 1 of the 2 adjacent phenylalanine residues (amino acid 51 or 52 of the mature protein). Judging from the haplotype data, the M(Malton) mutation must have derived from the normal M2 allele. Deletion of the 1 amino acid would be expected to shorten 1 strand of the beta-sheet, B6, apparently preventing normal processing and secretion. <a href="#38" class="mim-tip-reference" title="Curiel, D. T., Holmes, M. D., Okayama, H., Brantly, M. L., Vogelmeier, C., Travis, W. D. <strong>Stier, L. E.; Perks, W. H. and Crystal, R. G.: Molecular basis of the liver and lung disease associated with the alpha-1-antitrypsin deficiency allele M(Malton).</strong> J. Biol. Chem. 264: 13938-13945, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2788166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2788166</a>]" pmid="2788166">Curiel et al. (1989)</a> also showed that the M(Malton) allele differs from the normal M2 allele by deletion of the entire codon (TTC) for residue phe52. They demonstrated abnormal intracellular accumulation of newly synthesized AAT protein in a homozygote who also showed, on liver biopsy, inflammation, mild fibrosis, and intrahepatocyte accumulation of the protein. Furthermore, <a href="#38" class="mim-tip-reference" title="Curiel, D. T., Holmes, M. D., Okayama, H., Brantly, M. L., Vogelmeier, C., Travis, W. D. <strong>Stier, L. E.; Perks, W. H. and Crystal, R. G.: Molecular basis of the liver and lung disease associated with the alpha-1-antitrypsin deficiency allele M(Malton).</strong> J. Biol. Chem. 264: 13938-13945, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2788166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2788166</a>]" pmid="2788166">Curiel et al. (1989)</a> showed by retroviral gene transfer of AAT cDNA with the M(Malton) phe52 deletion into murine cells that abnormal accumulation of the newly synthesized protein occurred. This provides further evidence that abnormal intrahepatocyte AAT accumulation is responsible for the liver injury. By means of gene amplification and direct DNA sequencing, <a href="#67" class="mim-tip-reference" title="Graham, A., Kalsheker, N. A., Newton, C. R., Bamforth, F. J., Powell, S. J., Markham, A. F. <strong>Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null (Cardiff) (asp256-to-val), Pi M(Malton) (phe51-deletion) and Pi I (arg39-to-cys).</strong> Hum. Genet. 84: 55-58, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2606478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2606478</a>] [<a href="https://doi.org/10.1007/BF00210671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2606478">Graham et al. (1989)</a> identified the same mutation, pointing out that it could be either phenylalanine-51 or phenylalanine-52 that is deleted. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2786335+2606478+2788166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 PI S</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLU264VAL ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs17580 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs17580;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs17580?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs17580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs17580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019569 OR RCV000148878 OR RCV000177031 OR RCV000508742 OR RCV000508836 OR RCV000762932 OR RCV000768544 OR RCV000991136 OR RCV001195102 OR RCV002371777 OR RCV002466248 OR RCV003415722" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019569, RCV000148878, RCV000177031, RCV000508742, RCV000508836, RCV000762932, RCV000768544, RCV000991136, RCV001195102, RCV002371777, RCV002466248, RCV003415722" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019569...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#113" class="mim-tip-reference" title="Owen, M. C., Carrell, R. W. <strong>Alpha-1-antitrypsin: molecular abnormality of S variant.</strong> Brit. Med. J. 1: 130-131, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1082356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1082356</a>] [<a href="https://doi.org/10.1136/bmj.1.6002.130-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1082356">Owen and Carrell (1976)</a> and <a href="#141" class="mim-tip-reference" title="Yoshida, A., Ewing, C., Wessels, M., Lieberman, J., Gaidulis, L. <strong>Molecular abnormality of Pi S variant of human alpha-1-antitrypsin.</strong> Am. J. Hum. Genet. 29: 233-239, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/301355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">301355</a>]" pmid="301355">Yoshida et al. (1977)</a> found substitution of valine for glutamic acid at position 264 in the S variant of alpha-1-antitrypsin. See <a href="#98" class="mim-tip-reference" title="Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W., Kurachi, K. <strong>Complete sequence of the cDNA for human alpha-1-antitrypsin and the gene for the S variant.</strong> Biochemistry 23: 4828-4837, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6093867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6093867</a>] [<a href="https://doi.org/10.1021/bi00316a003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6093867">Long et al. (1984)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1082356+301355+6093867" 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="#37" class="mim-tip-reference" title="Curiel, D. T., Chytil, A., Courtney, M., Crystal, R. G. <strong>Serum alpha-1-antitrypsin deficiency associated with the common S-type (glu264-to-val) mutation results from intracellular degradation of alpha-1-antitrypsin prior to secretion.</strong> J. Biol. Chem. 264: 10477-10486, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2567291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2567291</a>]" pmid="2567291">Curiel et al. (1989)</a> concluded that the S-type AAT protein is degraded intracellularly before secretion. PI*S homozygotes are at no risk of emphysema, but compound heterozygotes with Z or a null allele have a mildly increased risk. Because of the high frequency of the PI*S allele (0.02-0.04 in US Caucasians), such compound heterozygotes are relatively frequent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2567291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 PI M(HEERLEN)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, PRO369LEU ON M1A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs199422209 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422209;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs199422209?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199422209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199422209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019565 OR RCV000409001 OR RCV000727230 OR RCV002336088 OR RCV003944831" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019565, RCV000409001, RCV000727230, RCV002336088, RCV003944831" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019565...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#73" class="mim-tip-reference" title="Hofker, M. H., Nukiwa, T., van Paassen, H. M. B., Nelen, M., Kramps, J. A., Klasen, E. C., Frants, R. R., Crystal, R. G. <strong>A pro-to-leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen.</strong> Hum. Genet. 81: 264-268, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2784123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2784123</a>] [<a href="https://doi.org/10.1007/BF00279001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2784123">Hofker et al. (1989)</a> demonstrated the molecular defect in the PI gene of a patient with a serum level of only 5 mg/100 ml and a PI M-like phenotype, designated PI M(Heerlen). They demonstrated a substitution of leucine for proline at codon 369, which resulted from a C-to-T mutation in exon 5. Otherwise the nucleotide sequence of the exons, intron/exon junctions, and a part of the promoter region was similar to that of a PI M1(ala213) gene. <a href="#82" class="mim-tip-reference" title="Kalsheker, N., Hayes, K., Weidinger, S., Graham, A. <strong>What is Pi (proteinase inhibitor) null or PiQ0? A problem highlighted by the alpha-1-antitrypsin M(Heerlen) mutation.</strong> J. Med. Genet. 29: 27-29, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1552539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1552539</a>] [<a href="https://doi.org/10.1136/jmg.29.1.27" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1552539">Kalsheker et al. (1992)</a> described a family with Pi M(Heerlen) and commented on the difficulties of diagnosis of rare PI (null) or Q0 variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1552539+2784123" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 PI M(MINERAL SPRINGS)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLY67GLU ON M1A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28931568 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931568;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28931568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28931568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019566 OR RCV000201855" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019566, RCV000201855" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019566...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This mutation, which causes AAT deficiency and emphysema, is unique among antitrypsin mutations in that it was observed in a black family, whereas most mutations causing AAT deficiency are confined to Caucasian populations of European descent. The index case was homozygous. A GGG-to-GAG change in codon 67 led to substitution of glutamic acid for glycine (<a href="#39" class="mim-tip-reference" title="Curiel, D. T., Vogelmeier, C., Hubbard, R. C., Stier, L. E., Crystal, R. G. <strong>Molecular basis of alpha-1-antitrypsin deficiency and emphysema associated with the alpha-1-antitrypsin M(Mineral Springs) allele.</strong> Molec. Cell. Biol. 10: 47-56, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967187</a>] [<a href="https://doi.org/10.1128/mcb.10.1.47-56.1990" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1967187">Curiel et al., 1990</a>). <a href="#39" class="mim-tip-reference" title="Curiel, D. T., Vogelmeier, C., Hubbard, R. C., Stier, L. E., Crystal, R. G. <strong>Molecular basis of alpha-1-antitrypsin deficiency and emphysema associated with the alpha-1-antitrypsin M(Mineral Springs) allele.</strong> Molec. Cell. Biol. 10: 47-56, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967187</a>] [<a href="https://doi.org/10.1128/mcb.10.1.47-56.1990" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1967187">Curiel et al. (1990)</a> showed that this mutation caused reduced AAT secretion on the basis of aberrant posttranslational biosynthesis by a mechanism distinct from that associated with the Z allele, whereby intracellular aggregation of the mutant protein is responsible for the secretory defect. Furthermore, the M(Mineral Springs) mutation markedly affected the ability of the protein that did reach the circulation to inhibit neutrophil elastase. Homozygotes have a high risk of emphysema (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1967187+2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 PI M(PROCIDA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, LEU41PRO ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28931569 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931569;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28931569?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28931569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28931569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019571 OR RCV000201848 OR RCV000729804 OR RCV004584332" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019571, RCV000201848, RCV000729804, RCV004584332" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019571...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#130" class="mim-tip-reference" title="Takahashi, H., Nukiwa, T., Satoh, K., Ogushi, F., Brantly, M., Fells, G., Stier, L., Courtney, M., Crystal, R. G. <strong>Characterization of the gene and protein of the alpha-1-antitrypsin 'deficiency' allele M(procida).</strong> J. Biol. Chem. 263: 15528-15534, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262617</a>]" pmid="3262617">Takahashi et al. (1988)</a> showed that M(Procida) has a substitution of proline for leucine at position 41, resulting from a change of codon CTG to CCG. The rare mutant protein shows somewhat reduced catalytic activity; its concentration is low in plasma, apparently because of instability and resulting intracellular degradation before secretion. Homozygotes have a high risk of emphysema (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2696185+3262617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 PI M(NICHINAN)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, PHE52DEL AND GLY148ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs112030253 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs112030253;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs112030253?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs112030253" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs112030253" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019568 OR RCV000019572 OR RCV000262058 OR RCV000512621 OR RCV000594562 OR RCV000597384 OR RCV003417992" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019568, RCV000019572, RCV000262058, RCV000512621, RCV000594562, RCV000597384, RCV003417992" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019568...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#105" class="mim-tip-reference" title="Nakamura, H., Ogawa, A., Hisano, S., Fukuma, M., Tachibana, N., Tsuda, K. <strong>A family with a new deficient variant of alpha-1-antitrypsin PiM(Nichinan): with special reference to diastase-resistant, periodic acid-Schiff positive globules in the liver cells.</strong> J. Jpn. Soc. Intern. Med. 69: 47-54, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6162902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6162902</a>] [<a href="https://doi.org/10.2169/naika.69.967" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6162902">Nakamura et al. (1980)</a> found this variant in a 42-year-old Japanese woman with neither pulmonary emphysema nor liver dysfunction. She was the product of a consanguineous marriage. Radial immunodiffusion assay showed a low level of AAT in serum (17.9 mg/dl as compared to the normal range of 190-280 mg/dl). Aggregation of AAT molecules was demonstrated histologically in hepatocytes, indicating profound reduction in the secretion of the protein. Serum AAT levels in the members of the family demonstrated that the proband was homozygous for the M(Nichinan) allele. <a href="#102" class="mim-tip-reference" title="Matsunaga, E., Shiokawa, S., Nakamura, H., Maruyama, T., Tsuda, K., Fukumaki, Y. <strong>Molecular analysis of the gene of the alpha-1-antitrypsin deficiency variant, M(Nichinan).</strong> Am. J. Hum. Genet. 46: 602-612, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309708</a>]" pmid="2309708">Matsunaga et al. (1990)</a> demonstrated that the M(Nichinan) gene is identical with the M1(val213) gene except for 2 changes: a TTC trinucleotide deletion in the codon for phenylalanine-52 and a G-A substitution by which the normal gly148(GGG) became arg148(AGG). <a href="#102" class="mim-tip-reference" title="Matsunaga, E., Shiokawa, S., Nakamura, H., Maruyama, T., Tsuda, K., Fukumaki, Y. <strong>Molecular analysis of the gene of the alpha-1-antitrypsin deficiency variant, M(Nichinan).</strong> Am. J. Hum. Genet. 46: 602-612, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309708</a>]" pmid="2309708">Matsunaga et al. (1990)</a> suggested that the gly148-to-arg change is unlikely to be the cause of the AAT deficiency because arg (not gly) is located at the corresponding position of the protein C inhibitor which belongs to the same family of serine protease. On the other hand, <a href="#102" class="mim-tip-reference" title="Matsunaga, E., Shiokawa, S., Nakamura, H., Maruyama, T., Tsuda, K., Fukumaki, Y. <strong>Molecular analysis of the gene of the alpha-1-antitrypsin deficiency variant, M(Nichinan).</strong> Am. J. Hum. Genet. 46: 602-612, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309708</a>]" pmid="2309708">Matsunaga et al. (1990)</a> suggested that deletion of phenylalanine-52 may cause the newly synthesized AAT protein to aggregate, resulting in serum AAT deficiency. They suggested that the gly148-to-arg substitution reflects the vulnerability of a CpG dinucleotide to mutation. They pointed to a number of other variant forms of AAT that were probably generated through a C-T transition. Indeed, the Z and M1(val213) genes were generated from the M1(ala213) gene by the C-T transition at the CpG dinucleotide on the antisense and the sense strands, respectively. The M2 gene was generated from the M3 gene by the same mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6162902+2309708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 PI I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ARG39CYS ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28931570 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931570;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28931570?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28931570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28931570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019575 OR RCV000148875 OR RCV000205893 OR RCV000431149 OR RCV003390693" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019575, RCV000148875, RCV000205893, RCV000431149, RCV003390693" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019575...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By gene amplification and direct DNA sequencing, <a href="#67" class="mim-tip-reference" title="Graham, A., Kalsheker, N. A., Newton, C. R., Bamforth, F. J., Powell, S. J., Markham, A. F. <strong>Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null (Cardiff) (asp256-to-val), Pi M(Malton) (phe51-deletion) and Pi I (arg39-to-cys).</strong> Hum. Genet. 84: 55-58, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2606478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2606478</a>] [<a href="https://doi.org/10.1007/BF00210671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2606478">Graham et al. (1989)</a> identified this mutation, CGC to TGC, in a compound heterozygote. Homozygotes are at no risk of emphysema, but compound heterozygotes with Z or a null allele have a mildly increased risk (<a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal, 1989</a>). In 1 individual and 3 independent families, <a href="#125" class="mim-tip-reference" title="Seri, M., Magi, B., Cellesi, C., Olia, P. M., Renieri, A., De Marchi, M. <strong>Molecular characterization of the P and I variants of alpha-1-antitrypsin.</strong> Int. J. Clin. Lab. Res. 22: 119-121, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1504305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1504305</a>] [<a href="https://doi.org/10.1007/BF02591409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1504305">Seri et al. (1992)</a> confirmed that the I variant resulted from a CGC (arg)-to-TGC (cys) transition at codon 39 within exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2696185+2606478+1504305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 PI P(LOWELL)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI NULL(CARDIFF)<br />
|
|
PI Q0(CARDIFF)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ASP256VAL ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912714 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912714;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912714?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019576 OR RCV000019577 OR RCV000019578 OR RCV000019605 OR RCV000148876 OR RCV000398063 OR RCV003415723" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019576, RCV000019577, RCV000019578, RCV000019605, RCV000148876, RCV000398063, RCV003415723" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019576...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#45" class="mim-tip-reference" title="Faber, J. P., Weidinger, S., Goedde, H.-W., Olek, K. <strong>The deficient alpha-1-antitrypsin phenotype Pi P is associated with an A-to-T transversion in exon III of the gene. (Letter)</strong> Am. J. Hum. Genet. 45: 161-163, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2787118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2787118</a>]" pmid="2787118">Faber et al. (1989)</a> demonstrated that this rare allele, a cause of deficiency of alpha-1-antitrypsin, results from an A-to-T transversion in exon 3 of the gene. As a result, GAT (aspartic acid at residue 256) is converted to GTT (valine at that position). The same change was found in a total of 4 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2787118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By gene amplification and direct DNA sequencing, <a href="#67" class="mim-tip-reference" title="Graham, A., Kalsheker, N. A., Newton, C. R., Bamforth, F. J., Powell, S. J., Markham, A. F. <strong>Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null (Cardiff) (asp256-to-val), Pi M(Malton) (phe51-deletion) and Pi I (arg39-to-cys).</strong> Hum. Genet. 84: 55-58, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2606478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2606478</a>] [<a href="https://doi.org/10.1007/BF00210671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2606478">Graham et al. (1989)</a> identified the same mutation in a variant they called Null(Cardiff). According to the tabulation by <a href="#34" class="mim-tip-reference" title="Crystal, R. G. <strong>The alpha-1-antitrypsin gene and its deficiency states.</strong> Trends Genet. 5: 411-417, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>] [<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2696185">Crystal (1989)</a>, homozygotes have no risk for emphysema, but compound heterozygotes with a Z or null allele have a mildly increased risk. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2696185+2606478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By retroviral insertion of the P(Lowell) cDNA into the genome of NIH-3T3 fibroblasts, <a href="#74" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Crystal, R. G. <strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong> Am. Rev. Resp. Dis. 142: 1185-1192, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2240842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2240842</a>] [<a href="https://doi.org/10.1164/ajrccm/142.5.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2240842">Holmes et al. (1990)</a> demonstrated a pattern of biosynthesis of AAT consistent with the intracellular degradation of newly synthesized protein. Because serum AAT deficiency associated with other mutations resulting from intracellular degradation of the protein can be overcome by administration of estrogenlike drugs, <a href="#74" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Crystal, R. G. <strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong> Am. Rev. Resp. Dis. 142: 1185-1192, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2240842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2240842</a>] [<a href="https://doi.org/10.1164/ajrccm/142.5.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2240842">Holmes et al. (1990)</a> administered tamoxifen to a subject with the P(Lowell)/Z phenotype and demonstrated a 48% rise in AAT serum levels over a 5-month period, from below the threshold for protection from emphysema to a value above that threshold. <a href="#125" class="mim-tip-reference" title="Seri, M., Magi, B., Cellesi, C., Olia, P. M., Renieri, A., De Marchi, M. <strong>Molecular characterization of the P and I variants of alpha-1-antitrypsin.</strong> Int. J. Clin. Lab. Res. 22: 119-121, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1504305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1504305</a>] [<a href="https://doi.org/10.1007/BF02591409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1504305">Seri et al. (1992)</a> confirmed the nature of the mutation in P(Lowell). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2240842+1504305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#71" class="mim-tip-reference" title="Hildesheim, J., Kinsley, G., Bissell, M., Pierce, J., Brantly, M. <strong>Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha-1-antitrypsin deficiency variant P(Duarte).</strong> Hum. Mutat. 2: 221-228, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364590</a>] [<a href="https://doi.org/10.1002/humu.1380020311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8364590">Hildesheim et al. (1993)</a> demonstrated that P(Duarte) (<a href="#0037">107400.0037</a>) has the same mutation as that in P(Lowell) but that it is on a background of the normal M4 allele (R101H; <a href="#0005">107400.0005</a>). <a href="#71" class="mim-tip-reference" title="Hildesheim, J., Kinsley, G., Bissell, M., Pierce, J., Brantly, M. <strong>Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha-1-antitrypsin deficiency variant P(Duarte).</strong> Hum. Mutat. 2: 221-228, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364590</a>] [<a href="https://doi.org/10.1002/humu.1380020311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8364590">Hildesheim et al. (1993)</a> pointed out that this is an example of genetic diversity resulting from a limited repertoire of mutations on different common allelic backgrounds--a combinatorial basis for genetic diversity. A similar example is the occurrence of Creutzfeldt-Jakob disease and fatal familial insomnia as a result of the same mutation, depending on the nature of a nucleotide polymorphism at another site in the prion protein gene (PRNP; <a href="/entry/176640#0010">176640.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8364590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 PI NULL(GRANITE FALLS)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(GRANITE FALLS)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, TYR160TER ON M1A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267606950 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606950;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs267606950?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019579 OR RCV000019580" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019579, RCV000019580" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019579...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The gene shows deletion of the third nucleotide in the tyr160 codon TAC, causing a frameshift with new stop codon TAG at position 160 (<a href="#109" class="mim-tip-reference" title="Nukiwa, T., Takahashi, H., Brantly, M., Courtney, M., Crystal, R. G. <strong>Alpha-1-antitrypsin null (Granite Falls), a nonexpressing alpha-1-antitrypsin gene associated with a frameshift to stop mutation in a coding exon.</strong> J. Biol. Chem. 262: 11999-12004, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3040726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3040726</a>]" pmid="3040726">Nukiwa et al., 1987</a>). Emphysema is associated with homozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3040726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 PI NULL(BELLINGHAM)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(BELLINGHAM)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, LYS217TER ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs199422211 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422211;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs199422211?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199422211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199422211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019581 OR RCV000019582 OR RCV000169162 OR RCV001528835" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019581, RCV000019582, RCV000169162, RCV001528835" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019581...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By cloning and sequencing the Null(Bellingham) gene (which in homozygous state is associated with early-onset emphysema), <a href="#119" class="mim-tip-reference" title="Satoh, K., Nukiwa, T., Brantly, M., Garver, R. I., Jr., Hofker, M., Courtney, M., Crystal, R. G. <strong>Emphysema associated with complete absence of alpha-1-antitrypsin in serum and the homozygous inheritance of a stop codon in an alpha-1-antitrypsin-coding exon.</strong> Am. J. Hum. Genet. 42: 77-83, 1988. Note: Erratum: Am. J. Hum. Genet. 42: 789 only, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3257351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3257351</a>]" pmid="3257351">Satoh et al. (1988)</a> demonstrated that the promoter region, coding exons, and all exon-intron junctions are normal except for a single base substitution in exon 3, which causes the normal lys217 (AAG) to become a stop codon (TAG). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3257351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 PI NULL(MATTAWA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, LEU353PHE ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28929473 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28929473;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28929473?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28929473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28929473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019583" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019583" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019583</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#24" class="mim-tip-reference" title="Cox, D. W., Levison, H. <strong>Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes).</strong> Am. Rev. Respir. Dis. 137: 371-375, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3257661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3257661</a>] [<a href="https://doi.org/10.1164/ajrccm/137.2.371" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3257661">Cox and Levison (1988)</a> reported a family in which several members manifested no detectable plasma alpha-1-antitrypsin (<a href="/entry/613490">613490</a>), indicating a 'null' AAT allele, which the authors designated Null Mattawa (QO-Mattawa). <a href="#36" class="mim-tip-reference" title="Curiel, D., Brantly, M., Curiel, E., Stier, L., Crystal, R. G. <strong>Alpha-1-antitrypsin deficiency caused by the alpha-1-antitrypsin null(Mattawa) gene: an insertion mutation rendering the alpha-1-antitrypsin gene incapable of producing alpha-1-antitrypsin.</strong> J. Clin. Invest. 83: 1144-1152, 1989. Note: Erratum: J. Clin. Invest. 84: following 1041, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2539391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2539391</a>] [<a href="https://doi.org/10.1172/JCI113994" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2539391">Curiel et al. (1989)</a> studied 2 affected sisters in this family and found that they were compound heterozygous for 2 mutations in the AAT gene: Null(Bellingham) (<a href="#0021">107400.0021</a>) and Null(Mattawa). Sequencing of exons 1c-5 and all exon-intron junctions of the Null(Mattawa) gene demonstrated that it was identical to the common normal M1(val213) gene except for the insertion of a single nucleotide within the coding region of exon 5, causing a 3-prime frameshift with generation of a premature stop signal at position 376. Monocytes were shown to have an mRNA transcript of normal size, and in vitro translation showed that the mRNA was translated at a normal rate but produced a truncated antitrypsin protein. Additionally, retroviral transfer of the cDNA to murine fibroblasts demonstrated no detectable intracellular or secreted protein despite the presence of Null(Mattawa) mRNA. Thus, the molecular pathophysiology of Null(Mattawa) is probably manifested at a posttranslational level. This allele is associated with high risk of emphysema. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2539391+3257661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 PI NULL(PROCIDA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI NULL(ISOLA DI PROCIDA)<br />
|
|
PI Q0(PROCIDA)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, 17-KB DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019584 OR RCV000203601" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019584, RCV000203601" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019584...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Of the 5 previously known representatives of the 'null' group of AAT-deficient alleles (i.e., genes incapable of producing AAT protein detectable in serum) evaluated at the gene level, all had stop codons in coding exons. Cloning and mapping of the Null(Isola di Procida) gene demonstrated deletion of a 17-kb fragment that included exons 2-5 of the AAT structural gene (<a href="#129" class="mim-tip-reference" title="Takahashi, H., Crystal, R. G. <strong>Alpha-1-antitrypsin Null(Isola di Procida): an alpha-1-antitrypsin deficiency allele caused by deletion of all alpha-1-antitrypsin coding exons.</strong> Am. J. Hum. Genet. 47: 403-413, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975477</a>]" pmid="1975477">Takahashi and Crystal, 1990</a>). Sequence analysis showed a 7-bp repeat sequence both 5-prime to the deletion and at the 3-prime end of the deletion, suggesting that the mechanism of the deletion may have been a slipped mispairing. This mutation, which at first was called Null(Procida), was found in heterozygous state with the M(Procida) allele (<a href="#0016">107400.0016</a>) reported by <a href="#130" class="mim-tip-reference" title="Takahashi, H., Nukiwa, T., Satoh, K., Ogushi, F., Brantly, M., Fells, G., Stier, L., Courtney, M., Crystal, R. G. <strong>Characterization of the gene and protein of the alpha-1-antitrypsin 'deficiency' allele M(procida).</strong> J. Biol. Chem. 263: 15528-15534, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262617</a>]" pmid="3262617">Takahashi et al. (1988)</a>. To avoid confusion with M(Procida), Null(Procida) was renamed Null(Isola di Procida). This mutation is associated with high risk of emphysema. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1975477+3262617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 PI NULL(HONG KONG 1)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(HONG KONG 1)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, 2-BP DEL, FS334TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057519610 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519610;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1057519610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1057519610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019587 OR RCV000019588 OR RCV000201857" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019587, RCV000019588, RCV000201857" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019587...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Deletion of TC from CTC codon 318 for leucine causes frameshift with stop codon TAA at position 334. Homozygosity for this allele, like other null alleles, predisposes to early-onset emphysema. See <a href="#127" class="mim-tip-reference" title="Sifers, R. N., Brashears-Macatee, S., Kidd, V. J., Muensch, H., Woo, S. L. C. <strong>A frameshift mutation results in a truncated alpha-1-antitrypsin that is retained within the rough endoplasmic reticulum.</strong> J. Biol. Chem. 263: 7330-7335, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259232</a>]" pmid="3259232">Sifers et al. (1988)</a>. This variant was initially called Null(Hong Kong) but later Null(Hong Kong-1) because a second null allele called Null(Hong Kong-2) (<a href="#0034">107400.0034</a>) was identified in the same individual by haplotype analysis (<a href="#57" class="mim-tip-reference" title="Fraizer, G. C., Siewertsen, M. A., Hofker, M. H., Brubacher, M. G., Cox, D. W. <strong>A null deficiency allele of alpha-1-antitrypsin, Q0-Ludwigshafen, with altered tertiary structure.</strong> J. Clin. Invest. 86: 1878-1884, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2254451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2254451</a>] [<a href="https://doi.org/10.1172/JCI114919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2254451">Fraizer et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3259232+2254451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 PI NULL(BOLTON)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(BOLTON)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, 1-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs764325655 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs764325655;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs764325655?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs764325655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs764325655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019589 OR RCV000019590 OR RCV000512620" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019589, RCV000019590, RCV000512620" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019589...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#58" class="mim-tip-reference" title="Fraizer, G. C., Siewertsen, M., Harold, T. R., Cox, D. W. <strong>Deletion/frameshift mutation in the alpha-1-antitrypsin null allele, PI*Q0(Bolton).</strong> Hum. Genet. 83: 377-382, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2807278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2807278</a>] [<a href="https://doi.org/10.1007/BF00291385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2807278">Fraizer et al. (1989)</a> observed a unique PI null allele. By cloning and sequencing the allele, they demonstrated deletion of a single cytosine residue (the third C in the CCC codon 362 for proline) near the active site of alpha-1-antitrypsin in exon 5 resulting in a frameshift which caused an in-frame stop codon downstream of the deletion. The stop codon led to premature termination of protein translation at amino acid 373, resulting in a truncated protein. PI Q0(Bolton) was observed in combination with PI*M(Malton) in 2 compound heterozygotes. The allele carries a high risk of emphysema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2807278" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 PI PITTSBURGH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
'ANTITHROMBIN' PITTSBURGH
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, MET358ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912713 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912713;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912713?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019591 OR RCV000201860" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019591, RCV000201860" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019591...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This structure mutation in the PI gene alters its function such that it becomes an antithrombin and leads to a bleeding disorder. Alpha-1-antitrypsin and antithrombin III (<a href="/entry/107300">107300</a>) have a similar structure reflecting origin from a common ancestral protein some 500 million years ago. Both are inhibitors of proteolytic enzymes but have different specificities. Alpha-1-antitrypsin protects the body against released elastase, whereas AT III controls coagulation by inhibiting thrombin and other activated coagulation factors. <a href="#111" class="mim-tip-reference" title="Owen, M. C., Brennan, S. O., Lewis, J. H., Carrell, R. W. <strong>Mutation of antitrypsin to antithrombin: alpha-1-antitrypsin Pittsburgh (358 met-to-arg), a fatal bleeding disorder.</strong> New Eng. J. Med. 309: 694-698, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6604220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6604220</a>] [<a href="https://doi.org/10.1056/NEJM198309223091203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6604220">Owen et al. (1983)</a> described a mutation of alpha-1-antitrypsin that converts it to an antithrombin. Whereas synthesis of alpha-1-antitrypsin increases in response to trauma, AT III remains at a constant plasma concentration and requires activation by heparin. The antithrombin activity of the mutant alpha-1-antitrypsin was independent of heparin but its synthesis was stimulated by trauma. The patient was a 14-year-old boy who died in 1981 with a huge hematoma of his leg and abdomen. This was the last of a lifelong series of bleeding episodes occurring after trauma and requiring hospitalization on more than 50 occasions. <a href="#96" class="mim-tip-reference" title="Lewis, J. H., Iammarino, R. M., Spero, J. A., Hasiba, U. <strong>Antithrombin Pittsburgh: an alpha-1-antitrypsin variant causing hemorrhagic disease.</strong> Blood 51: 129-137, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/412531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">412531</a>]" pmid="412531">Lewis et al. (1978)</a> described the clinical picture and identified a variant 'antithrombin' which they called antithrombin Pittsburgh. It had, however, the electrophoretic and antigenic characteristics of a variant alpha-1-antitrypsin. <a href="#111" class="mim-tip-reference" title="Owen, M. C., Brennan, S. O., Lewis, J. H., Carrell, R. W. <strong>Mutation of antitrypsin to antithrombin: alpha-1-antitrypsin Pittsburgh (358 met-to-arg), a fatal bleeding disorder.</strong> New Eng. J. Med. 309: 694-698, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6604220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6604220</a>] [<a href="https://doi.org/10.1056/NEJM198309223091203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6604220">Owen et al. (1983)</a> showed that the variant protein has arginine at position 358, replacing the normal methionine. This finding indicated that the reactive center of alpha-1-antitrypsin is methionine 358, which acts as a 'bait' for elastase, just as the normal reactive center of AT III is arginine-393, which acts as a bait for thrombin. Neutrophils augment tissue proteolysis by the oxidative inactivation of the methionine at the reactive center of alpha-1-antitrypsin. <a href="#122" class="mim-tip-reference" title="Scott, C. F., Carrell, R. W., Glaser, C. B., Kueppers, F., Lewis, J. H., Colman, R. W. <strong>Alpha-1-antitrypsin-Pittsburgh: a potent inhibitor of human plasma factor XIa, kallikrein, and factor XII.</strong> J. Clin. Invest. 77: 631-634, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484755</a>] [<a href="https://doi.org/10.1172/JCI112346" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3484755">Scott et al. (1986)</a> and <a href="#120" class="mim-tip-reference" title="Schapira, M., Ramus, M.-A., Jallat, S., Carvallo, D., Courtney, M. <strong>Recombinant alpha-1-antitrypsin Pittsburgh (met-358 to arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment.</strong> J. Clin. Invest. 77: 635-637, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484756</a>] [<a href="https://doi.org/10.1172/JCI112347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3484756">Schapira et al. (1986)</a> found that recombinant AAT-Pittsburgh (met358-to-arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment, although it has lost its anti-elastase activity. They suggested it might have therapeutic potential in hereditary angioedema or septic shock. <a href="#133" class="mim-tip-reference" title="Vidaud, D., Emmerich, J., Alhenc-Gelas, M., Yvart, J., Fiessinger, J. N., Aiach, M. <strong>Met358-to-arg mutation of alpha-1-antitrypsin associated with protein C deficiency in a patient with mild bleeding tendency.</strong> J. Clin. Invest. 89: 1537-1543, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569192</a>] [<a href="https://doi.org/10.1172/JCI115746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1569192">Vidaud et al. (1992)</a> demonstrated that a G-to-T transversion at nucleotide 10038 is responsible for the substitution of arg for met, which converts alpha-1-antitrypsin into an arg-ser protease inhibitor (serpin) that inhibits thrombin and factor Xa more effectively than antithrombin III. They observed a 15-year-old boy who surprisingly had no bleeding history. They suggested that a large decrease in protein C concentration may account for the mild or absent bleeding tendency. The deficiency of protein C in turn was attributed to deleterious effect of the abnormal inhibitor on both intracellular processing and catabolism of protein C. In later studies, <a href="#43" class="mim-tip-reference" title="Emmerich, J., Alhenc-Gelas, M., Gandrille, S., Guichet, C., Fiessinger, J.-N., Aiach, M. <strong>Mechanism of protein C deficiency in a patient with arginine 358 alpha(1)-antitrypsin (Pittsburgh mutation): role in the maintenance of hemostatic balance.</strong> J. Lab. Clin. Med. 125: 531-539, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7706910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7706910</a>]" pmid="7706910">Emmerich et al. (1995)</a> suggested that strong affinity of the mutant AAT for protein C leads in the patient of <a href="#133" class="mim-tip-reference" title="Vidaud, D., Emmerich, J., Alhenc-Gelas, M., Yvart, J., Fiessinger, J. N., Aiach, M. <strong>Met358-to-arg mutation of alpha-1-antitrypsin associated with protein C deficiency in a patient with mild bleeding tendency.</strong> J. Clin. Invest. 89: 1537-1543, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569192</a>] [<a href="https://doi.org/10.1172/JCI115746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1569192">Vidaud et al. (1992)</a> to an increased turnover and thus to a low circulating level of protein C. They proposed that in the presence of the Pittsburgh mutant protein C can be activated and is abnormally rapidly cleared. The resultant relative lack of protein C anticoagulant function may ameliorate the bleeding diathesis expected to be associated with the Pittsburgh mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=412531+7706910+3484755+1569192+3484756+6604220" 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="#138" class="mim-tip-reference" title="Wilkie, A. O. M. <strong>The molecular basis of genetic dominance.</strong> J. Med. Genet. 31: 89-98, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8182727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8182727</a>] [<a href="https://doi.org/10.1136/jmg.31.2.89" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8182727">Wilkie (1994)</a> discussed the molecular basis of genetic dominance and provided a useful table. He indicated altered substrate specificity as one mechanism and antithrombin Pittsburgh as a specific example. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8182727" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 PI V(MUNICH)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ASP2ALA ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs199422212 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422212;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs199422212?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199422212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199422212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019593 OR RCV000512626" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019593, RCV000512626" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019593...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an alpha-1-antitrypsin variant called V(Munich) because the major fraction focused in the 'V' region of the isoelectric focusing gel, <a href="#74" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Crystal, R. G. <strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong> Am. Rev. Resp. Dis. 142: 1185-1192, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2240842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2240842</a>] [<a href="https://doi.org/10.1164/ajrccm/142.5.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2240842">Holmes et al. (1990)</a> found that the molecule differs from that of the common M1V allele by a single nucleotide substitution of cytosine for adenosine, with the resultant amino acid change asp2 to ala; the codon change is GAT to GCT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2240842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 PI Z(AUGSBURG)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Z(TUN)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLU342LYS ON M2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019567 OR RCV000019594 OR RCV000019595 OR RCV000148877 OR RCV000194811 OR RCV000255454 OR RCV000623762 OR RCV000768543 OR RCV001195107 OR RCV002054450 OR RCV002251912 OR RCV002276567 OR RCV002466247 OR RCV003415721" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019567, RCV000019594, RCV000019595, RCV000148877, RCV000194811, RCV000255454, RCV000623762, RCV000768543, RCV001195107, RCV002054450, RCV002251912, RCV002276567, RCV002466247, RCV003415721" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019567...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Using isoelectric focusing with a narrow pH gradient, <a href="#134" class="mim-tip-reference" title="Weidinger, S., Jahn, W., Cujnik, F., Schwarzfischer, F. <strong>Alpha-1-antitrypsin: evidence for a fifth PI M subtype and a new deficiency allele PI*Z(Augsburg).</strong> Hum. Genet. 71: 27-29, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3875547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3875547</a>] [<a href="https://doi.org/10.1007/BF00295662" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3875547">Weidinger et al. (1985)</a> recognized a rare deficient PI variant, which they called PI Z(Augsburg). To their surprise, <a href="#47" class="mim-tip-reference" title="Faber, J.-P., Weidinger, S., Olek, K. <strong>Sequence data of the rare deficient alpha-1-antitrypsin variant PI Z(Augsburg).</strong> Am. J. Hum. Genet. 46: 1158-1162, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339709</a>]" pmid="2339709">Faber et al. (1990)</a> found that the sequence of the Z(Augsburg) gene showed the common PI*Z mutation (M1 glu342 GAG to Z lys342 AAG) which occurred, however, in an M2 ancestral gene. Previous findings indicated that the Z mutation had always been derived from an M1 ala213 background gene. <a href="#137" class="mim-tip-reference" title="Whitehouse, D. B., Abbott, C. M., Lovegrove, J. U., McIntosh, I., McMahon, C. J., Mieli-Vergani, G., Mowat, A. P., Hopkinson, D. A. <strong>Genetic studies on a new deficiency gene (PI*Z-Tun) at the PI locus.</strong> J. Med. Genet. 26: 744-749, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2575668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2575668</a>] [<a href="https://doi.org/10.1136/jmg.26.12.744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2575668">Whitehouse et al. (1989)</a> studied 2 sibs with mild liver abnormality who were found to be compound heterozygotes for the classical PI*Z allele and an allele that they called PI*Z(Tun). The Z(Tun) protein appeared to be deficient in the plasma to about the same degree as the Z protein. They found that the mutation was precisely the same as that in the Z allele, namely, a G-to-A transition at codon 342 resulting in the substitution of lysine for glutamic acid; however, the Z(Tun) mutation had occurred on an M2-like haplotype background rather than the M1A background. Because of its association with a unique DNA haplotype and the gene frequency estimates in populations of European origin, the Z mutation is thought to have occurred only once, about 6,000 years ago, in a North European person. The Z gene is very rare among other ethnic groups. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2339709+3875547+2575668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 PI W(BETHESDA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ALA336THR ON M1A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1802959 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1802959;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1802959?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1802959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1802959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019596 OR RCV000512619 OR RCV000734987" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019596, RCV000512619, RCV000734987" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019596...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant allele, which is associated with increased risk of emphysema and liver disease, has a mutation in exon 5 where codon 336 is changed from GCT to ACT, resulting in substitution of threonine for alanine (<a href="#35" class="mim-tip-reference" title="Crystal, R. G. <strong>Alpha-1-antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy.</strong> J. Clin. Invest. 85: 1343-1352, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2185272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2185272</a>] [<a href="https://doi.org/10.1172/JCI114578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2185272">Crystal, 1990</a>). <a href="#74" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Crystal, R. G. <strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong> Am. Rev. Resp. Dis. 142: 1185-1192, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2240842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2240842</a>] [<a href="https://doi.org/10.1164/ajrccm/142.5.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2240842">Holmes et al. (1990)</a> reported that the W(Bethesda) form differs from the normal M1(ala-213) allele by a change in codon 336 from GCT to ACT. Although W(Bethesda) mRNA was translated normally in vitro, transfection of the W(Bethesda) cDNA into COS-I cells was associated with AAT secretion only 50% that of cells transfected with normal cDNA. There was no intracellular accumulation as observed with the Z allele, but reduced intracellular AAT suggested degradation of newly synthesized W(Bethesda) molecules. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2185272+2240842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0030" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 PI NULL(DEVON)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(DEVON)<br />
|
|
PI NULL(NEWPORT)<br />
|
|
PI Q0(NEWPORT)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, GLY115SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs11558261 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11558261;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs11558261?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs11558261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs11558261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019597 OR RCV000019598 OR RCV000019599 OR RCV000019600 OR RCV000512622" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019597, RCV000019598, RCV000019599, RCV000019600, RCV000512622" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019597...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, which is associated with increased risk of emphysema and liver disease, is due to a change in exon 2, resulting in substitution of serine for glycine-115 (<a href="#35" class="mim-tip-reference" title="Crystal, R. G. <strong>Alpha-1-antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy.</strong> J. Clin. Invest. 85: 1343-1352, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2185272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2185272</a>] [<a href="https://doi.org/10.1172/JCI114578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2185272">Crystal, 1990</a>). In a compound heterozygote carrying the common disease-producing mutation Pi Z (<a href="#0011">107400.0011</a>), <a href="#65" class="mim-tip-reference" title="Graham, A., Hayes, K., Weidinger, S., Newton, C. R., Markham, A. F., Kalsheker, N. A. <strong>Characterisation of the alpha-1-antitrypsin M3 gene, a normal variant.</strong> Hum. Genet. 85: 381-382, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2394452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2394452</a>] [<a href="https://doi.org/10.1007/BF00206766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2394452">Graham et al. (1990)</a> found a substitution of glycine-115 by serine. The mutation occurred on the background of M3. A change in codon 115 from GGC to AGC was responsible. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2185272+2394452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0031" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 PI NULL(LUDWIGSHAFEN)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(LUDWIGSHAFEN)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ILE92ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28931572 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931572;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28931572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28931572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019601 OR RCV000019602 OR RCV000201851" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019601, RCV000019602, RCV000201851" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019601...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In this variant, which is associated with increased risk of emphysema and liver disease, a change in codon 92 from ATC to AAC in exon 2 results in substitution of asparagine for isoleucine (<a href="#35" class="mim-tip-reference" title="Crystal, R. G. <strong>Alpha-1-antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy.</strong> J. Clin. Invest. 85: 1343-1352, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2185272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2185272</a>] [<a href="https://doi.org/10.1172/JCI114578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2185272">Crystal, 1990</a>). This substitution of a polar for a nonpolar amino acid occurs in 1 of the alpha-helices and is predicted to disrupt the tertiary structure (<a href="#57" class="mim-tip-reference" title="Fraizer, G. C., Siewertsen, M. A., Hofker, M. H., Brubacher, M. G., Cox, D. W. <strong>A null deficiency allele of alpha-1-antitrypsin, Q0-Ludwigshafen, with altered tertiary structure.</strong> J. Clin. Invest. 86: 1878-1884, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2254451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2254451</a>] [<a href="https://doi.org/10.1172/JCI114919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2254451">Fraizer et al., 1990</a>). <a href="#57" class="mim-tip-reference" title="Fraizer, G. C., Siewertsen, M. A., Hofker, M. H., Brubacher, M. G., Cox, D. W. <strong>A null deficiency allele of alpha-1-antitrypsin, Q0-Ludwigshafen, with altered tertiary structure.</strong> J. Clin. Invest. 86: 1878-1884, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2254451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2254451</a>] [<a href="https://doi.org/10.1172/JCI114919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2254451">Fraizer et al. (1990)</a> identified a T-to-A substitution in a German patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2185272+2254451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0032" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 PI Z(WREXHAM)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, SER-19LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs140814100 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs140814100;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs140814100?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs140814100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs140814100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019570 OR RCV000148880 OR RCV000596635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019570, RCV000148880, RCV000596635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019570...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a compound heterozygote with the common disease-producing PI Z mutation (<a href="#0011">107400.0011</a>), <a href="#65" class="mim-tip-reference" title="Graham, A., Hayes, K., Weidinger, S., Newton, C. R., Markham, A. F., Kalsheker, N. A. <strong>Characterisation of the alpha-1-antitrypsin M3 gene, a normal variant.</strong> Hum. Genet. 85: 381-382, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2394452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2394452</a>] [<a href="https://doi.org/10.1007/BF00206766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2394452">Graham et al. (1990)</a> found a change from TCG to TTG in codon -19, which resulted in a change from serine to leucine in the signal peptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2394452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<a id="0033" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 MOVED TO <a href="/entry/107400#0028">107400.0028</a></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0034" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 PI NULL(HONG KONG 2)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(HONG KONG 2)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1,
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019573" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019573" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019573</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0024">107400.0024</a> and <a href="#57" class="mim-tip-reference" title="Fraizer, G. C., Siewertsen, M. A., Hofker, M. H., Brubacher, M. G., Cox, D. W. <strong>A null deficiency allele of alpha-1-antitrypsin, Q0-Ludwigshafen, with altered tertiary structure.</strong> J. Clin. Invest. 86: 1878-1884, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2254451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2254451</a>] [<a href="https://doi.org/10.1172/JCI114919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2254451">Fraizer et al. (1990)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2254451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0035" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 PI NULL(RIEDENBURG)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019603" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019603" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019603</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#116" class="mim-tip-reference" title="Poller, W., Faber, J.-P., Weidinger, S., Olek, K. <strong>DNA polymorphisms associated with a new alpha-1-antitrypsin PI Q0 variant (PI Q0-Riedenburg).</strong> Hum. Genet. 86: 522-524, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673114</a>] [<a href="https://doi.org/10.1007/BF00194647" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1673114">Poller et al. (1991)</a> found complete deletion of the AAT gene as the basis for PI Q0(Riedenburg). The deletion extended into the 3-prime flanking region of the gene but did not include the noncoding AAT-related gene (PIL), which is located 12 kb downstream of AAT (<a href="#72" class="mim-tip-reference" title="Hofker, M. H., Nelen, M., Klasen, E. C., Nukiwa, T., Curiel, D., Crystal, R. G., Frants, R. R. <strong>Cloning and characterization of an alpha-1-antitrypsin like gene 12 kb downstream of the genuine alpha-1-antitrypsin gene.</strong> Biochem. Biophys. Res. Commun. 155: 634-642, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901833</a>] [<a href="https://doi.org/10.1016/s0006-291x(88)80542-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2901833">Hofker et al., 1988</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1673114+2901833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0036" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 PI KALSHEKER-POLLER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, G-A, 3-PRIME UTR ENHANCER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs11568814 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11568814;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs11568814?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs11568814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs11568814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019604 OR RCV000333809 OR RCV004705301" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019604, RCV000333809, RCV004705301" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019604...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#81" class="mim-tip-reference" title="Kalsheker, N. A., Hodgson, I. J., Watkins, G. L., White, J. P., Morrison, H. M., Stockley, R. A. <strong>Deoxyribonucleic acid (DNA) polymorphism of the alpha-1-antitrypsin gene in chronic lung disease.</strong> Brit. Med. J. 294: 1511-1514, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3038256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3038256</a>] [<a href="https://doi.org/10.1136/bmj.294.6586.1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3038256">Kalsheker et al. (1987)</a> and <a href="#117" class="mim-tip-reference" title="Poller, W., Meisen, C., Olek, K. <strong>DNA polymorphisms of the alpha-1-antitrypsin gene region in patients with chronic obstructive pulmonary disease.</strong> Europ. J. Clin. Invest. 20: 1-7, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969347</a>] [<a href="https://doi.org/10.1111/j.1365-2362.1990.tb01769.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1969347">Poller et al. (1990)</a> reported a mutation in the 3-prime flanking sequence of the AAT gene that occurs in about 17% of patients with chronic respiratory disease. The mutation is a G-to-A nucleotide substitution in an octamer (OCT)-like sequence. Because TCGA is converted to TCAA, the mutation is detected as a restriction fragment length polymorphism with the restriction enzyme TaqI. The mutation does not appear to affect basal expression of the protein as the plasma concentration of alpha-1-antitrypsin is normal in persons who carry the mutation; however, binding and functional studies by <a href="#103" class="mim-tip-reference" title="Morgan, K., Scobie, G., Kalsheker, N. A. <strong>Point mutation in a 3-prime flanking sequence of the alpha-1-antitrypsin gene associated with chronic respiratory disease occurs in a regulatory sequence.</strong> Hum. Molec. Genet. 2: 253-257, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499914</a>] [<a href="https://doi.org/10.1093/hmg/2.3.253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499914">Morgan et al. (1993)</a> suggested that it may reduce the rise in plasma AAT concentration that occurs during inflammation. Stimulation by cytokines, such as interleukin-6 (IL6; <a href="/entry/147620">147620</a>), may be lacking. <a href="#103" class="mim-tip-reference" title="Morgan, K., Scobie, G., Kalsheker, N. A. <strong>Point mutation in a 3-prime flanking sequence of the alpha-1-antitrypsin gene associated with chronic respiratory disease occurs in a regulatory sequence.</strong> Hum. Molec. Genet. 2: 253-257, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499914</a>] [<a href="https://doi.org/10.1093/hmg/2.3.253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499914">Morgan et al. (1993)</a> pointed out a precedent for such a mechanism in an unrelated gene: an enhancer element in the 3-prime flanking sequence of the erythropoietin gene increases gene expression nearly 15-fold during hypoxia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1969347+3038256+8499914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0037" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 PI P(DUARTE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, ASP256VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019576 OR RCV000019577 OR RCV000019578 OR RCV000019605 OR RCV000148876 OR RCV000398063 OR RCV003415723" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019576, RCV000019577, RCV000019578, RCV000019605, RCV000148876, RCV000398063, RCV003415723" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019576...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#71" class="mim-tip-reference" title="Hildesheim, J., Kinsley, G., Bissell, M., Pierce, J., Brantly, M. <strong>Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha-1-antitrypsin deficiency variant P(Duarte).</strong> Hum. Mutat. 2: 221-228, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364590</a>] [<a href="https://doi.org/10.1002/humu.1380020311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8364590">Hildesheim et al. (1993)</a> demonstrated that the deficiency-producing change in the PI gene in P(Duarte) is the same as that in P(Lowell) (<a href="#0019">107400.0019</a>). The alleles differ with respect to polymorphic nucleotides at other positions in the gene. They referred to this as genetic diversity from a limited repertoire of mutations on different common allelic backgrounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8364590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0038" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 PI NULL(WEST)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(WEST)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, IVS2DS, G-T, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs751235320 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs751235320;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs751235320?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs751235320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs751235320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019606 OR RCV000169461 OR RCV000593270" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019606, RCV000169461, RCV000593270" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019606...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>During routine screening of individuals applying for enrollment in the US AAT Deficiency Registry, <a href="#94" class="mim-tip-reference" title="Laubach, V. E., Ryan, W. J., Brantly, M. <strong>Characterization of a human alpha-1-antitrypsin null allele involving aberrant mRNA splicing.</strong> Hum. Molec. Genet. 2: 1001-1005, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364536</a>] [<a href="https://doi.org/10.1093/hmg/2.7.1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8364536">Laubach et al. (1993)</a> identified a patient with emphysema and a PI type heterozygous for a novel AAT null allele. The novel allele, designated PI*Q0(West), was characterized by a single G-to-T transversion at position 1 of intron 2, a highly conserved nucleotide position. This resulted in an in-frame deletion of amino acids gly164-to-lys191. This was the first splicing mutation observed in the AAT gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8364536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0039" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 PI S(IIYAMA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, SER53PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs55819880 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs55819880;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs55819880?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs55819880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs55819880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019608 OR RCV000169508" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019608, RCV000169508" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019608...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 32-year-old Japanese male with pulmonary emphysema, <a href="#144" class="mim-tip-reference" title="Yuasa, I., Sugimoto, Y., Ichinose, M., Matsumoto, Y., Fukumaki, Y., Sasaki, T., Okada, K. <strong>PI*S(Iiyama), a deficiency gene of alpha-1-antitrypsin: evidence for the occurrence in western Japan.</strong> Jpn. J. Hum. Genet. 38: 185-191, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8358043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8358043</a>] [<a href="https://doi.org/10.1007/BF01883709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8358043">Yuasa et al. (1993)</a> demonstrated homozygosity for a C-to-T transition at codon 53 resulting in substitution of phenylalanine for serine. They commented on the fact that, in Japanese, deficiency in null alleles at the AAT locus are extremely rare and PI*Z, which occurs at polymorphic frequencies in Caucasians, has not been reported. The only other Japanese case of AAT deficiency was that due to PI M(Nichinan) (<a href="#0017">107400.0017</a>) reported by <a href="#102" class="mim-tip-reference" title="Matsunaga, E., Shiokawa, S., Nakamura, H., Maruyama, T., Tsuda, K., Fukumaki, Y. <strong>Molecular analysis of the gene of the alpha-1-antitrypsin deficiency variant, M(Nichinan).</strong> Am. J. Hum. Genet. 46: 602-612, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309708</a>]" pmid="2309708">Matsunaga et al. (1990)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2309708+8358043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0040" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 PI Z(BRISTOL)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SERPINA1, THR85MET ON M1V
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs199422213 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199422213;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs199422213?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199422213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199422213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019609 OR RCV000512618 OR RCV000731628" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019609, RCV000512618, RCV000731628" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019609...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with an obstetric history of 3 perinatal deaths from fulminant liver disease and no living offspring, <a href="#100" class="mim-tip-reference" title="Lovegrove, J. U., Jeremiah, S., Gillett, G. T., Temple, I. K., Povey, S., Whitehouse, D. B. <strong>A new alpha 1-antitrypsin mutation, thr-met 85, (PI Z-Bristol) associated with novel electrophoresis properties.</strong> Ann. Hum. Genet. 61: 385-391, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9459000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9459000</a>] [<a href="https://doi.org/10.1046/j.1469-1809.1997.6150385.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9459000">Lovegrove et al. (1997)</a> found that she and her father were both heterozygotes for PI M1Z(Bristol). The Z(Bristol) protein was found to be active as a proteinase inhibitor but appeared to be deficient in the plasma to about the same degree as the S protein in MS heterozygotes. It focused on the basic side of Z and lacked the normal pattern of secondary isoforms associated with the commonly occurring AAT variants and migrated faster than normal on an SDS electrophoresis gel. The Z(Bristol) mutation was found to be a C-to-T transition at codon 85, changing ACG (thr) to ATG (met). This disrupted the N-glycosylation site starting at asn83, preventing glycosylation at residue 83 in the PI Z(Bristol) protein, and explained the protein isoelectric focusing and SDS gel electrophoresis results. An analysis of haplotypes in the propositus and her father indicated that the Z(Bristol) mutation occurred on the common M1(val213) genetic background. Of the 3 offspring with perinatal death from fulminant liver disease, 2 were by the woman's husband and 1 by an artificial insemination donor. Of the 2 offspring who were tested for the mutation, 1 had the variant and the other did not. Thus, the relationship between Z(Bristol) and fulminant liver disease in the offspring was unclear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9459000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="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="#Arnaud1978" class="mim-tip-reference" title="Arnaud, P., Galbraith, R. M., Galbraith, G. M. P., Allen, R. C., Fudenberg, H. H. <strong>A new allele of human alpha-1-antitrypsin: Pi (N Hampton).</strong> Am. J. Hum. Genet. 30: 653-659, 1978.">Arnaud et al. (1978)</a>; <a href="#Carrell1982" class="mim-tip-reference" title="Carrell, R. W., Jeppsson, J.-O., Laurell, C.-B., Brennan, S. O., Owen, M. C., Vaughan, L., Boswell, D. R. <strong>Structure and variation of human alpha-1-antitrypsin.</strong> Nature 298: 329-334, 1982.">Carrell et al. (1982)</a>; <a href="#Chapuis-Cellier1981" class="mim-tip-reference" title="Chapuis-Cellier, C., Verdier, M., Lepetit, J. C., Fudenberg, H. H., Arnaud, P. <strong>Pi-Gm linkage: evidence for linkage in males but not in females and for an effect of the S allele of the Pi system.</strong> J. Immunogenet. 8: 257-262, 1981.">Chapuis-Cellier et al.
|
|
(1981)</a>; <a href="#Cox1983" class="mim-tip-reference" title="Cox, D. W., Smyth, S. <strong>Risk for liver disease in adults with alpha-1-antitrypsin deficiency.</strong> Am. J. Med. 74: 221-227, 1983.">Cox and Smyth (1983)</a>; <a href="#Cox1975" class="mim-tip-reference" title="Cox, D. W. <strong>The effect of neuraminidase on genetic variants of alpha-1-antitrypsin.</strong> Am. J. Hum. Genet. 27: 165-177, 1975.">Cox (1975)</a>; <a href="#Cox1980" class="mim-tip-reference" title="Cox, D. W. <strong>Transmission of Z allele from heterozygotes for alpha-1-antitrypsin deficiency. (Letter)</strong> Am. J. Hum. Genet. 32: 455-457, 1980.">Cox (1980)</a>; <a href="#Cox1981" class="mim-tip-reference" title="Cox, D. W. <strong>New variants of alpha-1-antitrypsin: comparison of Pi typing techniques.</strong> Am. J. Hum. Genet. 33: 354-365, 1981.">Cox (1981)</a>; <a href="#Faber1994" class="mim-tip-reference" title="Faber, J. P., Poller, W., Weidinger, S., Kirchgesser, M., Schwaab, R., Bidlingmaier, S., Olek, K. <strong>Identification and DNA sequence analysis of 15 new alpha-1-antitrypsin variants, including two Pi* Q alleles and one deficient Pi* M allele.</strong> Am. J. Hum. Genet. 55: 1113-1121, 1994.">Faber et al. (1994)</a>; <a href="#Faber1989" class="mim-tip-reference" title="Faber, J. P., Weidinger, S., Olek, K. <strong>Sequence data of two rare deficient alpha-1-antitrypsin phenotypes. (Abstract)</strong> Cytogenet. Cell Genet. 51: 995-996, 1989.">Faber et al. (1989)</a>; <a href="#Fagerhol1981" class="mim-tip-reference" title="Fagerhol, M. K., Cox, D. W. <strong>The Pi polymorphism: genetic, biochemical, and clinical aspects of human alpha-1-antitrypsin.</strong> Adv. Hum. Genet. 11: 1-62, 1981.">Fagerhol and Cox (1981)</a>; <a href="#Fagerhol1969" class="mim-tip-reference" title="Fagerhol, M. K., Gedde-Dahl, T., Jr. <strong>Genetics of the Pi serum types: family studies of the inherited variants of serum alpha-1-antitrypsin.</strong> Hum. Hered. 19: 354-359, 1969.">Fagerhol and Gedde-Dahl (1969)</a>; <a href="#Fagerhol1968" class="mim-tip-reference" title="Fagerhol, M. K. <strong>The Pi system: genetic variants of serum alpha-1-antitrypsin.</strong> Ser. Haemat. 1: 153-161, 1968.">Fagerhol and Hauge (1968)</a>; <a href="#Fagerhol1970" class="mim-tip-reference" title="Fagerhol, M. K., Laurell, C. B. <strong>The Pi system--inherited variants of serum alpha-1-antitrypsin.</strong> Prog. Med. Genet. 7: 96-111, 1970.">Fagerhol
|
|
and Laurell (1970)</a>; <a href="#Fagerhol1968" class="mim-tip-reference" title="Fagerhol, M. K. <strong>The Pi system: genetic variants of serum alpha-1-antitrypsin.</strong> Ser. Haemat. 1: 153-161, 1968.">Fagerhol and Tenfjord (1968)</a>; <a href="#Frants1980" class="mim-tip-reference" title="Frants, R., Eriksson, A. W. <strong>A new unstable Pi M variant of alpha-1-antitrypsin in a Finnish isolate.</strong> Hum. Hered. 30: 333-342, 1980.">Frants and Eriksson
|
|
(1980)</a>; <a href="#Gedde-Dahl1975" class="mim-tip-reference" title="Gedde-Dahl, T., Jr., Cook, P. J. L., Fagerhol, M. K., Pierce, J. A. <strong>The Gm-Pi linkage: a summary estimate.</strong> Birth Defects Orig. Art. Ser. XI(3): 157-158, 1975. Note: Alternate: Cytogenet. Cell Genet. 14: 327-328, 1975.">Gedde-Dahl et al. (1975)</a>; <a href="#Graham1990" class="mim-tip-reference" title="Graham, A., Kalsheker, N. A., Bamforth, F. J., Newton, C. R., Markham, A. F. <strong>Molecular characterization of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) null(Newport) (gly(115)-to-ser) and (Pi) Z Wrexham (ser(-19)-to-leu).</strong> Hum. Genet. 85: 537-540, 1990.">Graham et al. (1990)</a>; <a href="#Holmes1990" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Fells, G. A., Crystal, R. G. <strong>Alpha-1-antitrypsin W(Bethesda): molecular basis of an unusual alpha-1-antitrypsin deficiency variant.</strong> Biochem. Biophys. Res. Commun. 170: 1013-1020, 1990.">Holmes et al.
|
|
(1990)</a>; <a href="#Holmes1990" class="mim-tip-reference" title="Holmes, M. D., Brantly, M. L., Fells, G. A., Crystal, R. G. <strong>Alpha-1-antitrypsin W(Bethesda): molecular basis of an unusual alpha-1-antitrypsin deficiency variant.</strong> Biochem. Biophys. Res. Commun. 170: 1013-1020, 1990.">Holmes et al. (1990)</a>; <a href="#Hug1980" class="mim-tip-reference" title="Hug, G., Chuck, G., Slemmer, T. M., Fagerhol, M. K. <strong>Pi (Ecincinnati): a new alpha-1-antitrypsin allele in three Negro families.</strong> Hum. Genet. 54: 361-364, 1980.">Hug et al. (1980)</a>; <a href="#Iammarino1979" class="mim-tip-reference" title="Iammarino, R. M., Wagener, D. K., Allen, R. C. <strong>Segregation distortion of the alpha-1-antitrypsin Pi Z allele.</strong> Am. J. Hum. Genet. 31: 508-517, 1979.">Iammarino et al.
|
|
(1979)</a>; <a href="#Kramps1981" class="mim-tip-reference" title="Kramps, J. A., Brouwers, J. W., Maesen, F., Dijkman, J. H. <strong>Pi(M-Heerlen), a Pi(M) allele resulting in very low alpha-1-antitrypsin serum levels.</strong> Hum. Genet. 59: 104-107, 1981.">Kramps et al. (1981)</a>; <a href="#Kueppers1978" class="mim-tip-reference" title="Kueppers, F., Christopherson, M. J. <strong>Alpha-1-antitrypsin: further genetic heterogeneity revealed by isoelectric focusing.</strong> Am. J. Hum. Genet. 30: 359-365, 1978.">Kueppers and Christopherson (1978)</a>; <a href="#Lopez1964" class="mim-tip-reference" title="Lopez, V., Oetliker, O., Colombo, J. P., Butler, R. <strong>Ein Fall von familiaerem alpha-1-Antitrypsinmangel.</strong> Helv. Paediat. Acta 19: 296-303, 1964.">Lopez et al. (1964)</a>; <a href="#Nukiwa1986" class="mim-tip-reference" title="Nukiwa, T., Brantly, M., Garver, R., Paul, L., Courtney, M., LeCocq, J.-P., Crystal, R. G. <strong>Evaluation of 'at risk' alpha-1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes.</strong> J. Clin. Invest. 77: 528-537, 1986.">Nukiwa et al. (1986)</a>; <a href="#Owen1976" class="mim-tip-reference" title="Owen, M. C., Carrell, R. W. <strong>Alpha-1-antitrypsin: molecular abnormality of S variant.</strong> Brit. Med. J. 1: 130-131, 1976.">Owen et al. (1976)</a>; <a href="#Weitkamp1978" class="mim-tip-reference" title="Weitkamp, L. R., Cox, D., Guttormsen, S., Johnston, E., Hempfling, S. <strong>Allelic specific heterogeneity in the Pi-Gm linkage group.</strong> Cytogenet. Cell Genet. 22: 647-650, 1978.">Weitkamp et al. (1978)</a>; <a href="#Welch1980" class="mim-tip-reference" title="Welch, S. G., McGregor, I. A., Williams, K. <strong>Alpha-1-antitrypsin (Pi) phenotypes in a village population from the Gambia, West Africa.</strong> Hum. Genet. 53: 233-235, 1980.">Welch et al. (1980)</a>; <a href="#Yoshida1976" class="mim-tip-reference" title="Yoshida, A., Lieberman, J., Gaidulis, L., Ewing, C. <strong>Molecular abnormality of human alpha-1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency.</strong> Proc. Nat. Acad. Sci. 73: 1324-1328, 1976.">Yoshida et al. (1976)</a>; <a href="#Yoshida1979" class="mim-tip-reference" title="Yoshida, A., Taylor, J. C., Van den Brock, W. G. M. <strong>Structural difference between the normal PiM(1) and the common PiM(2) variant of human alpha-1-antitrypsin.</strong> Am. J. Hum. Genet. 31: 564-568, 1979.">Yoshida et al. (1979)</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="Arnaud1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Arnaud, P., Galbraith, R. M., Galbraith, G. M. P., Allen, R. C., Fudenberg, H. H.
|
|
<strong>A new allele of human alpha-1-antitrypsin: Pi (N Hampton).</strong>
|
|
Am. J. Hum. Genet. 30: 653-659, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/311584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">311584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=311584" 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="2" class="mim-anchor"></a>
|
|
<a id="Axelsson1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Axelsson, U., Laurell, C. B.
|
|
<strong>Hereditary variants of serum alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 17: 466-472, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4158556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4158556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4158556" 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="3" class="mim-anchor"></a>
|
|
<a id="Babron1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Babron, M. C., Constans, J., Dugoujon, J. M., Cambon-Thomsen, A., Bonaiti-Pellie, C.
|
|
<strong>The Gm-Pi linkage in 843 French families: effect of the alleles Pi Z and Pi S.</strong>
|
|
Ann. Hum. Genet. 54: 107-113, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2382967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2382967</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2382967" 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.1469-1809.1990.tb00366.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bartlett2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bartlett, J. R., Friedman, K. J., Ling, S. C., Pace, R. G., Bell, S. C., Bourke, B., Castaldo, G., Castellani, C., Cipolli, M., Colombo, C., Colombo, J. L., Debray, D., and 22 others.
|
|
<strong>Genetic modifiers of liver disease in cystic fibrosis.</strong>
|
|
JAMA 302: 1076-1083, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19738092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19738092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19738092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jama.2009.1295" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bender1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bender, K., Muller, C. R., Schmidt, A., Strohmaier, U., Wienker, T. F.
|
|
<strong>Linkage studies on the human Pi, Gm, GLO, and HLA genes.</strong>
|
|
Hum. Genet. 49: 159-166, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/112033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">112033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=112033" 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/BF00277637" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Billingsley1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Billingsley, G. D., Walter, M. A., Cox, D. W.
|
|
<strong>Physical linkage of alpha-1-antitrypsin and alpha-1-antichymotrypsin by pulsed field gel electrophoresis. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45 (suppl.): A130, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Billingsley1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Billingsley, G. D., Walter, M. A., Hammond, G. L., Cox, D. W.
|
|
<strong>Physical mapping of four serpin genes: alpha-1-antitrypsin, alpha-1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome 14q32.1.</strong>
|
|
Am. J. Hum. Genet. 52: 343-353, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8381582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8381582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8381582" 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="8" class="mim-anchor"></a>
|
|
<a id="Blanco2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blanco, I., Bustillo, E. F., Rodriguez, M. C.
|
|
<strong>Distribution of alpha-1-antitrypsin PI S and PI Z frequencies in countries outside Europe: a meta-analysis.</strong>
|
|
Clin. Genet. 60: 431-441, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11846735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11846735</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11846735" 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.1399-0004.2001.600605.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Boomsma1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boomsma, D. I., Frants, R. R., Bank, R. A., Martin, N. G.
|
|
<strong>Protease inhibitor (Pi) locus, fertility and twinning.</strong>
|
|
Hum. Genet. 89: 329-332, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1601424" 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/BF00220552" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Botstein1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Botstein, D., White, R. L., Skolnick, M., Davis, R. W.
|
|
<strong>Construction of a genetic linkage map in man using restriction fragment length polymorphisms.</strong>
|
|
Am. J. Hum. Genet. 32: 314-331, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6247908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6247908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6247908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Brantly1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brantly, M., Courtney, M., Crystal, R. G.
|
|
<strong>Repair of the secretion defect in the Z form of alpha-1-antitrypsin by addition of a second mutation.</strong>
|
|
Science 242: 1700-1702, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2904702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2904702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2904702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.2904702" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Brennan1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brennan, S. O., Carrell, R. W.
|
|
<strong>Alpha-1-antitrypsin Christchurch, 363 glu-to-lys: mutation at the P-prime-5 position does not affect inhibitory activity.</strong>
|
|
Biochim. Biophys. Acta 873: 13-19, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3527273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3527273</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3527273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0167-4838(86)90183-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Bristow2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bristow, C. L., Mercatante, D. R., Kole, R.
|
|
<strong>HIV-1 preferentially binds receptors copatched with cell-surface elastase.</strong>
|
|
Blood 102: 4479-4486, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12933574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12933574</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12933574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2003-05-1635" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Bristow2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bristow, C. L., Patel, H., Arnold, R. R.
|
|
<strong>Self antigen prognostic for human immunodeficiency virus disease progression.</strong>
|
|
Clin. Diagn. Lab. Immun. 8: 937-942, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11527807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11527807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11527807[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11527807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/CDLI.8.5.937-942.2001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Bristow2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bristow, C. L.
|
|
<strong>Slow human immunodeficiency virus (HIV) infectivity correlated with low HIV coreceptor levels.</strong>
|
|
Clin. Diagn. Lab. Immun. 8: 932-936, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11527806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11527806</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11527806[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11527806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/CDLI.8.5.932-936.2001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Campbell2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Campbell, R. A., Campbell, H. D., Bircher, J. S., de Araujo, C. V., Denorme, F., Crandell, J. L., Rustad, J. L., Monts, J., Cody, M. J., Kosaka, Y., Yost, C. C.
|
|
<strong>Placental HTRA1 cleaves alpha-1-antitrypsin to generate a NET-inhibitory peptide.</strong>
|
|
Blood 138: 977-988, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34192300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34192300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34192300[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34192300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood.2020009021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Carrell1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carrell, R. W., Jeppsson, J.-O., Laurell, C.-B., Brennan, S. O., Owen, M. C., Vaughan, L., Boswell, D. R.
|
|
<strong>Structure and variation of human alpha-1-antitrypsin.</strong>
|
|
Nature 298: 329-334, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7045697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7045697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7045697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/298329a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Carrell1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carrell, R. W.
|
|
<strong>Alpha-1-antitrypsin: molecular pathology, leukocytes, and tissue damage.</strong>
|
|
J. Clin. Invest. 78: 1427-1431, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3537008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3537008</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3537008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112731" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Chappell2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chappell, S., Daly, L., Morgan, K., Baranes, T. G., Roca, J., Rabinovich, R., Millar, A., Donnelly, S. C., Keatings, V., MacNee, W., Stolk, J., Hiemstra, P., Miniati, M., Monti, S., O'Connor, C. M., Kalsheker, N.
|
|
<strong>Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease.</strong>
|
|
Hum. Mutat. 27: 103-109, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20275" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Chapuis-Cellier1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chapuis-Cellier, C., Verdier, M., Lepetit, J. C., Fudenberg, H. H., Arnaud, P.
|
|
<strong>Pi-Gm linkage: evidence for linkage in males but not in females and for an effect of the S allele of the Pi system.</strong>
|
|
J. Immunogenet. 8: 257-262, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6792288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6792288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6792288" 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.1744-313x.1981.tb00767.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Clark1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clark, P., Breit, S. N., Dawkins, R. L., Penny, R.
|
|
<strong>Genetic study of a family with two members with Weber-Christian disease (panniculitis) and alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Med. Genet. 13: 57-62, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982619</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320130110" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Clark1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clark, P., Martin, N. G.
|
|
<strong>An excess of the Pi(s) allele in dizygotic twins and their mothers.</strong>
|
|
Hum. Genet. 61: 171-174, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982218" 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/BF00274213" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Cox1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Billingsley, G. D., Mansfield, T.
|
|
<strong>DNA restriction-site polymorphisms associated with the alpha-1-antitrypsin gene.</strong>
|
|
Am. J. Hum. Genet. 41: 891-906, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2890296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2890296</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2890296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Cox1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Levison, H.
|
|
<strong>Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes).</strong>
|
|
Am. Rev. Respir. Dis. 137: 371-375, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3257661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3257661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3257661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1164/ajrccm/137.2.371" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Cox1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Markovic, V. D., Teshima, I. E.
|
|
<strong>Genes for immunoglobulin heavy chains and for alpha-1-antitrypsin are localized to specific regions of chromosome 14q.</strong>
|
|
Nature 297: 428-430, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6804874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6804874</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6804874" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/297428a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Cox1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Smyth, S.
|
|
<strong>Risk for liver disease in adults with alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Med. 74: 221-227, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6600583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6600583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6600583" 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(83)90615-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Cox1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Woo, S. L. C., Mansfield, T.
|
|
<strong>DNA restriction fragments associated with alpha-1-antitrypsin indicate a single origin for deficiency allele PI Z.</strong>
|
|
Nature 316: 79-81, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2989709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2989709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2989709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/316079a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Cox1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>The effect of neuraminidase on genetic variants of alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 27: 165-177, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1079112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1079112</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1079112" 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="29" class="mim-anchor"></a>
|
|
<a id="Cox1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Genetic variation in alpha-1-antitrypsin. (Editorial)</strong>
|
|
Am. J. Hum. Genet. 30: 660-662, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/311585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">311585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=311585" 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="30" class="mim-anchor"></a>
|
|
<a id="Cox1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Transmission of Z allele from heterozygotes for alpha-1-antitrypsin deficiency. (Letter)</strong>
|
|
Am. J. Hum. Genet. 32: 455-457, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17948551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17948551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17948551" 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="Cox1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>New variants of alpha-1-antitrypsin: comparison of Pi typing techniques.</strong>
|
|
Am. J. Hum. Genet. 33: 354-365, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6972696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6972696</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6972696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Cox1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Alpha-1-antitrypsin deficiency. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic Basis of Inherited Disease. (6th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Cox2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Alpha-1-antitrypsin. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. IV. (8th ed.)</strong>
|
|
New York: McGraw-Hill 2001. Pp. 5559-5584.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Crystal1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crystal, R. G.
|
|
<strong>The alpha-1-antitrypsin gene and its deficiency states.</strong>
|
|
Trends Genet. 5: 411-417, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2696185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2696185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2696185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0168-9525(89)90200-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Crystal1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy.</strong>
|
|
J. Clin. Invest. 85: 1343-1352, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2185272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2185272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2185272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI114578" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Curiel1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Curiel, D., Brantly, M., Curiel, E., Stier, L., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin deficiency caused by the alpha-1-antitrypsin null(Mattawa) gene: an insertion mutation rendering the alpha-1-antitrypsin gene incapable of producing alpha-1-antitrypsin.</strong>
|
|
J. Clin. Invest. 83: 1144-1152, 1989. Note: Erratum: J. Clin. Invest. 84: following 1041, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2539391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2539391</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2539391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI113994" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Curiel1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Curiel, D. T., Chytil, A., Courtney, M., Crystal, R. G.
|
|
<strong>Serum alpha-1-antitrypsin deficiency associated with the common S-type (glu264-to-val) mutation results from intracellular degradation of alpha-1-antitrypsin prior to secretion.</strong>
|
|
J. Biol. Chem. 264: 10477-10486, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2567291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2567291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2567291" 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="38" class="mim-anchor"></a>
|
|
<a id="Curiel1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Curiel, D. T., Holmes, M. D., Okayama, H., Brantly, M. L., Vogelmeier, C., Travis, W. D.
|
|
<strong>Stier, L. E.; Perks, W. H. and Crystal, R. G.: Molecular basis of the liver and lung disease associated with the alpha-1-antitrypsin deficiency allele M(Malton).</strong>
|
|
J. Biol. Chem. 264: 13938-13945, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2788166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2788166</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2788166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Curiel1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Curiel, D. T., Vogelmeier, C., Hubbard, R. C., Stier, L. E., Crystal, R. G.
|
|
<strong>Molecular basis of alpha-1-antitrypsin deficiency and emphysema associated with the alpha-1-antitrypsin M(Mineral Springs) allele.</strong>
|
|
Molec. Cell. Biol. 10: 47-56, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967187</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1967187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/mcb.10.1.47-56.1990" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Darlington1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Darlington, G. J., Astrin, K. H., Muirhead, S. P., Desnick, R. J., Smith, M.
|
|
<strong>Assignment of human alpha-1-antitrypsin to chromosome 14 by somatic cell hybrid analysis.</strong>
|
|
Proc. Nat. Acad. Sci. 79: 870-873, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6801664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6801664</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6801664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.79.3.870" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="DeCroo1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
DeCroo, S., Kamboh, M. I., Ferrell, R. E.
|
|
<strong>Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.</strong>
|
|
Hum. Hered. 41: 215-221, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783408</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1783408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000154004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Dycaico1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dycaico, M. J., Grant, S. G. N., Felts, K., Nichols, W. S., Geller, S. A., Hager, J. H., Pollard, A. J., Kohler, S. W., Short, H. P., Jirik, F. R., Hanahan, D., Sorge, J. A.
|
|
<strong>Neonatal hepatitis induced by alpha-1-antitrypsin: a transgenic mouse model.</strong>
|
|
Science 242: 1409-1415, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3264419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3264419</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3264419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3264419" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Emmerich1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Emmerich, J., Alhenc-Gelas, M., Gandrille, S., Guichet, C., Fiessinger, J.-N., Aiach, M.
|
|
<strong>Mechanism of protein C deficiency in a patient with arginine 358 alpha(1)-antitrypsin (Pittsburgh mutation): role in the maintenance of hemostatic balance.</strong>
|
|
J. Lab. Clin. Med. 125: 531-539, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7706910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7706910</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7706910" 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="44" class="mim-anchor"></a>
|
|
<a id="Faber1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Faber, J. P., Poller, W., Weidinger, S., Kirchgesser, M., Schwaab, R., Bidlingmaier, S., Olek, K.
|
|
<strong>Identification and DNA sequence analysis of 15 new alpha-1-antitrypsin variants, including two Pi* Q alleles and one deficient Pi* M allele.</strong>
|
|
Am. J. Hum. Genet. 55: 1113-1121, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7977369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7977369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7977369" 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="45" class="mim-anchor"></a>
|
|
<a id="Faber1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Faber, J. P., Weidinger, S., Goedde, H.-W., Olek, K.
|
|
<strong>The deficient alpha-1-antitrypsin phenotype Pi P is associated with an A-to-T transversion in exon III of the gene. (Letter)</strong>
|
|
Am. J. Hum. Genet. 45: 161-163, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2787118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2787118</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2787118" 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="46" class="mim-anchor"></a>
|
|
<a id="Faber1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Faber, J. P., Weidinger, S., Olek, K.
|
|
<strong>Sequence data of two rare deficient alpha-1-antitrypsin phenotypes. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 995-996, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Faber1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Faber, J.-P., Weidinger, S., Olek, K.
|
|
<strong>Sequence data of the rare deficient alpha-1-antitrypsin variant PI Z(Augsburg).</strong>
|
|
Am. J. Hum. Genet. 46: 1158-1162, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2339709" 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="48" class="mim-anchor"></a>
|
|
<a id="Fagerhol1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Braend, M.
|
|
<strong>Serum prealbumin: polymorphism in man.</strong>
|
|
Science 149: 986-987, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5827347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5827347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5827347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.149.3687.986" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Fagerhol1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Cox, D. W.
|
|
<strong>The Pi polymorphism: genetic, biochemical, and clinical aspects of human alpha-1-antitrypsin.</strong>
|
|
Adv. Hum. Genet. 11: 1-62, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6168185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6168185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6168185" 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="50" class="mim-anchor"></a>
|
|
<a id="Fagerhol1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Gedde-Dahl, T., Jr.
|
|
<strong>Genetics of the Pi serum types: family studies of the inherited variants of serum alpha-1-antitrypsin.</strong>
|
|
Hum. Hered. 19: 354-359, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5366282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5366282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5366282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000152238" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Fagerhol1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Hauge, H. E.
|
|
<strong>The Pi phenotype MP: discovery of a ninth allele belonging to the system of inherited variants of serum alpha-1-antitrypsin.</strong>
|
|
Vox Sang. 15: 396-400, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5699691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5699691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5699691" 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.1423-0410.1968.tb04081.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Fagerhol1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Laurell, C. B.
|
|
<strong>The polymorphism of 'prealbumins' and alpha-1-antitrypsin in human sera.</strong>
|
|
Clin. Chim. Acta 16: 199-203, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4166396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4166396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4166396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0009-8981(67)90181-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Fagerhol1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Laurell, C. B.
|
|
<strong>The Pi system--inherited variants of serum alpha-1-antitrypsin.</strong>
|
|
Prog. Med. Genet. 7: 96-111, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4911922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4911922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4911922" 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="54" class="mim-anchor"></a>
|
|
<a id="Fagerhol1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Tenfjord, O. W.
|
|
<strong>Serum Pi types in some European, American, Asian and African populations.</strong>
|
|
Acta Path. Microbiol. Scand. 72: 601-608, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5681806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5681806</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5681806" 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.1699-0463.1968.tb00472.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Fagerhol1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K.
|
|
<strong>The Pi system: genetic variants of serum alpha-1-antitrypsin.</strong>
|
|
Ser. Haemat. 1: 153-161, 1968.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Fraizer1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fraizer, G. C., Harrold, T. R., Hofker, M. H., Cox, D. W.
|
|
<strong>In-frame single codon deletion in the M(Malton) deficiency allele of alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 44: 894-902, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786335</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2786335" 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="57" class="mim-anchor"></a>
|
|
<a id="Fraizer1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fraizer, G. C., Siewertsen, M. A., Hofker, M. H., Brubacher, M. G., Cox, D. W.
|
|
<strong>A null deficiency allele of alpha-1-antitrypsin, Q0-Ludwigshafen, with altered tertiary structure.</strong>
|
|
J. Clin. Invest. 86: 1878-1884, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2254451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2254451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2254451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI114919" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Fraizer1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fraizer, G. C., Siewertsen, M., Harold, T. R., Cox, D. W.
|
|
<strong>Deletion/frameshift mutation in the alpha-1-antitrypsin null allele, PI*Q0(Bolton).</strong>
|
|
Hum. Genet. 83: 377-382, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2807278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2807278</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2807278" 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/BF00291385" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Frants1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frants, R., Eriksson, A. W.
|
|
<strong>A new unstable Pi M variant of alpha-1-antitrypsin in a Finnish isolate.</strong>
|
|
Hum. Hered. 30: 333-342, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6971248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6971248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6971248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000153154" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Garver1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garver, R. I., Jr., Mornex, J.-F., Nukiwa, T., Brantly, M., Courtney, M., LeCocq, J.-P., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin deficiency and emphysema caused by homozygous inheritance of non-expressing alpha-1-antitrypsin genes.</strong>
|
|
New Eng. J. Med. 314: 762-766, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485249" 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/NEJM198603203141207" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Gedde-Dahl1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Cook, P. J. L., Fagerhol, M. K., Pierce, J. A.
|
|
<strong>Improved estimate of the Gm-Pi linkage.</strong>
|
|
Ann. Hum. Genet. 39: 43-50, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/810069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">810069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=810069" 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.1469-1809.1975.tb00106.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Gedde-Dahl1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Cook, P. J. L., Fagerhol, M. K., Pierce, J. A.
|
|
<strong>The Gm-Pi linkage: a summary estimate.</strong>
|
|
Birth Defects Orig. Art. Ser. XI(3): 157-158, 1975. Note: Alternate: Cytogenet. Cell Genet. 14: 327-328, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/54196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">54196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=54196" 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="63" class="mim-anchor"></a>
|
|
<a id="Gedde-Dahl1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Fagerhol, M. K., Cook, P. J. L., Noades, J.
|
|
<strong>Autosomal linkage between the Gm and Pi loci in man.</strong>
|
|
Ann. Hum. Genet. 35: 393-400, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5073686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5073686</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5073686" 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="64" class="mim-anchor"></a>
|
|
<a id="Gedde-Dahl1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Frants, R., Olaisen, B., Eriksson, A. W., van Loghem, E., Lamm, L.
|
|
<strong>The Gm-Pi linkage heterogeneity in view of Pi M subtypes.</strong>
|
|
Ann. Hum. Genet. 45: 143-153, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6797346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6797346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6797346" 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.1469-1809.1981.tb00316.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Graham1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Graham, A., Hayes, K., Weidinger, S., Newton, C. R., Markham, A. F., Kalsheker, N. A.
|
|
<strong>Characterisation of the alpha-1-antitrypsin M3 gene, a normal variant.</strong>
|
|
Hum. Genet. 85: 381-382, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2394452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2394452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2394452" 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/BF00206766" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Graham1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Graham, A., Kalsheker, N. A., Bamforth, F. J., Newton, C. R., Markham, A. F.
|
|
<strong>Molecular characterization of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) null(Newport) (gly(115)-to-ser) and (Pi) Z Wrexham (ser(-19)-to-leu).</strong>
|
|
Hum. Genet. 85: 537-540, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2227940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2227940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2227940" 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/BF00194233" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Graham1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Graham, A., Kalsheker, N. A., Newton, C. R., Bamforth, F. J., Powell, S. J., Markham, A. F.
|
|
<strong>Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null (Cardiff) (asp256-to-val), Pi M(Malton) (phe51-deletion) and Pi I (arg39-to-cys).</strong>
|
|
Hum. Genet. 84: 55-58, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2606478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2606478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2606478" 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/BF00210671" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Green2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, C., Brown, G., Dafforn, T. R., Reichhart, J.-M., Morley, T., Lomas, D. A., Gubb, D.
|
|
<strong>Drosophila necrotic mutations mirror disease-associated variants of human serpins.</strong>
|
|
Development 130: 1473-1478, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1242/dev.00350" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Hafeez1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hafeez, W., Ciliberto, G., Perlmutter, D. H.
|
|
<strong>Constitutive and modulated expression of the human alpha-1 antitrypsin gene: different transcriptional initiation sites used in three different cell types.</strong>
|
|
J. Clin. Invest. 89: 1214-1222, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1556183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1556183</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1556183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115705" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Hidvegi2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hidvegi, T., Ewing, M., Hale, P., Dippold, C., Beckett, C., Kemp, C., Maurice, N., Mukherjee, A., Goldbach, C., Watkins, S., Michalopoulos, G., Perlmutter, D. H.
|
|
<strong>An autophagy-enhancing drug promotes degradation of mutant alpha-1-antitrypsin Z and reduces hepatic fibrosis.</strong>
|
|
Science 329: 229-232, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20522742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20522742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20522742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1190354" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Hildesheim1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hildesheim, J., Kinsley, G., Bissell, M., Pierce, J., Brantly, M.
|
|
<strong>Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha-1-antitrypsin deficiency variant P(Duarte).</strong>
|
|
Hum. Mutat. 2: 221-228, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364590</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8364590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380020311" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Hofker1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hofker, M. H., Nelen, M., Klasen, E. C., Nukiwa, T., Curiel, D., Crystal, R. G., Frants, R. R.
|
|
<strong>Cloning and characterization of an alpha-1-antitrypsin like gene 12 kb downstream of the genuine alpha-1-antitrypsin gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 155: 634-642, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2901833" 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/s0006-291x(88)80542-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Hofker1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hofker, M. H., Nukiwa, T., van Paassen, H. M. B., Nelen, M., Kramps, J. A., Klasen, E. C., Frants, R. R., Crystal, R. G.
|
|
<strong>A pro-to-leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen.</strong>
|
|
Hum. Genet. 81: 264-268, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2784123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2784123</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2784123" 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/BF00279001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Holmes1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmes, M. D., Brantly, M. L., Crystal, R. G.
|
|
<strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong>
|
|
Am. Rev. Resp. Dis. 142: 1185-1192, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2240842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2240842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2240842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1164/ajrccm/142.5.1185" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Holmes1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmes, M. D., Brantly, M. L., Curiel, D. T., Weidinger, S., Crystal, R. G.
|
|
<strong>Characterization of the normal alpha-1-antitrypsin allele V(Munich): a variant associated with a unique protein isoelectric focusing pattern.</strong>
|
|
Am. J. Hum. Genet. 46: 810-816, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2316526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2316526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2316526" 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="76" class="mim-anchor"></a>
|
|
<a id="Holmes1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmes, M. D., Brantly, M. L., Fells, G. A., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin W(Bethesda): molecular basis of an unusual alpha-1-antitrypsin deficiency variant.</strong>
|
|
Biochem. Biophys. Res. Commun. 170: 1013-1020, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2390072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2390072</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2390072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(90)90493-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Hug1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hug, G., Chuck, G., Fagerhol, M. K.
|
|
<strong>Pi(P-Clifton): a new alpha(1) antitrypsin allele in an American Negro family.</strong>
|
|
J. Med. Genet. 18: 43-45, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6973024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6973024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6973024" 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.18.1.43" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Hug1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hug, G., Chuck, G., Slemmer, T. M., Fagerhol, M. K.
|
|
<strong>Pi (Ecincinnati): a new alpha-1-antitrypsin allele in three Negro families.</strong>
|
|
Hum. Genet. 54: 361-364, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6967446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6967446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6967446" 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/BF00291583" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Hutchison1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hutchison, D. C. S.
|
|
<strong>Alpha-1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z.</strong>
|
|
Respir. Med. 92: 367-377, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9692092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9692092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9692092" 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/s0954-6111(98)90278-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Iammarino1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iammarino, R. M., Wagener, D. K., Allen, R. C.
|
|
<strong>Segregation distortion of the alpha-1-antitrypsin Pi Z allele.</strong>
|
|
Am. J. Hum. Genet. 31: 508-517, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/314754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">314754</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=314754" 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="81" class="mim-anchor"></a>
|
|
<a id="Kalsheker1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kalsheker, N. A., Hodgson, I. J., Watkins, G. L., White, J. P., Morrison, H. M., Stockley, R. A.
|
|
<strong>Deoxyribonucleic acid (DNA) polymorphism of the alpha-1-antitrypsin gene in chronic lung disease.</strong>
|
|
Brit. Med. J. 294: 1511-1514, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3038256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3038256</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3038256" 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.294.6586.1511" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Kalsheker1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kalsheker, N., Hayes, K., Weidinger, S., Graham, A.
|
|
<strong>What is Pi (proteinase inhibitor) null or PiQ0? A problem highlighted by the alpha-1-antitrypsin M(Heerlen) mutation.</strong>
|
|
J. Med. Genet. 29: 27-29, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1552539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1552539</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1552539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.29.1.27" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Kamimoto2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kamimoto, T., Shoji, S., Hidvegi, T., Mizushima, N., Umebayashi, K., Perlmutter, D. H., Yoshimori, T.
|
|
<strong>Intracellular inclusions containing mutant alpha(1)-antitrypsin Z are propagated in the absence of autophagic activity.</strong>
|
|
J. Biol. Chem. 281: 4467-4476, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16365039/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16365039</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16365039" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M509409200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Kawakami1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kawakami, Y., Irie, T., Kishi, F., Asanuma, Y., Shida, A., Yoshikawa, T., Kamishima, K., Hasegawa, H., Murao, M.
|
|
<strong>Familial aggregation of abnormal ventilatory control and pulmonary function in chronic obstructive pulmonary disease.</strong>
|
|
Europ. J. Resp. Dis. 62: 56-64, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7227484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7227484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7227484" 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="85" class="mim-anchor"></a>
|
|
<a id="Kelly2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kelly, E., Greene, C. M., Carroll, T. P., McElvaney, N. G., O'Neill, S. J.
|
|
<strong>Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha-1-antitrypsin deficiency.</strong>
|
|
J. Biol. Chem. 284: 16891-16897, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19398551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19398551</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19398551[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19398551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M109.006288" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Keyeux1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keyeux, G., Gilgenkrantz, S., Lefranc, G., Lefranc, M.-P.
|
|
<strong>Molecular characterization of a ring chromosome 14 showing that the PI locus is centromeric to the D14S1 and IGH loci.</strong>
|
|
Hum. Genet. 82: 219-222, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2543620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2543620</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2543620" 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/BF00291158" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Khodayari2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Khodayari, N., Wang, R. L., Marek, G., Krotova, K., Kirst, M., Liu, C., Rouhani, F., Brantly, M.
|
|
<strong>SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78.</strong>
|
|
PLoS One 12: e0172983, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28301499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28301499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28301499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28301499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1371/journal.pone.0172983" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Kramps1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kramps, J. A., Brouwers, J. W., Maesen, F., Dijkman, J. H.
|
|
<strong>Pi(M-Heerlen), a Pi(M) allele resulting in very low alpha-1-antitrypsin serum levels.</strong>
|
|
Hum. Genet. 59: 104-107, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6976926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6976926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6976926" 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/BF00293055" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Kueppers1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kueppers, F., Bearn, A. G.
|
|
<strong>An inherited alpha-1-antitrypsin variant.</strong>
|
|
Humangenetik 4: 217-220, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6080804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6080804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6080804" 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/BF00292195" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Kueppers1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kueppers, F., Christopherson, M. J.
|
|
<strong>Alpha-1-antitrypsin: further genetic heterogeneity revealed by isoelectric focusing.</strong>
|
|
Am. J. Hum. Genet. 30: 359-365, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/309724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">309724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=309724" 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="91" class="mim-anchor"></a>
|
|
<a id="Kurachi1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kurachi, K., Chandra, T., Degen, S. J. F., White, T. T., Marchioro, T. L., Woo, S. L. C., Davie, E. W.
|
|
<strong>Cloning and sequence of cDNA coding for alpha-1-antitrypsin.</strong>
|
|
Proc. Nat. Acad. Sci. 78: 6826-6830, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7031661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7031661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7031661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.78.11.6826" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Lace2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lace, B., Sveger, T., Krams, A., Cernevska, G., Krumina, A.
|
|
<strong>Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis.</strong>
|
|
Ann. Hum. Genet. 72: 300-304, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18294358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18294358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18294358" 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.1469-1809.2008.00431.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Lai1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lai, E. C., Kao, F.-T., Law, M. L., Woo, S. L. C.
|
|
<strong>Assignment of the alpha-1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization.</strong>
|
|
Am. J. Hum. Genet. 35: 385-392, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6602546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6602546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6602546" 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="94" class="mim-anchor"></a>
|
|
<a id="Laubach1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laubach, V. E., Ryan, W. J., Brantly, M.
|
|
<strong>Characterization of a human alpha-1-antitrypsin null allele involving aberrant mRNA splicing.</strong>
|
|
Hum. Molec. Genet. 2: 1001-1005, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8364536" 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/2.7.1001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Ledbetter1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledbetter, S. A., Ledbetter, D. H., Ledley, F. D., Woo, S.
|
|
<strong>Localization of phenylalanine hydroxylase (PAH) and alpha-1 antitrypsin (AAT) loci in mouse genome by synteny and in situ hybridization. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 41: A173, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Lewis1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lewis, J. H., Iammarino, R. M., Spero, J. A., Hasiba, U.
|
|
<strong>Antithrombin Pittsburgh: an alpha-1-antitrypsin variant causing hemorrhagic disease.</strong>
|
|
Blood 51: 129-137, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/412531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">412531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=412531" 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="97" class="mim-anchor"></a>
|
|
<a id="Lieberman1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lieberman, J., Borhani, N. O., Feinleib, M.
|
|
<strong>Alpha-1-antitrypsin deficiency in twins and parents-of-twins.</strong>
|
|
Clin. Genet. 15: 29-36, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/310370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">310370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=310370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1979.tb02026.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Long1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W., Kurachi, K.
|
|
<strong>Complete sequence of the cDNA for human alpha-1-antitrypsin and the gene for the S variant.</strong>
|
|
Biochemistry 23: 4828-4837, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6093867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6093867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6093867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00316a003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Lopez1964" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lopez, V., Oetliker, O., Colombo, J. P., Butler, R.
|
|
<strong>Ein Fall von familiaerem alpha-1-Antitrypsinmangel.</strong>
|
|
Helv. Paediat. Acta 19: 296-303, 1964.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14229909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14229909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14229909" 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="100" class="mim-anchor"></a>
|
|
<a id="Lovegrove1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lovegrove, J. U., Jeremiah, S., Gillett, G. T., Temple, I. K., Povey, S., Whitehouse, D. B.
|
|
<strong>A new alpha 1-antitrypsin mutation, thr-met 85, (PI Z-Bristol) associated with novel electrophoresis properties.</strong>
|
|
Ann. Hum. Genet. 61: 385-391, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9459000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9459000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9459000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1469-1809.1997.6150385.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Martorana1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martorana, P. A., Brand, T., Gardi, C., van Even, P., de Santi, M. M., Calzoni, P., Marcolongo, P., Lungarella, G.
|
|
<strong>The pallid mouse: a model of genetic alpha-1-antitrypsin deficiency.</strong>
|
|
Lab. Invest. 68: 233-241, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8441253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8441253</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8441253" 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="102" class="mim-anchor"></a>
|
|
<a id="Matsunaga1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsunaga, E., Shiokawa, S., Nakamura, H., Maruyama, T., Tsuda, K., Fukumaki, Y.
|
|
<strong>Molecular analysis of the gene of the alpha-1-antitrypsin deficiency variant, M(Nichinan).</strong>
|
|
Am. J. Hum. Genet. 46: 602-612, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2309708" 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="103" class="mim-anchor"></a>
|
|
<a id="Morgan1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan, K., Scobie, G., Kalsheker, N. A.
|
|
<strong>Point mutation in a 3-prime flanking sequence of the alpha-1-antitrypsin gene associated with chronic respiratory disease occurs in a regulatory sequence.</strong>
|
|
Hum. Molec. Genet. 2: 253-257, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499914" 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/2.3.253" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Munch2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Munch, J., Standker, L., Adermann, K., Schulz, A., Schindler, M., Chinnadurai, R., Pohlmann, S., Chaipan, C., Biet, T., Peters, T., Meyer, B., Wilhelm, D., Lu, H., Jing, W., Jiang, S., Forssmann, W.-G., Kirchhoff, F.
|
|
<strong>Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide.</strong>
|
|
Cell 129: 263-275, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17448989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17448989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17448989" 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.cell.2007.02.042" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="105" class="mim-anchor"></a>
|
|
<a id="Nakamura1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakamura, H., Ogawa, A., Hisano, S., Fukuma, M., Tachibana, N., Tsuda, K.
|
|
<strong>A family with a new deficient variant of alpha-1-antitrypsin PiM(Nichinan): with special reference to diastase-resistant, periodic acid-Schiff positive globules in the liver cells.</strong>
|
|
J. Jpn. Soc. Intern. Med. 69: 47-54, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6162902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6162902</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6162902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2169/naika.69.967" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Nukiwa1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Brantly, M., Garver, R., Paul, L., Courtney, M., LeCocq, J.-P., Crystal, R. G.
|
|
<strong>Evaluation of 'at risk' alpha-1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes.</strong>
|
|
J. Clin. Invest. 77: 528-537, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484754</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3484754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112333" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Nukiwa1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Brantly, M. L., Ogushi, F., Fells, G. A., Crystal, R. G.
|
|
<strong>Characterization of the gene and protein of the common alpha-1-antitrypsin normal M2 allele.</strong>
|
|
Am. J. Hum. Genet. 43: 322-330, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901226</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2901226" 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="108" class="mim-anchor"></a>
|
|
<a id="Nukiwa1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Satoh, K., Brantly, M. L., Ogushi, F., Fells, G. A., Courtney, M., Crystal, R. G.
|
|
<strong>Identification of a second mutation in the protein-coding sequence of the Z type alpha-1-antitrypsin gene.</strong>
|
|
J. Biol. Chem. 261: 15989-15994, 1986. Note: Erratum: J. Biol. Chem. 262: 10412 only, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3491072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3491072</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3491072" 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="109" class="mim-anchor"></a>
|
|
<a id="Nukiwa1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Takahashi, H., Brantly, M., Courtney, M., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin null (Granite Falls), a nonexpressing alpha-1-antitrypsin gene associated with a frameshift to stop mutation in a coding exon.</strong>
|
|
J. Biol. Chem. 262: 11999-12004, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3040726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3040726</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3040726" 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="110" class="mim-anchor"></a>
|
|
<a id="Okayama1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okayama, H., Brantly, M., Holmes, M., Crystal, R. G.
|
|
<strong>Characterization of the molecular basis of the alpha-1-antitrypsin F allele.</strong>
|
|
Am. J. Hum. Genet. 48: 1154-1158, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2035534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2035534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2035534" 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="111" class="mim-anchor"></a>
|
|
<a id="Owen1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Owen, M. C., Brennan, S. O., Lewis, J. H., Carrell, R. W.
|
|
<strong>Mutation of antitrypsin to antithrombin: alpha-1-antitrypsin Pittsburgh (358 met-to-arg), a fatal bleeding disorder.</strong>
|
|
New Eng. J. Med. 309: 694-698, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6604220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6604220</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6604220" 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/NEJM198309223091203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Owen1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Owen, M. C., Carrell, R. W., Brennan, S. O.
|
|
<strong>The abnormality of the S variant of human alpha-1-antitrypsin.</strong>
|
|
Biochim. Biophys. Acta 453: 257-261, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1087161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1087161</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1087161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0005-2795(76)90271-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="113" class="mim-anchor"></a>
|
|
<a id="Owen1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Owen, M. C., Carrell, R. W.
|
|
<strong>Alpha-1-antitrypsin: molecular abnormality of S variant.</strong>
|
|
Brit. Med. J. 1: 130-131, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1082356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1082356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1082356" 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.1.6002.130-a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="114" class="mim-anchor"></a>
|
|
<a id="Pearson1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pearson, S., Tetri, P., George, D. L., Francke, U.
|
|
<strong>Alpha-1-antitrypsin (PI) expression in rat hepatoma-human somatic cell hybrids: evidence for PI locus on chromosome 14 and for regulatory locus on the X chromosome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 33: 148A, 1981.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="115" class="mim-anchor"></a>
|
|
<a id="Perlino1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Perlino, E., Cortese, R., Ciliberto, G.
|
|
<strong>The human alpha-1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes.</strong>
|
|
EMBO J. 6: 2767-2771, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3500042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3500042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3500042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1987.tb02571.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="116" class="mim-anchor"></a>
|
|
<a id="Poller1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poller, W., Faber, J.-P., Weidinger, S., Olek, K.
|
|
<strong>DNA polymorphisms associated with a new alpha-1-antitrypsin PI Q0 variant (PI Q0-Riedenburg).</strong>
|
|
Hum. Genet. 86: 522-524, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673114</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673114" 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/BF00194647" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="117" class="mim-anchor"></a>
|
|
<a id="Poller1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poller, W., Meisen, C., Olek, K.
|
|
<strong>DNA polymorphisms of the alpha-1-antitrypsin gene region in patients with chronic obstructive pulmonary disease.</strong>
|
|
Europ. J. Clin. Invest. 20: 1-7, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1969347" 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.1365-2362.1990.tb01769.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="118" class="mim-anchor"></a>
|
|
<a id="Roychoudhury1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roychoudhury, A. K., Nei, M.
|
|
<strong>Human Polymorphic Genes: World Distribution.</strong>
|
|
New York: Oxford Univ. Press (pub.) 1988. Pp. 132-135.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="119" class="mim-anchor"></a>
|
|
<a id="Satoh1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Satoh, K., Nukiwa, T., Brantly, M., Garver, R. I., Jr., Hofker, M., Courtney, M., Crystal, R. G.
|
|
<strong>Emphysema associated with complete absence of alpha-1-antitrypsin in serum and the homozygous inheritance of a stop codon in an alpha-1-antitrypsin-coding exon.</strong>
|
|
Am. J. Hum. Genet. 42: 77-83, 1988. Note: Erratum: Am. J. Hum. Genet. 42: 789 only, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3257351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3257351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3257351" 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="120" class="mim-anchor"></a>
|
|
<a id="Schapira1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schapira, M., Ramus, M.-A., Jallat, S., Carvallo, D., Courtney, M.
|
|
<strong>Recombinant alpha-1-antitrypsin Pittsburgh (met-358 to arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment.</strong>
|
|
J. Clin. Invest. 77: 635-637, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3484756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112347" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="121" class="mim-anchor"></a>
|
|
<a id="Schroeder1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schroeder, W. T., Miller, M. F., Woo, S. L. C., Saunders, G. F.
|
|
<strong>Chromosomal localization of the human alpha-antitrypsin gene (PI) to 14q31-32.</strong>
|
|
Am. J. Hum. Genet. 37: 868-872, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3876766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3876766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3876766" 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="122" class="mim-anchor"></a>
|
|
<a id="Scott1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scott, C. F., Carrell, R. W., Glaser, C. B., Kueppers, F., Lewis, J. H., Colman, R. W.
|
|
<strong>Alpha-1-antitrypsin-Pittsburgh: a potent inhibitor of human plasma factor XIa, kallikrein, and factor XII.</strong>
|
|
J. Clin. Invest. 77: 631-634, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484755</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3484755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112346" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="123" class="mim-anchor"></a>
|
|
<a id="Sefton1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sefton, L., Kearney, P., Kelsey, G., Povey, S., Wolfe, J.
|
|
<strong>Physical linkage of the genes PI and AACT. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1076, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="124" class="mim-anchor"></a>
|
|
<a id="Seixas2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seixas, S., Mendonca, C., Costa, F., Rocha, J.
|
|
<strong>Alpha-1-antitrypsin null alleles: evidence for the recurrence of the L353fsX376 mutation and a novel G-to-A transition in position +1 of intron IC affecting normal mRNA splicing.</strong>
|
|
Clin. Genet. 62: 175-180, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2002.620212.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="125" class="mim-anchor"></a>
|
|
<a id="Seri1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seri, M., Magi, B., Cellesi, C., Olia, P. M., Renieri, A., De Marchi, M.
|
|
<strong>Molecular characterization of the P and I variants of alpha-1-antitrypsin.</strong>
|
|
Int. J. Clin. Lab. Res. 22: 119-121, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1504305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1504305</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1504305" 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/BF02591409" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="126" class="mim-anchor"></a>
|
|
<a id="Shapiro2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shapiro, L., Pott, G. B., Ralston, A. H.
|
|
<strong>Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1.</strong>
|
|
FASEB J. 15: 115-122, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11149899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11149899</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11149899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1096/fj.00-0311com" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="127" class="mim-anchor"></a>
|
|
<a id="Sifers1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sifers, R. N., Brashears-Macatee, S., Kidd, V. J., Muensch, H., Woo, S. L. C.
|
|
<strong>A frameshift mutation results in a truncated alpha-1-antitrypsin that is retained within the rough endoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 263: 7330-7335, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3259232" 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="128" class="mim-anchor"></a>
|
|
<a id="Soutoglou2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Soutoglou, E., Talianidis, I.
|
|
<strong>Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation.</strong>
|
|
Science 295: 1901-1904, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11884757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11884757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11884757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1068356" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="129" class="mim-anchor"></a>
|
|
<a id="Takahashi1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takahashi, H., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin Null(Isola di Procida): an alpha-1-antitrypsin deficiency allele caused by deletion of all alpha-1-antitrypsin coding exons.</strong>
|
|
Am. J. Hum. Genet. 47: 403-413, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975477</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1975477" 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="130" class="mim-anchor"></a>
|
|
<a id="Takahashi1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takahashi, H., Nukiwa, T., Satoh, K., Ogushi, F., Brantly, M., Fells, G., Stier, L., Courtney, M., Crystal, R. G.
|
|
<strong>Characterization of the gene and protein of the alpha-1-antitrypsin 'deficiency' allele M(procida).</strong>
|
|
J. Biol. Chem. 263: 15528-15534, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3262617" 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="131" class="mim-anchor"></a>
|
|
<a id="Turleau1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M., Arthuis, M., Jeanson, C.
|
|
<strong>Two patients with interstitial del(14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin).</strong>
|
|
Ann. Genet. 27: 237-240, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6335371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6335371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6335371" 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="132" class="mim-anchor"></a>
|
|
<a id="van Pel2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van Pel, M., van Os, R., Velders, G. A., Hagoort, H., Heegaard, P. M. H., Lindley, I. J. D., Willemze, R., Fibbe, W. E.
|
|
<strong>Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 1469-1474, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16432201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16432201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16432201[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16432201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0510192103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="133" class="mim-anchor"></a>
|
|
<a id="Vidaud1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Emmerich, J., Alhenc-Gelas, M., Yvart, J., Fiessinger, J. N., Aiach, M.
|
|
<strong>Met358-to-arg mutation of alpha-1-antitrypsin associated with protein C deficiency in a patient with mild bleeding tendency.</strong>
|
|
J. Clin. Invest. 89: 1537-1543, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569192</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1569192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115746" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="134" class="mim-anchor"></a>
|
|
<a id="Weidinger1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weidinger, S., Jahn, W., Cujnik, F., Schwarzfischer, F.
|
|
<strong>Alpha-1-antitrypsin: evidence for a fifth PI M subtype and a new deficiency allele PI*Z(Augsburg).</strong>
|
|
Hum. Genet. 71: 27-29, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3875547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3875547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3875547" 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/BF00295662" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="135" class="mim-anchor"></a>
|
|
<a id="Weitkamp1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weitkamp, L. R., Cox, D., Guttormsen, S., Johnston, E., Hempfling, S.
|
|
<strong>Allelic specific heterogeneity in the Pi-Gm linkage group.</strong>
|
|
Cytogenet. Cell Genet. 22: 647-650, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/313312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">313312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=313312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000131044" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="136" class="mim-anchor"></a>
|
|
<a id="Welch1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Welch, S. G., McGregor, I. A., Williams, K.
|
|
<strong>Alpha-1-antitrypsin (Pi) phenotypes in a village population from the Gambia, West Africa.</strong>
|
|
Hum. Genet. 53: 233-235, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6965658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6965658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6965658" 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/BF00273503" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="137" class="mim-anchor"></a>
|
|
<a id="Whitehouse1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whitehouse, D. B., Abbott, C. M., Lovegrove, J. U., McIntosh, I., McMahon, C. J., Mieli-Vergani, G., Mowat, A. P., Hopkinson, D. A.
|
|
<strong>Genetic studies on a new deficiency gene (PI*Z-Tun) at the PI locus.</strong>
|
|
J. Med. Genet. 26: 744-749, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2575668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2575668</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2575668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.26.12.744" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="138" class="mim-anchor"></a>
|
|
<a id="Wilkie1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M.
|
|
<strong>The molecular basis of genetic dominance.</strong>
|
|
J. Med. Genet. 31: 89-98, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8182727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8182727</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8182727" 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.31.2.89" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="139" class="mim-anchor"></a>
|
|
<a id="Yamamoto1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamamoto, Y., Sawa, R., Okamoto, N., Matsui, A., Yanagisawa, M., Ikemoto, S.
|
|
<strong>Deletion 14q(q24.3 to q32.1) syndrome: significance of peculiar facial appearance in its diagnosis, and deletion mapping of Pi (alpha-1-antitrypsin).</strong>
|
|
Hum. Genet. 74: 190-192, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3490426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3490426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3490426" 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/BF00282092" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="140" class="mim-anchor"></a>
|
|
<a id="Yoshida1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Chillar, R., Taylor, J. C.
|
|
<strong>An alpha-1-antitrypsin variant, PiB Alhambra (lys-to-asp, glu-to-asp), with rapid anodal electrophoretic mobility.</strong>
|
|
Am. J. Hum. Genet. 31: 555-563, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/315708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">315708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=315708" 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="141" class="mim-anchor"></a>
|
|
<a id="Yoshida1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Ewing, C., Wessels, M., Lieberman, J., Gaidulis, L.
|
|
<strong>Molecular abnormality of Pi S variant of human alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 29: 233-239, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/301355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">301355</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=301355" 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="142" class="mim-anchor"></a>
|
|
<a id="Yoshida1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Lieberman, J., Gaidulis, L., Ewing, C.
|
|
<strong>Molecular abnormality of human alpha-1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency.</strong>
|
|
Proc. Nat. Acad. Sci. 73: 1324-1328, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1083527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1083527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1083527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.73.4.1324" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="143" class="mim-anchor"></a>
|
|
<a id="Yoshida1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Taylor, J. C., Van den Brock, W. G. M.
|
|
<strong>Structural difference between the normal PiM(1) and the common PiM(2) variant of human alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 31: 564-568, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/315709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">315709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=315709" 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="144" class="mim-anchor"></a>
|
|
<a id="Yuasa1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yuasa, I., Sugimoto, Y., Ichinose, M., Matsumoto, Y., Fukumaki, Y., Sasaki, T., Okada, K.
|
|
<strong>PI*S(Iiyama), a deficiency gene of alpha-1-antitrypsin: evidence for the occurrence in western Japan.</strong>
|
|
Jpn. J. Hum. Genet. 38: 185-191, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8358043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8358043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8358043" 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/BF01883709" 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">
|
|
Bao Lige - updated : 11/06/2024
|
|
</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">
|
|
Bao Lige - updated : 08/31/2022<br>Patricia A. Hartz - updated : 7/11/2012<br>Ada Hamosh - updated : 9/7/2011<br>Ada Hamosh - updated : 8/17/2010<br>Cassandra L. Kniffin - updated : 1/13/2009<br>Paul J. Converse - updated : 8/17/2007<br>Paul J. Converse - updated : 3/24/2006<br>Victor A. McKusick - updated : 1/20/2006<br>Paul J. Converse - updated : 3/14/2005<br>Victor A. McKusick - updated : 12/4/2003<br>Victor A. McKusick - updated : 7/10/2003<br>Ada Hamosh - updated : 4/15/2003<br>Victor A. McKusick - updated : 11/26/2002<br>Victor A. McKusick - updated : 6/3/2002<br>Ada Hamosh - updated : 4/2/2002<br>Victor A. McKusick - updated : 2/12/2002<br>Victor A. McKusick - updated : 1/10/2002<br>Victor A. McKusick - updated : 10/21/1999<br>Victor A. McKusick - updated : 12/10/1998<br>Victor A. McKusick - updated : 11/5/1998<br>Victor A. McKusick - updated : 7/10/1998<br>Cynthia K. Ewing - updated : 10/23/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 11/06/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/30/2022<br>mgross : 08/31/2022<br>carol : 07/20/2016<br>carol : 07/18/2016<br>carol : 7/15/2016<br>carol : 7/14/2016<br>carol : 7/9/2016<br>carol : 7/9/2016<br>alopez : 8/7/2013<br>carol : 5/21/2013<br>terry : 4/4/2013<br>terry : 3/15/2013<br>carol : 8/15/2012<br>terry : 8/8/2012<br>terry : 7/11/2012<br>carol : 5/30/2012<br>terry : 10/10/2011<br>mgross : 10/3/2011<br>alopez : 9/8/2011<br>terry : 9/7/2011<br>terry : 9/7/2010<br>terry : 9/7/2010<br>terry : 9/7/2010<br>alopez : 8/18/2010<br>joanna : 8/17/2010<br>terry : 8/17/2010<br>carol : 8/13/2010<br>carol : 9/15/2009<br>terry : 6/3/2009<br>wwang : 4/1/2009<br>wwang : 1/16/2009<br>ckniffin : 1/13/2009<br>terry : 1/8/2009<br>terry : 1/8/2009<br>terry : 1/7/2009<br>terry : 1/7/2009<br>carol : 10/4/2007<br>mgross : 8/17/2007<br>mgross : 3/29/2006<br>terry : 3/24/2006<br>carol : 2/14/2006<br>alopez : 1/25/2006<br>terry : 1/20/2006<br>carol : 11/28/2005<br>mgross : 3/14/2005<br>mgross : 3/14/2005<br>mgross : 3/17/2004<br>alopez : 12/10/2003<br>terry : 12/4/2003<br>carol : 11/24/2003<br>carol : 7/21/2003<br>terry : 7/10/2003<br>alopez : 4/17/2003<br>terry : 4/15/2003<br>cwells : 11/26/2002<br>terry : 11/20/2002<br>cwells : 6/26/2002<br>terry : 6/3/2002<br>carol : 4/25/2002<br>alopez : 4/5/2002<br>terry : 4/2/2002<br>terry : 3/13/2002<br>terry : 2/12/2002<br>cwells : 1/25/2002<br>cwells : 1/16/2002<br>terry : 1/10/2002<br>alopez : 11/23/1999<br>carol : 10/21/1999<br>carol : 12/16/1998<br>terry : 12/10/1998<br>carol : 11/16/1998<br>terry : 11/5/1998<br>dkim : 7/24/1998<br>dkim : 7/24/1998<br>carol : 7/15/1998<br>terry : 7/10/1998<br>terry : 5/29/1998<br>terry : 1/29/1998<br>mark : 10/14/1997<br>mark : 10/14/1997<br>dholmes : 8/14/1997<br>alopez : 7/31/1997<br>jenny : 7/9/1997<br>joanna : 7/3/1997<br>joanna : 6/24/1997<br>terry : 1/10/1997<br>mark : 12/29/1996<br>jamie : 10/23/1996<br>jamie : 10/16/1996<br>jamie : 10/14/1996<br>mark : 3/25/1996<br>terry : 7/10/1995<br>mark : 6/13/1995<br>pfoster : 5/2/1995<br>davew : 8/18/1994<br>jason : 6/17/1994<br>warfield : 4/4/1994
|
|
</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> 107400
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SERPIN PEPTIDASE INHIBITOR, CLADE A, MEMBER 1; SERPINA1
|
|
|
|
</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">
|
|
ALPHA-1-ANTITRYPSIN; AAT<br />
|
|
PROTEASE INHIBITOR 1; PI<br />
|
|
PI1<br />
|
|
ANTI-ELASTASE<br />
|
|
ANTITRYPSIN
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SERPINA1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 14q32.13
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 14:94,376,747-94,390,635 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
14q32.13
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Emphysema due to AAT deficiency
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613490
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Emphysema-cirrhosis, due to AAT deficiency
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613490
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hemorrhagic diathesis due to antithrombin Pittsburgh
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613490
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The SERPINA1 gene encodes alpha-1-antitrypsin (AAT), also known as protease inhibitor (PI), a major plasma serine protease inhibitor. AAT complexes predominantly with elastase, but also with trypsin, chymotrypsin, thrombin, and bacterial proteases. The most important inhibitory action of AAT is that against neutrophil elastase (ELANE, or HLE; 130130), a protease that degrades elastin of the alveolar walls as well as other structural proteins of a variety of tissues (review by Cox, 2001).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kurachi et al. (1981) cloned a nearly full-length baboon AAT cDNA (approximately 1,352 bp) and a partial human AAT cDNA (approximately 306 bp). They found more than 96% homology between the cDNA and predicted amino acid sequences of AAT in the 2 species. Comparison of baboon AAT, human antithrombin III (107300), and chicken ovalbumin indicated about 30% homology of amino acid sequence. </p><p>Long et al. (1984) cloned a full-length human AAT cDNA from a liver cDNA library. Sequence analysis revealed a precursor molecule containing a 24-amino acid signal peptide and a mature protein of 394 amino acids. AAT is primarily synthesized in the liver. </p><p>Crystal (1990) noted that hepatocytes are the major source of AAT, but that the gene is also expressed in mononuclear phagocytes and neutrophils. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lai et al. (1983) showed that the AAT gene contains 3 introns in the peptide-coding region. </p><p>Long et al. (1984) found that the genomic length of the PI gene is 10.2 kb with a 1,434-bp coding region. The gene has 4 introns; exon 1, the 5-prime portion of exon 2, and the 3-prime portion of exon 5 are noncoding regions. The first intron, 5.3 kb long, contains a 143-amino acid open reading frame (which does not appear to be an actual protein coding region), an Alu family sequence, and a pseudotranscription initiation region. </p><p>Perlino et al. (1987) found that the AAT gene in macrophages is transcribed from a macrophage-specific promoter located about 2,000 bp upstream of the hepatocyte-specific promoter. Transcription from the 2 AAT promoters is mutually exclusive; the macrophage promoter is silent in hepatocytes and the hepatocyte promoter is silent in macrophages. In macrophages, 2 distinct mRNAs are generated by alternative splicing. </p><p>Hafeez et al. (1992) demonstrated that the AAT gene has 3 macrophage-specific transcriptional initiation sites upstream from a single hepatocyte-specific transcriptional initiation site. Macrophages use these sites during basal and modulated expression. Hepatoma cells use the hepatocyte-specific transcriptional initiation site during basal and modulated expression but also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by the acute phase mediator interleukin-6 (IL6; 147620). </p><p>Soutoglou and Talianidis (2002) analyzed the ordered recruitment of factors to the human alpha-1-antitrypsin promoter around the initial activation of the gene during enterocyte differentiation. They found that a complete preinitiation complex, including phosphorylated RNA Pol II (180660), was assembled at the promoter long before transcriptional activation. The histone acetyltransferases CBP (600140) and P/CAF (602303) were recruited subsequently, but local histone hyperacetylation was delayed. After transient recruitment of the human Brahma homolog BRM (600014), remodeling of the neighboring nucleosome coincided with transcription initiation. Soutoglou and Talianidis (2002) concluded that, at this promoter, chromatin reconfiguration is a defining step of the initiation process, acting after the assembly of the Pol II machinery. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lai et al. (1983) used a cloned AAT gene as a hybridization probe to analyze EcoRI-digested genomic DNA from different individuals and identified 2 distinct bands (9.6 kb and 8.5 kb long) in every case. Analysis using only intronic DNA as probe showed that the authentic gene resides in the 9.6-kb fragment. The 8.5-kb fragment was thought to contain a gene with close sequence homology to that of AAT. </p><p>By studying hybrids of mouse or rat hepatoma cells with human lymphocytes, Darlington et al. (1982) and Pearson et al. (1981) achieved direct assignment of the PI locus to chromosome 14. From study of 2 families with abnormalities of the long arm of chromosome 14, Cox et al. (1982) localized GM to 14q32.3 and PI to a more proximal position between 14q24.3 and 14q32.1. The immunoglobulin genes are in a chromosome region noted for its high frequency of breaks associated with chromosome rearrangement, occurring both spontaneously in cultured lymphocytes and in certain malignancies. </p><p>By in situ hybridization, Schroeder et al. (1985) narrowed the assignment of the PI locus to 14q31-q32. Turleau et al. (1984) studied a patient with an interstitial deletion of 14q and assigned the PI locus to 14q32.1 by exclusion mapping. In a similar patient with an interstitial deletion of 14q, Yamamoto et al. (1986) confirmed the assignment to 14q32.1. By the dosage principle, the level of alpha-1-antitrypsin in the patient was only about half of that in his parents and in controls. </p><p>Sefton et al. (1989) used pulsed field gel electrophoresis to demonstrate that the genes encoding alpha-1-antitrypsin and alpha-1-antichymotrypsin (AACT, SERPINA3; 107280) are approximately 220 kb apart and oriented in opposite directions.</p><p>Molecular studies of a ring chromosome 14 showed that the IGH and D14S1 loci were missing, whereas the PI locus was present (Keyeux et al., 1989). Thus, PI is proximal to the other 2 loci, a conclusion that was supported by much earlier data. A noncoding alpha-1-antitrypsin-like gene (PIL; 107410) is located 12 kb 3-prime of the AAT gene. Billingsley et al. (1989) found that this gene and the AAT and AACT genes are carried by a single 550-kb NarI fragment. Also see Billingsley et al. (1993). </p><p>By in situ hybridization, Ledbetter et al. (1987) localized the AAT locus to mouse chromosome 12.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Dycaico et al. (1988) established transgenic mouse lineages that carried the normal (M) (see 107400.0001) or mutant (Z) (107400.0011) alleles of the human AAT gene. All expressed the human protein in liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, particularly in hepatocytes, and was found in serum in concentrations 10 times lower than the M-allele protein. Mice in one lineage carrying the Z allele displayed significant runting in the neonatal period and had developed abnormalities in the liver with accumulation of human Z protein in diastase-resistant cytoplasmic globules that stained with periodic acid-Schiff reaction (PAS). </p><p>The major physiologic substrate of alpha-1-antitrypsin is elastase, particularly in the lower respiratory tract (Cox, 2001).</p><p>AAT is an acute-phase reactant in that serum levels are increased with inflammation, trauma, and pregnancy (Cox, 1989).</p><p><strong><em>Alpha-1-Antitrypsin Deficiency</em></strong></p><p>
|
|
Deficiency of alpha-1-antitrypsin (613490) is primarily associated with the risk of emphysema and liver disease; see MOLECULAR GENETICS.</p><p><strong><em>Role in Twinning</em></strong></p><p>
|
|
Lieberman et al. (1979) found an increased frequency of heterozygosity for antitrypsin deficiency in twins and parents of twins. They concluded that 'increased' fertility and twinning may be heterozygous advantages for antitrypsin deficiency. Clark and Martin (1982) found that the frequency of the S allele (107400.0013) in mothers of dizygotic twins (0.088) was double that in controls (0.044). The frequency of S in the parents of monozygotic twins and in fathers of DZ twins was no higher than in controls. Normal frequencies were observed for the Z allele (107400.0011). No fertility indices other than twinning itself were available. To study relationships between Pi types, fertility, and twinning, Boomsma et al. (1992) studied 90 DZ and 70 MZ Dutch twin pairs and their parents. They found that mothers of dizygotic twins had frequencies of the S and Z alleles that were 3 times higher than those in a control sample. Mothers of identical twins also had a higher frequency of S than controls. The S allele may thus both increase ovulation rate and enhance the success of multiple pregnancies. </p><p><strong><em>Role in Human Immunodeficiency Virus-1 Infection</em></strong></p><p>
|
|
Bristow (2001) found that decreased human immunodeficiency virus (HIV) infectivity correlated significantly with decreased cell surface expression of leukocyte (neutrophil) elastase (HLE) on monocytes but not lymphocytes. Decreased levels of PI correlated with increased cell surface HLE expression and increased HIV infectivity. </p><p>Bristow et al. (2001) showed that decreased HIV viral load correlated with decreased circulating PI. Furthermore, asymptomatic patients manifested deficient levels of active PI. Bristow et al. (2001) noted that deficient levels of PI lead to degenerative lung diseases and suggested that preventing PI deficiency may prevent HIV-associated pathophysiology. </p><p>Using subclones of monocytic cell lines, Bristow et al. (2003) showed that HLE localized to the cell surface, but not granules, of HIV-1-permissive clones, and to the granules, but not the cell surface, of HIV-1-nonpermissive clones. Stimulation of nonpermissive clones with lipopolysaccharide and LBP (151990), followed by exogenous PI, induced cell surface HLE expression, resulting in susceptibility to HIV infection. PI appeared to promote HIV coreceptor colocalization with surface HLE, thus permitting HIV infectivity. </p><p>Shapiro et al. (2001) showed that, at physiologic concentrations, AAT and CE-2072, a synthetic inhibitor of neutrophil elastase and proteinase-3 (PRTN3; 177020), inhibited HIV-1 production in chronically infected monocytic cell lines, in fresh blood mononuclear cells infected after an activation step, and in permissive HeLa cells. EMSA analysis indicated that AAT suppressed activation of the HIV-1-inducing transcription factor NFKB (see 164011). In 5 individuals with the Z-type AAT mutation (glu342lys; 107400.0011), HIV-1 p24 antigen increased more than 6-fold in whole blood after infection with a monocyte-tropic HIV strain. In contrast, there was no significant increase in blood obtained from healthy volunteers. </p><p>By screening a peptide library generated from hemofiltrate, Munch et al. (2007) identified a 20-amino acid peptide from the C-proximal region of alpha-1-antitrypsin, designated virus-inhibitory peptide (VIRIP), as the most potent inhibitor of multiple HIV-1 strains, including those resistant to antiviral drugs. Changes in some VIRIP residues increased its antiviral potency 100-fold. VIRIP blocked HIV-1 entry by interacting with the virus gp41 fusion peptide. Munch et al. (2007) proposed that VIRIP may affect disease progression in HIV-1-infected individuals. </p><p><strong><em>NET Inhibitory Peptides</em></strong></p><p>
|
|
Neonatal neutrophils fail to form neutrophil extracellular traps (NETs) due to circulating NET inhibitory peptides (NIPs), which are cleavage fragments of A1AT. Using immunofluorescence assays, Campbell et al. (2021) showed that human placenta from both term and preterm pregnancies secreted serine protease A1 (HTRA1; 602194) into fetal circulation. Plasma HTRA1 levels were reduced after delivery, and decreased HTRA1 plasma levels were associated with decreased levels of NIPs. Placental HTRA1 cleaved A1AT after amino acid 382 to generate a C-terminal cleavage fragment of A1AT, termed A1ATM383S-CF, that could inhibit NET formation in vitro. Through NET inhibition, A1ATM383S-CF decreased bacterial killing, but it maintained other key neutrophil activities in vitro. In vivo analysis with wildtype mice showed that mouse placenta also secreted Htra1, and placental Htra1 cleaved A1at to generate A1atM383S-CF and inhibit NET formation by neonatal neutrophils. Analysis with Htra1 -/- and wildtype mice revealed that inhibition of NET formation during experimental neonatal sepsis improved survival. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Fagerhol (1968) suggested that the system of inherited AAT variants be called Pi for protease inhibitor. Cox (1978) reported the recommendations of a workshop on PI nomenclature. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Many electrophoretic variants of serum alpha-1-antitrypsin have been described, beginning with those reported by Axelsson and Laurell (1965). Kueppers and Bearn (1967) studied an Italian family with multiple members heterozygous for an electrophoretic variant that could not be distinguished from that which Axelsson and Laurell (1965) found in a Swedish family. </p><p>About 30 variants of alpha-1-antitrypsin had been described by 1981 (Hug et al., 1981). The alleles were given symbols according to the relative electrophoretic mobility of the allele product. </p><p>Cox et al. (1987) studied RFLPs associated with the AAT gene. They gave information on extensive variability expressed by the polymorphic information content (PIC) as proposed by Botstein et al. (1980). PI types and M subtypes tended to be associated with specific RFLP haplotypes. </p><p>Nukiwa et al. (1988) indicated that approximately 75 AAT alleles had been identified at the protein and/or gene level. </p><p>Roychoudhury and Nei (1988) tabulated worldwide gene frequencies for allelic variants M (M1, M2, M3, M4), S, Z, F, I, and V. Cox (1989) and Crystal (1989) reviewed the variants, 'normal' and pathologic, of the PI gene. </p><p><strong><em>'Normal' Alleles</em></strong></p><p>
|
|
Crystal (1989) listed 10 normal AAT alleles that had been sequenced (107400.0001-107400.0010). </p><p>Nukiwa et al. (1988) stated that the most common alleles are the 2 forms of M1, that with valine at position 213 (M1V; 107400.0002) and that with alanine at position 213 (M1A; 107400.0001). </p><p><strong><em>'Risk' Alleles</em></strong></p><p>
|
|
Crystal (1989) divided AAT 'at risk' alleles into 'deficiency' alleles and 'null' alleles. He stated that except for the rare Pittsburgh allele (107400.0026), which is associated with a bleeding disorder, only those phenotypes comprising 2 'at risk' alleles place the individual at risk for development of disease. Alleles in the 'at risk' class are found almost exclusively among Caucasians of European descent, with the highest frequency in northern Europe. Blacks and Asians are rarely affected. </p><p>The most common AAT deficiency allele is the Z allele (glu342-to lys; 107400.0011), which occurs on an M1A (ala213; 107400.0001) haplotype background (Nukiwa et al., 1986). The homozygous ZZ phenotype is associated with a high risk of both emphysema and liver disease. The Z allele reaches polymorphic frequencies in Caucasians and is rare or absent in Asians and blacks (DeCroo et al., 1991; Hutchison, 1998). </p><p>Clark et al. (1982) reported the cases of 2 brothers with Weber-Christian panniculitis and the AAT Z phenotype. A younger brother had the Z phenotype without Weber-Christian disease. Along with several earlier reported cases, these observations establish a relationship. </p><p>Another common AAT deficiency allele is the S allele (glu264-to-val; 107400.0013), which occurs on an M1V (val213; 107400.0002) haplotype background. Pi*S homozygotes are at no risk of emphysema, but compound heterozygotes with a Z or a null allele have a mildly increased risk (Curiel et al., 1989). The S allele reaches polymorphic frequencies in Caucasians and is rare or absent in Asians and blacks. It is not associated with liver disease. </p><p>Other rare deficiency AAT alleles may result in increased risk for both liver and lung disease (e.g., Pi M(Malton); 107400.0012) or only emphysema (e.g., Pi M(Procida); 107400.0016). Some of the rare deficiency alleles have been found in Japanese (e.g., Pi S(Iiyama); 107400.0039).</p><p>Null AAT alleles are rare but have been found in all populations. Garver et al. (1986) investigated the molecular basis of the Pi null-null AAT phenotype. The gene appeared to be intact without discernible deletion or other structural abnormality, yet there was no detectable mRNA produced. The 5-prime promoter region also appeared to be normal. No evidence of hypermethylation of cytosine nucleotides in the promoter region was detected. The defect may be comparable to that in some forms of thalassemia in which a change, at a splicing site, for example, may lead to greatly reduced mRNA production. The null-null phenotype is accompanied by emphysema as is the ZZ and SZ phenotypes but an important difference is that cirrhosis and liver disease do not occur with the null-null phenotype; there is no abnormal antitrypsin produced that is excreted with difficulty from the cells of synthesis. </p><p>Nukiwa et al. (1987) identified a null form of alpha-1-antitrypsin resulting from a frameshift causing a stop codon to be formed approximately 44% from the N terminus of the precursor protein (Null(Granite Falls); 107400.0020). Although the molecular basis of antitrypsin deficiency was quite different from that in the Z haplotype, the phenotypic consequences were similar: severe deficiency associated with high risk of emphysema. </p><p>Seixas et al. (2002) reported 2 null alleles of the PI gene in Portuguese patients with emphysema. These alleles were associated with total lack of circulating protein as indicated by the absence of isoelectric focusing banding patterns. One of the alleles, designated Q0(Ourem), was identical to Q0(Mattawa) on an M3 normal background (107400.0022). The second allele, Q0(Porto), had a novel mutation which restricted mononuclear phagocyte transcripts to mRNA species resulting from the direct splice of exon IA to exon II. The absence of this normal splice alternative in the liver, where PI is primarily synthesized, provided a basis for the pathogenic effects of this mutation. </p><p><strong><em>PI Pittsburgh</em></strong></p><p>
|
|
The PI Pittsburgh allele (met358-to-arg; 107400.0026), which occurs at the AAT active site, is an example of a mutation leading to altered function of the gene product. AAT becomes a potent inhibitor of thrombin and factor XI rather than of elastase. The mutation results in a bleeding disorder (Lewis et al., 1978; Owen et al., 1983). </p><p><strong><em>SERPINA1 Haplotypes Associated with Chronic Obstructive Pulmonary Disease</em></strong></p><p>
|
|
While cigarette smoking is a major cause of COPD (see 606963), only 15% of smokers develop the disease, indicating major genetic influences. The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 (107280) may also play a role. Chappell et al. (2006) identified 15 single-nucleotide polymorphism (SNP) haplotype tags from high-density SNP maps of the 2 genes and evaluated these SNPs in the largest case-control genetic study of COPD conducted to that time. For SERPINA1, 6 newly identified haplotypes with a common backbone of 5 SNPs were found to increase the risk of disease by 6- to 50-fold, the highest risk of COPD that had been reported. In contrast, no haplotype associations for SERPINA3 were identified. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>DeCroo et al. (1991) studied the frequency of alpha-1-antitrypsin alleles in US whites, US blacks, and African blacks (living in Nigeria). While the PI*S allele was present at a polymorphic level in US whites, it was present only sporadically in US blacks and completely absent in African blacks. The PI*Z allele was not detected in the black populations tested. DeCroo et al. (1991) used the PI allele frequency data to calculate white admixture in US blacks. The average white admixture estimate in US blacks, based on all PI alleles, was about 13%. This value was about 24% when only the S and Z alleles were used. </p><p>Studies of the distribution of the S and Z alleles in Europe demonstrated that they occur mainly among those of European stock. Hutchison (1998) found that the frequency of the gene for PiZ is highest on the northwestern seaboard of the continent and that the mutation seems to have arisen in southern Scandinavia. The distribution of PiS is quite different: the gene frequency is highest in the Iberian peninsula and the mutation is likely to have arisen in that region. </p><p>By means of a metaanalysis of 43 studies, Blanco et al. (2001) analyzed the distribution of the PI*S and PI*Z alleles in countries outside Europe and compared them with data from Europe. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The pallid (pa) (604310) mouse develops emphysema late in life. Martorana et al. (1993) demonstrated that pallid mice have markedly reduced levels of serum alpha-1-antitrypsin associated with severe deficiency in serum elastase inhibitory capacity. However, they have normal alpha-1-antitrypsin mRNA levels in the liver. </p><p>Green et al. (2003) showed that Drosophila 'necrotic' (nec) mutations can mimic alpha-1-antitrypsin deficiency. They identified 2 nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an amino acid substitution equivalent to that found in S(Iiyama) variant antitrypsin (107400.0039) failed to complement nec-null mutations and demonstrated a dominant temperature-dependent inactivation of the wildtype nec allele. Green et al. (2003) concluded that the Drosophila nec system can be used as a powerful system to study serpin polymerization in vivo. </p><p>Van Pel et al. (2006) reported that IL8 (146930)- and GCSF (CSF3; 138970)-induced mobilization of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in mice was completely inhibited by total body irradiation (TBI). They found that TBI increased expression of Serpina1 mRNA and protein, which inhibited elastase activity. Inhibition of HSC/HPC mobilization in irradiated mice could be reversed by anti-Serpina1. Furthermore, injection of Serpina1, but not heat-inactivated Serpina1, prior to administration of IL8 inhibited HSC/HPC mobilization. Van Pel et al. (2006) concluded that low-dose TBI induces Serpina1 in bone marrow and inhibits HSC/HPC mobilization, and they hypothesized that cytokine-induced HSC/HPC mobilization is determined by a critical balance between serine proteases and their inhibitors. </p><p>Kamimoto et al. (2006) bred the PiZ mouse onto the GFP-LC3 background to monitor autophagy. </p><p>Hidvegi et al. (2010) demonstrated that the autophagy-enhancing drug carbamazepine decreased the hepatic load of mutant alpha-1-antitrypsin Z (ATZ) protein and hepatic fibrosis in a mouse model of AAT deficiency-associated liver disease. The mouse used was the PiZ mouse, developed by Dycaico et al. (1988), in which the human ATZ gene is a transgene. Although the PiZ mouse has normal circulating levels of endogenous murine alpha-1-antitrypsin, it is a robust model of liver disease associated with AAT deficiency, as characterized by intrahepatocytic ATZ-containing globules, inflammation, and increased regenerative activity, dysplasia, and fibrosis. Hidvegi et al. (2010) concluded that their results in this animal model provided a basis for testing carbamazepine, which has an extensive clinical safety profile in patients with AAT deficiency (613490) and also provided proof of principle for therapeutic use of autophagy enhancers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The polymorphism of prealbumin described by Fagerhol and Braend (1965) was shown by Fagerhol and Laurell (1967) to be the same as the alpha-1-antitrypsin polymorphism. </p><p>A possible heterogeneity in recombination frequency between Pi variants believed to be allelic was reported by Gedde-Dahl et al. (1972): Pi(Z) had less recombination with Gm than Pi(non-Z). Gedde-Dahl et al. (1975) gave further data on the Gm-Pi linkage. They considered heterogeneity of recombination fraction among males of different Pi types to be likely. The major difference seemed to be between the Pi(Z) and other alleles. Possible explanations included a chromosomal deletion, inversion or locus regulating recombination in linkage disequilibrium with the Pi locus. Gedde-Dahl et al. (1981) showed that the allele-specific heterogeneity of Gm-Pi linkage is attributable to 'reduced' recombination in Z-allele heterozygotes. They found an equal sex ratio for Pi 'non-Z' variants, as opposed to a 1:2 male-female ratio for 'Z' families. The location of Gm and Pi on 6p was excluded by Bender et al. (1979). </p><p>Babron et al. (1990) confirmed a previous finding that the presence of the Pi Z allele tends to decrease the recombination rate between the GM (147100) and PI loci. This decrease appeared to be similar in both sexes and not unique in males as previously noted. The results suggested a possible linkage disequilibrium between the Pi Z allele and a large inversion between the GM and PI loci. </p><p>Carrell (1986) cited evidence for the existence of 2 genes coding for alpha-1-antitrypsin, although the plasma findings were compatible with expression of the alleles at a single locus. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>40 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PI M1-ALA213</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI, M1A
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ALA213
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs6647,
|
|
|
|
|
|
gnomAD: rs6647,
|
|
|
|
|
|
ClinVar: RCV000019553, RCV000019554, RCV000151834, RCV000406073, RCV001701482, RCV002362589
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>M1A, a normal variant, is believed to be the 'oldest' human PI allele, with the other common normal alleles M1V (107400.0002), M2 (107400.0003), and M3 (107400.0004) derived from M1A by single base substitutions. M2 is derived from M3; it has the same amino acid difference that distinguishes M3 from M1V but a second substitution in addition. The 4 common normal alleles are considered the 'base' from which all the other alleles are derived (see Fig. 4 in Crystal, 1989). The M1A allele has a frequency of 0.20-0.23 in US Caucasians. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PI M1-VAL213</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI, M1V
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ALA213
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs6647,
|
|
|
|
|
|
gnomAD: rs6647,
|
|
|
|
|
|
ClinVar: RCV000019555, RCV000019556, RCV002362590
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This normal allele has a frequency of 0.44-0.49 in US Caucasians.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PI M2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ARG101HIS ON M3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs709932,
|
|
|
|
|
|
gnomAD: rs709932,
|
|
|
|
|
|
ClinVar: RCV000019557, RCV000019559, RCV000155576, RCV000310904, RCV001636605, RCV002345248
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>M2, which has a frequency of 0.10-0.11 in US Caucasians (Cox, 1989), was studied by Nukiwa et al. (1988), who found that its coding exons are identical to those of the more frequent form of M1 (val213) except for 2 bases: a change in codon 101 from CGT to CAT, leading to an amino acid change of arginine to histidine; and a change in codon 376 from GAA to GAC, resulting in an amino acid change from glutamic acid to aspartic acid. Since 2 mutations separate these 2 common alleles, Nukiwa et al. (1988) suggested that another AAT variant (presumably M3) was an intermediate in their evolution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PI M3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLU376ASP ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1303,
|
|
|
|
|
|
gnomAD: rs1303,
|
|
|
|
|
|
ClinVar: RCV000019558, RCV000155574, RCV000380179, RCV001650837, RCV002345249
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This normal variant allele has a frequency of 0.14-0.19 among US Caucasians. Graham et al. (1990) identified a single nucleotide difference between M1 (val213) and M3: a transversion in codon 376 from GAA(glu) to GAC(asp). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PI M4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ARG101HIS ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019557, RCV000019559, RCV000155576, RCV000310904, RCV001636605, RCV002345248
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>M4, an uncommon normal allele, is likely derived by single substitution from M1V; however, it has the same mutation that changed M2 to M3, and thus it is possible that M4 derived from M3 (or vice versa).</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PI B(ALHAMBRA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ASP-LYS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019560
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Yoshida et al. (1979) found 2 amino acid substitutions in the rare antitrypsin variant PiB Alhambra. One substitution was asp for lys at an unknown location (Crystal, 1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PI F</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ARG223CYS ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28929470,
|
|
|
|
|
|
gnomAD: rs28929470,
|
|
|
|
|
|
ClinVar: RCV000019561, RCV000148879, RCV000151833, RCV000205893, RCV000622899, RCV000727618, RCV004724750
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This rare 'normal' allele has a CGT-to-TGT change in codon 223 (Crystal, 1989; Okayama et al., 1991). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 PI P(ST. ALBANS)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ASP341ASN ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs143370956, rs28929471,
|
|
|
|
|
|
gnomAD: rs143370956,
|
|
|
|
|
|
ClinVar: RCV000019562, RCV000148874, RCV000178751, RCV004748529
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In addition to a GAC-to-AAC change in codon 341, this rare 'normal' allele has a 'silent' asp256 (GAT)-to-asp256 (GAC) change. The rare P-family of AAT variants is defined by the position of migration of the protein on isoelectric focusing (IEF) of serum between the common M and S variants. The P(St. Albans) allele is associated with normal serum levels of AAT, whereas the P(Lowell) allele (107400.0019) is associated with reduced levels. Holmes et al. (1990) described the DNA change underlying both of these variants. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 PI X</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLU204LYS ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422208,
|
|
|
|
|
|
gnomAD: rs199422208,
|
|
|
|
|
|
ClinVar: RCV000019563, RCV000512615, RCV002260969
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This rare 'normal' allele has been sequenced only at the level of the protein (Crystal, 1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 PI CHRISTCHURCH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLU363LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912712,
|
|
|
|
|
|
gnomAD: rs121912712,
|
|
|
|
|
|
ClinVar: RCV000019564, RCV000201867, RCV000597262, RCV003964806
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Brennan and Carrell (1986) characterized antitrypsin Christchurch, which shows a substitution of lysine for glutamic acid at position 363. Although electrophoretic mobility of the mutant protein was abnormal, no functional abnormality of the protein was detected. The base PI allele, M1A or M1V, is unknown (Crystal, 1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 PI Z</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLU342LYS ON M1A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28929474,
|
|
|
|
|
|
gnomAD: rs28929474,
|
|
|
|
|
|
ClinVar: RCV000019567, RCV000019594, RCV000019595, RCV000148877, RCV000194811, RCV000255454, RCV000623762, RCV000768543, RCV001195107, RCV002054450, RCV002251912, RCV002276567, RCV002466247, RCV003415721
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This is the most frequent allele leading to a high risk of emphysema (and liver disease) in the homozygote; the allele frequency is 0.01-0.02 in US Caucasians (Crystal, 1989). Nukiwa et al. (1986) demonstrated the val213-to-ala substitution (here symbolized M1A) in PI*Z in addition to the disease-producing glu342-to-lys mutation. Ala213 was found in all of 40 Z haplotypes, using synthetic oligonucleotide gene probes directed toward the mutated exon 3 sequences in the Z gene. Furthermore, the exon 3 mutation eliminated a BstEII restriction endonuclease site, allowing rapid identification of the change in genomic DNA. Surprisingly, only 23% of the M1 haplotypes were found to be BstEII site negative. The new form of M1, i.e., M1(ala213), is identical to M1 but has an isoelectric focusing 'silent' amino acid substitution. M1 has a frequency of 68 to 76%; M2, 14 to 20%; and M3, 10 to 12%. The Z gene represents 1 to 2% of all alpha-1-antitrypsin haplotypes. </p><p>Using 2 genomic probes extending into the 5-prime and 3-prime flanking regions, respectively, Cox et al. (1985) identified 8 polymorphic restriction sites for the PI gene. Extensive linkage disequilibrium was found with the PI Z allele throughout the probe region, but not with the normal PI M allele. The Z allele occurred mainly with one haplotype, indicating a single, relatively recent origin in Caucasians. This was an individual who lived in northern Europe some 6,000 years ago. Since then, the variant has spread through Europe with a frequency gradient extending from north to south: 5% of Scandinavians, 4% of Britons, 1 to 2% of southern Europeans, and 3% of the heterogeneous white population in the United States are MZ heterozygotes. Curiously, there is a reciprocal distribution of the S variant form: 10% in southern Europe to 5% in the north. As a general rule then, 1 in 10 persons of European origin will be heterozygous for either the S or Z variant, i.e., MZ or MS (Carrell, 1986). Kawakami et al. (1981) cited 2 studies in which no Pi Z was found among 965 healthy Japanese and 183 Japanese with pulmonary diseases. This is to be compared with a frequency of 1.6% for Pi Z among Norwegians. </p><p>Crystallographic analysis of alpha-1-antitrypsin predicts that in the normal protein a negatively charged glu342 is adjacent to a positively charged lys290. Thus, the glu342-to-lys Z mutation causes the loss of a normal salt bridge, resulting in intracellular aggregation of the Z molecule. Brantly et al. (1988) predicted that a second mutation that changed the positively charged lys290 to a negatively charged glu290 would correct the secretion defect. They demonstrated that such was the case: when the second mutation was added to the Z-type cDNA, the resulting gene directed the synthesis and secretion of AAT similar to that directed by the normal AAT cDNA in an in vitro eukaryotic expression system. In general it may be possible to correct human hereditary disease by inserting an additional mutation in the gene. </p><p>By analyzing nonrecombinant SNPs of 21 Latvian and 65 Swedish heterozygous and homozygous PI Z allele carriers and 113 healthy Latvian controls, Lace et al. (2008) estimated the age of the PI Z mutation to be 2,902 years in Latvia and 2,362 years in Sweden. The SNPs showed a high degree of similarity between the 2 populations, indicating a common ancestor. </p><p>Approximately 3 to 5% of patients with cystic fibrosis (CF; 219700) develop severe liver disease defined as cirrhosis with portal hypertension. Bartlett et al. (2009) performed a 2-stage case control study enrolling patients with CF and severe liver disease with portal hypertension from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America. In the first stage, 124 patients with CF and severe liver disease, enrolled between January 1999 and December 2004, and 843 control patients without CF-related liver disease (all assessed at greater than 15 years of age) were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the 2 genes that were positive from the first stage were tested in an additional 136 patients with CF-related liver disease enrolled between January 2005 and February 2007, and in 1,088 with no CF-related liver disease. The combined analysis of the initial and replication studies by logistic regression showed CF-related liver disease to be associated with the SERPINA1 Z allele (odds ratio = 5.04; 95% confidence interval 2.88-8.83; p = 1.5 x 10(-8)). Bartlett et al. (2009) concluded that the SERPINA1 Z allele is a risk factor for liver disease in CF. Patients carrying the Z allele are at greater risk (odds ratio = approximately 5) of developing severe liver disease with portal hypertension. </p><p>Using several markers of ER stress response, Kelly et al. (2009) found that expression of AAT with the Z mutation, which they called ZAAT, resulted in ER stress in transfected HepG2 cells. Coexpression of the ER stress response selenoprotein SEPS1 (607918) relieved ER stress caused by ZAAT expression or by exposure to tunicamycin, a known ER stressor. Supplementation of cells with selenium augmented the activity of SEPS1. Selenium supplementation also increased endogenous SEPS1 expression and reduced ER stress. </p><p>Using AT01 human liver cells overexpressing GP78, Khodayari et al. (2017) showed that GP78 (AMFR; 603243) regulated degradation of ubiquitinated ZAAT. GP78 targeted ZAAT for proteasomal degradation, and GP78 overexpression significantly decreased the level of accumulated ZAAT and caused faster ZAAT clearance from the ER, without significant changes in the level of extracellular ZAAT. This process involved VCP (601023), as GP78 interacted with VCP, and the interaction was enhanced in A1ATD liver tissue. SVIP (620965) expression was relatively high in A1ATD, and overexpression of SVIP negatively regulated GP78/VCP-mediated ERAD. Knockdown analysis in AT01 cells confirmed that endogenous SVIP negatively regulated GP78 function and inhibited ZAAT degradation. Electron microscopic analysis revealed that SVIP overexpression caused vacuole formation in AT01 cells, which was abrogated by silencing of SVIP. The authors proposed that GP78 overexpression or SVIP suppression may eliminate the toxic gain of function associated with ZAAT polymerization, thus providing a novel therapeutic approach to treatment of A1ATD. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 PI M(MALTON)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, PHE52DEL ON M2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs775982338,
|
|
|
|
|
|
gnomAD: rs775982338,
|
|
|
|
|
|
ClinVar: RCV000019568, RCV000019572, RCV000262058, RCV000594562, RCV003417992
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Liver disease, as well as emphysema, has been described in patients with the rare PI*M(Malton) allele. Fraizer et al. (1989) studied the molecular defect in M(Malton), a deficiency allele which, like the Z allele, is associated with hepatocyte inclusions and impairs secretion. They found that the M(Malton) allele contains a deletion of the codon for 1 of the 2 adjacent phenylalanine residues (amino acid 51 or 52 of the mature protein). Judging from the haplotype data, the M(Malton) mutation must have derived from the normal M2 allele. Deletion of the 1 amino acid would be expected to shorten 1 strand of the beta-sheet, B6, apparently preventing normal processing and secretion. Curiel et al. (1989) also showed that the M(Malton) allele differs from the normal M2 allele by deletion of the entire codon (TTC) for residue phe52. They demonstrated abnormal intracellular accumulation of newly synthesized AAT protein in a homozygote who also showed, on liver biopsy, inflammation, mild fibrosis, and intrahepatocyte accumulation of the protein. Furthermore, Curiel et al. (1989) showed by retroviral gene transfer of AAT cDNA with the M(Malton) phe52 deletion into murine cells that abnormal accumulation of the newly synthesized protein occurred. This provides further evidence that abnormal intrahepatocyte AAT accumulation is responsible for the liver injury. By means of gene amplification and direct DNA sequencing, Graham et al. (1989) identified the same mutation, pointing out that it could be either phenylalanine-51 or phenylalanine-52 that is deleted. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 PI S</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLU264VAL ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs17580,
|
|
|
|
|
|
gnomAD: rs17580,
|
|
|
|
|
|
ClinVar: RCV000019569, RCV000148878, RCV000177031, RCV000508742, RCV000508836, RCV000762932, RCV000768544, RCV000991136, RCV001195102, RCV002371777, RCV002466248, RCV003415722
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Owen and Carrell (1976) and Yoshida et al. (1977) found substitution of valine for glutamic acid at position 264 in the S variant of alpha-1-antitrypsin. See Long et al. (1984). </p><p>Curiel et al. (1989) concluded that the S-type AAT protein is degraded intracellularly before secretion. PI*S homozygotes are at no risk of emphysema, but compound heterozygotes with Z or a null allele have a mildly increased risk. Because of the high frequency of the PI*S allele (0.02-0.04 in US Caucasians), such compound heterozygotes are relatively frequent. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 PI M(HEERLEN)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, PRO369LEU ON M1A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422209,
|
|
|
|
|
|
gnomAD: rs199422209,
|
|
|
|
|
|
ClinVar: RCV000019565, RCV000409001, RCV000727230, RCV002336088, RCV003944831
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hofker et al. (1989) demonstrated the molecular defect in the PI gene of a patient with a serum level of only 5 mg/100 ml and a PI M-like phenotype, designated PI M(Heerlen). They demonstrated a substitution of leucine for proline at codon 369, which resulted from a C-to-T mutation in exon 5. Otherwise the nucleotide sequence of the exons, intron/exon junctions, and a part of the promoter region was similar to that of a PI M1(ala213) gene. Kalsheker et al. (1992) described a family with Pi M(Heerlen) and commented on the difficulties of diagnosis of rare PI (null) or Q0 variants. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 PI M(MINERAL SPRINGS)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLY67GLU ON M1A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931568,
|
|
|
|
|
|
|
|
ClinVar: RCV000019566, RCV000201855
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This mutation, which causes AAT deficiency and emphysema, is unique among antitrypsin mutations in that it was observed in a black family, whereas most mutations causing AAT deficiency are confined to Caucasian populations of European descent. The index case was homozygous. A GGG-to-GAG change in codon 67 led to substitution of glutamic acid for glycine (Curiel et al., 1990). Curiel et al. (1990) showed that this mutation caused reduced AAT secretion on the basis of aberrant posttranslational biosynthesis by a mechanism distinct from that associated with the Z allele, whereby intracellular aggregation of the mutant protein is responsible for the secretory defect. Furthermore, the M(Mineral Springs) mutation markedly affected the ability of the protein that did reach the circulation to inhibit neutrophil elastase. Homozygotes have a high risk of emphysema (Crystal, 1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 PI M(PROCIDA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, LEU41PRO ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931569,
|
|
|
|
|
|
gnomAD: rs28931569,
|
|
|
|
|
|
ClinVar: RCV000019571, RCV000201848, RCV000729804, RCV004584332
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Takahashi et al. (1988) showed that M(Procida) has a substitution of proline for leucine at position 41, resulting from a change of codon CTG to CCG. The rare mutant protein shows somewhat reduced catalytic activity; its concentration is low in plasma, apparently because of instability and resulting intracellular degradation before secretion. Homozygotes have a high risk of emphysema (Crystal, 1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 PI M(NICHINAN)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, PHE52DEL AND GLY148ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs112030253,
|
|
|
|
|
|
gnomAD: rs112030253,
|
|
|
|
|
|
ClinVar: RCV000019568, RCV000019572, RCV000262058, RCV000512621, RCV000594562, RCV000597384, RCV003417992
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Nakamura et al. (1980) found this variant in a 42-year-old Japanese woman with neither pulmonary emphysema nor liver dysfunction. She was the product of a consanguineous marriage. Radial immunodiffusion assay showed a low level of AAT in serum (17.9 mg/dl as compared to the normal range of 190-280 mg/dl). Aggregation of AAT molecules was demonstrated histologically in hepatocytes, indicating profound reduction in the secretion of the protein. Serum AAT levels in the members of the family demonstrated that the proband was homozygous for the M(Nichinan) allele. Matsunaga et al. (1990) demonstrated that the M(Nichinan) gene is identical with the M1(val213) gene except for 2 changes: a TTC trinucleotide deletion in the codon for phenylalanine-52 and a G-A substitution by which the normal gly148(GGG) became arg148(AGG). Matsunaga et al. (1990) suggested that the gly148-to-arg change is unlikely to be the cause of the AAT deficiency because arg (not gly) is located at the corresponding position of the protein C inhibitor which belongs to the same family of serine protease. On the other hand, Matsunaga et al. (1990) suggested that deletion of phenylalanine-52 may cause the newly synthesized AAT protein to aggregate, resulting in serum AAT deficiency. They suggested that the gly148-to-arg substitution reflects the vulnerability of a CpG dinucleotide to mutation. They pointed to a number of other variant forms of AAT that were probably generated through a C-T transition. Indeed, the Z and M1(val213) genes were generated from the M1(ala213) gene by the C-T transition at the CpG dinucleotide on the antisense and the sense strands, respectively. The M2 gene was generated from the M3 gene by the same mechanism. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 PI I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ARG39CYS ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931570,
|
|
|
|
|
|
gnomAD: rs28931570,
|
|
|
|
|
|
ClinVar: RCV000019575, RCV000148875, RCV000205893, RCV000431149, RCV003390693
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By gene amplification and direct DNA sequencing, Graham et al. (1989) identified this mutation, CGC to TGC, in a compound heterozygote. Homozygotes are at no risk of emphysema, but compound heterozygotes with Z or a null allele have a mildly increased risk (Crystal, 1989). In 1 individual and 3 independent families, Seri et al. (1992) confirmed that the I variant resulted from a CGC (arg)-to-TGC (cys) transition at codon 39 within exon 2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 PI P(LOWELL)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI NULL(CARDIFF)<br />
|
|
PI Q0(CARDIFF)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ASP256VAL ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912714,
|
|
|
|
|
|
gnomAD: rs121912714,
|
|
|
|
|
|
ClinVar: RCV000019576, RCV000019577, RCV000019578, RCV000019605, RCV000148876, RCV000398063, RCV003415723
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Faber et al. (1989) demonstrated that this rare allele, a cause of deficiency of alpha-1-antitrypsin, results from an A-to-T transversion in exon 3 of the gene. As a result, GAT (aspartic acid at residue 256) is converted to GTT (valine at that position). The same change was found in a total of 4 families. </p><p>By gene amplification and direct DNA sequencing, Graham et al. (1989) identified the same mutation in a variant they called Null(Cardiff). According to the tabulation by Crystal (1989), homozygotes have no risk for emphysema, but compound heterozygotes with a Z or null allele have a mildly increased risk. </p><p>By retroviral insertion of the P(Lowell) cDNA into the genome of NIH-3T3 fibroblasts, Holmes et al. (1990) demonstrated a pattern of biosynthesis of AAT consistent with the intracellular degradation of newly synthesized protein. Because serum AAT deficiency associated with other mutations resulting from intracellular degradation of the protein can be overcome by administration of estrogenlike drugs, Holmes et al. (1990) administered tamoxifen to a subject with the P(Lowell)/Z phenotype and demonstrated a 48% rise in AAT serum levels over a 5-month period, from below the threshold for protection from emphysema to a value above that threshold. Seri et al. (1992) confirmed the nature of the mutation in P(Lowell). </p><p>Hildesheim et al. (1993) demonstrated that P(Duarte) (107400.0037) has the same mutation as that in P(Lowell) but that it is on a background of the normal M4 allele (R101H; 107400.0005). Hildesheim et al. (1993) pointed out that this is an example of genetic diversity resulting from a limited repertoire of mutations on different common allelic backgrounds--a combinatorial basis for genetic diversity. A similar example is the occurrence of Creutzfeldt-Jakob disease and fatal familial insomnia as a result of the same mutation, depending on the nature of a nucleotide polymorphism at another site in the prion protein gene (PRNP; 176640.0010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 PI NULL(GRANITE FALLS)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(GRANITE FALLS)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, TYR160TER ON M1A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606950,
|
|
|
|
|
|
gnomAD: rs267606950,
|
|
|
|
|
|
ClinVar: RCV000019579, RCV000019580
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The gene shows deletion of the third nucleotide in the tyr160 codon TAC, causing a frameshift with new stop codon TAG at position 160 (Nukiwa et al., 1987). Emphysema is associated with homozygosity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 PI NULL(BELLINGHAM)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(BELLINGHAM)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, LYS217TER ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422211,
|
|
|
|
|
|
gnomAD: rs199422211,
|
|
|
|
|
|
ClinVar: RCV000019581, RCV000019582, RCV000169162, RCV001528835
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By cloning and sequencing the Null(Bellingham) gene (which in homozygous state is associated with early-onset emphysema), Satoh et al. (1988) demonstrated that the promoter region, coding exons, and all exon-intron junctions are normal except for a single base substitution in exon 3, which causes the normal lys217 (AAG) to become a stop codon (TAG). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 PI NULL(MATTAWA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, LEU353PHE ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28929473,
|
|
|
|
|
|
gnomAD: rs28929473,
|
|
|
|
|
|
ClinVar: RCV000019583
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Cox and Levison (1988) reported a family in which several members manifested no detectable plasma alpha-1-antitrypsin (613490), indicating a 'null' AAT allele, which the authors designated Null Mattawa (QO-Mattawa). Curiel et al. (1989) studied 2 affected sisters in this family and found that they were compound heterozygous for 2 mutations in the AAT gene: Null(Bellingham) (107400.0021) and Null(Mattawa). Sequencing of exons 1c-5 and all exon-intron junctions of the Null(Mattawa) gene demonstrated that it was identical to the common normal M1(val213) gene except for the insertion of a single nucleotide within the coding region of exon 5, causing a 3-prime frameshift with generation of a premature stop signal at position 376. Monocytes were shown to have an mRNA transcript of normal size, and in vitro translation showed that the mRNA was translated at a normal rate but produced a truncated antitrypsin protein. Additionally, retroviral transfer of the cDNA to murine fibroblasts demonstrated no detectable intracellular or secreted protein despite the presence of Null(Mattawa) mRNA. Thus, the molecular pathophysiology of Null(Mattawa) is probably manifested at a posttranslational level. This allele is associated with high risk of emphysema. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 PI NULL(PROCIDA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI NULL(ISOLA DI PROCIDA)<br />
|
|
PI Q0(PROCIDA)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, 17-KB DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019584, RCV000203601
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Of the 5 previously known representatives of the 'null' group of AAT-deficient alleles (i.e., genes incapable of producing AAT protein detectable in serum) evaluated at the gene level, all had stop codons in coding exons. Cloning and mapping of the Null(Isola di Procida) gene demonstrated deletion of a 17-kb fragment that included exons 2-5 of the AAT structural gene (Takahashi and Crystal, 1990). Sequence analysis showed a 7-bp repeat sequence both 5-prime to the deletion and at the 3-prime end of the deletion, suggesting that the mechanism of the deletion may have been a slipped mispairing. This mutation, which at first was called Null(Procida), was found in heterozygous state with the M(Procida) allele (107400.0016) reported by Takahashi et al. (1988). To avoid confusion with M(Procida), Null(Procida) was renamed Null(Isola di Procida). This mutation is associated with high risk of emphysema. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 PI NULL(HONG KONG 1)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(HONG KONG 1)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, 2-BP DEL, FS334TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057519610,
|
|
|
|
|
|
|
|
ClinVar: RCV000019587, RCV000019588, RCV000201857
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Deletion of TC from CTC codon 318 for leucine causes frameshift with stop codon TAA at position 334. Homozygosity for this allele, like other null alleles, predisposes to early-onset emphysema. See Sifers et al. (1988). This variant was initially called Null(Hong Kong) but later Null(Hong Kong-1) because a second null allele called Null(Hong Kong-2) (107400.0034) was identified in the same individual by haplotype analysis (Fraizer et al., 1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 PI NULL(BOLTON)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(BOLTON)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, 1-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs764325655,
|
|
|
|
|
|
gnomAD: rs764325655,
|
|
|
|
|
|
ClinVar: RCV000019589, RCV000019590, RCV000512620
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Fraizer et al. (1989) observed a unique PI null allele. By cloning and sequencing the allele, they demonstrated deletion of a single cytosine residue (the third C in the CCC codon 362 for proline) near the active site of alpha-1-antitrypsin in exon 5 resulting in a frameshift which caused an in-frame stop codon downstream of the deletion. The stop codon led to premature termination of protein translation at amino acid 373, resulting in a truncated protein. PI Q0(Bolton) was observed in combination with PI*M(Malton) in 2 compound heterozygotes. The allele carries a high risk of emphysema. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 PI PITTSBURGH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
'ANTITHROMBIN' PITTSBURGH
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, MET358ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912713,
|
|
|
|
|
|
gnomAD: rs121912713,
|
|
|
|
|
|
ClinVar: RCV000019591, RCV000201860
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This structure mutation in the PI gene alters its function such that it becomes an antithrombin and leads to a bleeding disorder. Alpha-1-antitrypsin and antithrombin III (107300) have a similar structure reflecting origin from a common ancestral protein some 500 million years ago. Both are inhibitors of proteolytic enzymes but have different specificities. Alpha-1-antitrypsin protects the body against released elastase, whereas AT III controls coagulation by inhibiting thrombin and other activated coagulation factors. Owen et al. (1983) described a mutation of alpha-1-antitrypsin that converts it to an antithrombin. Whereas synthesis of alpha-1-antitrypsin increases in response to trauma, AT III remains at a constant plasma concentration and requires activation by heparin. The antithrombin activity of the mutant alpha-1-antitrypsin was independent of heparin but its synthesis was stimulated by trauma. The patient was a 14-year-old boy who died in 1981 with a huge hematoma of his leg and abdomen. This was the last of a lifelong series of bleeding episodes occurring after trauma and requiring hospitalization on more than 50 occasions. Lewis et al. (1978) described the clinical picture and identified a variant 'antithrombin' which they called antithrombin Pittsburgh. It had, however, the electrophoretic and antigenic characteristics of a variant alpha-1-antitrypsin. Owen et al. (1983) showed that the variant protein has arginine at position 358, replacing the normal methionine. This finding indicated that the reactive center of alpha-1-antitrypsin is methionine 358, which acts as a 'bait' for elastase, just as the normal reactive center of AT III is arginine-393, which acts as a bait for thrombin. Neutrophils augment tissue proteolysis by the oxidative inactivation of the methionine at the reactive center of alpha-1-antitrypsin. Scott et al. (1986) and Schapira et al. (1986) found that recombinant AAT-Pittsburgh (met358-to-arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment, although it has lost its anti-elastase activity. They suggested it might have therapeutic potential in hereditary angioedema or septic shock. Vidaud et al. (1992) demonstrated that a G-to-T transversion at nucleotide 10038 is responsible for the substitution of arg for met, which converts alpha-1-antitrypsin into an arg-ser protease inhibitor (serpin) that inhibits thrombin and factor Xa more effectively than antithrombin III. They observed a 15-year-old boy who surprisingly had no bleeding history. They suggested that a large decrease in protein C concentration may account for the mild or absent bleeding tendency. The deficiency of protein C in turn was attributed to deleterious effect of the abnormal inhibitor on both intracellular processing and catabolism of protein C. In later studies, Emmerich et al. (1995) suggested that strong affinity of the mutant AAT for protein C leads in the patient of Vidaud et al. (1992) to an increased turnover and thus to a low circulating level of protein C. They proposed that in the presence of the Pittsburgh mutant protein C can be activated and is abnormally rapidly cleared. The resultant relative lack of protein C anticoagulant function may ameliorate the bleeding diathesis expected to be associated with the Pittsburgh mutation. </p><p>Wilkie (1994) discussed the molecular basis of genetic dominance and provided a useful table. He indicated altered substrate specificity as one mechanism and antithrombin Pittsburgh as a specific example. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 PI V(MUNICH)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ASP2ALA ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422212,
|
|
|
|
|
|
gnomAD: rs199422212,
|
|
|
|
|
|
ClinVar: RCV000019593, RCV000512626
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an alpha-1-antitrypsin variant called V(Munich) because the major fraction focused in the 'V' region of the isoelectric focusing gel, Holmes et al. (1990) found that the molecule differs from that of the common M1V allele by a single nucleotide substitution of cytosine for adenosine, with the resultant amino acid change asp2 to ala; the codon change is GAT to GCT. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 PI Z(AUGSBURG)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Z(TUN)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLU342LYS ON M2
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019567, RCV000019594, RCV000019595, RCV000148877, RCV000194811, RCV000255454, RCV000623762, RCV000768543, RCV001195107, RCV002054450, RCV002251912, RCV002276567, RCV002466247, RCV003415721
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Using isoelectric focusing with a narrow pH gradient, Weidinger et al. (1985) recognized a rare deficient PI variant, which they called PI Z(Augsburg). To their surprise, Faber et al. (1990) found that the sequence of the Z(Augsburg) gene showed the common PI*Z mutation (M1 glu342 GAG to Z lys342 AAG) which occurred, however, in an M2 ancestral gene. Previous findings indicated that the Z mutation had always been derived from an M1 ala213 background gene. Whitehouse et al. (1989) studied 2 sibs with mild liver abnormality who were found to be compound heterozygotes for the classical PI*Z allele and an allele that they called PI*Z(Tun). The Z(Tun) protein appeared to be deficient in the plasma to about the same degree as the Z protein. They found that the mutation was precisely the same as that in the Z allele, namely, a G-to-A transition at codon 342 resulting in the substitution of lysine for glutamic acid; however, the Z(Tun) mutation had occurred on an M2-like haplotype background rather than the M1A background. Because of its association with a unique DNA haplotype and the gene frequency estimates in populations of European origin, the Z mutation is thought to have occurred only once, about 6,000 years ago, in a North European person. The Z gene is very rare among other ethnic groups. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 PI W(BETHESDA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ALA336THR ON M1A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1802959,
|
|
|
|
|
|
gnomAD: rs1802959,
|
|
|
|
|
|
ClinVar: RCV000019596, RCV000512619, RCV000734987
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant allele, which is associated with increased risk of emphysema and liver disease, has a mutation in exon 5 where codon 336 is changed from GCT to ACT, resulting in substitution of threonine for alanine (Crystal, 1990). Holmes et al. (1990) reported that the W(Bethesda) form differs from the normal M1(ala-213) allele by a change in codon 336 from GCT to ACT. Although W(Bethesda) mRNA was translated normally in vitro, transfection of the W(Bethesda) cDNA into COS-I cells was associated with AAT secretion only 50% that of cells transfected with normal cDNA. There was no intracellular accumulation as observed with the Z allele, but reduced intracellular AAT suggested degradation of newly synthesized W(Bethesda) molecules. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 PI NULL(DEVON)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(DEVON)<br />
|
|
PI NULL(NEWPORT)<br />
|
|
PI Q0(NEWPORT)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, GLY115SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs11558261,
|
|
|
|
|
|
gnomAD: rs11558261,
|
|
|
|
|
|
ClinVar: RCV000019597, RCV000019598, RCV000019599, RCV000019600, RCV000512622
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, which is associated with increased risk of emphysema and liver disease, is due to a change in exon 2, resulting in substitution of serine for glycine-115 (Crystal, 1990). In a compound heterozygote carrying the common disease-producing mutation Pi Z (107400.0011), Graham et al. (1990) found a substitution of glycine-115 by serine. The mutation occurred on the background of M3. A change in codon 115 from GGC to AGC was responsible. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 PI NULL(LUDWIGSHAFEN)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(LUDWIGSHAFEN)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ILE92ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931572,
|
|
|
|
|
|
|
|
ClinVar: RCV000019601, RCV000019602, RCV000201851
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In this variant, which is associated with increased risk of emphysema and liver disease, a change in codon 92 from ATC to AAC in exon 2 results in substitution of asparagine for isoleucine (Crystal, 1990). This substitution of a polar for a nonpolar amino acid occurs in 1 of the alpha-helices and is predicted to disrupt the tertiary structure (Fraizer et al., 1990). Fraizer et al. (1990) identified a T-to-A substitution in a German patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 PI Z(WREXHAM)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, SER-19LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs140814100,
|
|
|
|
|
|
gnomAD: rs140814100,
|
|
|
|
|
|
ClinVar: RCV000019570, RCV000148880, RCV000596635
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a compound heterozygote with the common disease-producing PI Z mutation (107400.0011), Graham et al. (1990) found a change from TCG to TTG in codon -19, which resulted in a change from serine to leucine in the signal peptide. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0033 MOVED TO 107400.0028</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 PI NULL(HONG KONG 2)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(HONG KONG 2)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1,
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019573
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 107400.0024 and Fraizer et al. (1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 PI NULL(RIEDENBURG)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019603
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Poller et al. (1991) found complete deletion of the AAT gene as the basis for PI Q0(Riedenburg). The deletion extended into the 3-prime flanking region of the gene but did not include the noncoding AAT-related gene (PIL), which is located 12 kb downstream of AAT (Hofker et al., 1988). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 PI KALSHEKER-POLLER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, G-A, 3-PRIME UTR ENHANCER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs11568814,
|
|
|
|
|
|
gnomAD: rs11568814,
|
|
|
|
|
|
ClinVar: RCV000019604, RCV000333809, RCV004705301
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kalsheker et al. (1987) and Poller et al. (1990) reported a mutation in the 3-prime flanking sequence of the AAT gene that occurs in about 17% of patients with chronic respiratory disease. The mutation is a G-to-A nucleotide substitution in an octamer (OCT)-like sequence. Because TCGA is converted to TCAA, the mutation is detected as a restriction fragment length polymorphism with the restriction enzyme TaqI. The mutation does not appear to affect basal expression of the protein as the plasma concentration of alpha-1-antitrypsin is normal in persons who carry the mutation; however, binding and functional studies by Morgan et al. (1993) suggested that it may reduce the rise in plasma AAT concentration that occurs during inflammation. Stimulation by cytokines, such as interleukin-6 (IL6; 147620), may be lacking. Morgan et al. (1993) pointed out a precedent for such a mechanism in an unrelated gene: an enhancer element in the 3-prime flanking sequence of the erythropoietin gene increases gene expression nearly 15-fold during hypoxia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 PI P(DUARTE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, ASP256VAL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000019576, RCV000019577, RCV000019578, RCV000019605, RCV000148876, RCV000398063, RCV003415723
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hildesheim et al. (1993) demonstrated that the deficiency-producing change in the PI gene in P(Duarte) is the same as that in P(Lowell) (107400.0019). The alleles differ with respect to polymorphic nucleotides at other positions in the gene. They referred to this as genetic diversity from a limited repertoire of mutations on different common allelic backgrounds. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 PI NULL(WEST)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PI Q0(WEST)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, IVS2DS, G-T, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs751235320,
|
|
|
|
|
|
gnomAD: rs751235320,
|
|
|
|
|
|
ClinVar: RCV000019606, RCV000169461, RCV000593270
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>During routine screening of individuals applying for enrollment in the US AAT Deficiency Registry, Laubach et al. (1993) identified a patient with emphysema and a PI type heterozygous for a novel AAT null allele. The novel allele, designated PI*Q0(West), was characterized by a single G-to-T transversion at position 1 of intron 2, a highly conserved nucleotide position. This resulted in an in-frame deletion of amino acids gly164-to-lys191. This was the first splicing mutation observed in the AAT gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 PI S(IIYAMA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, SER53PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs55819880,
|
|
|
|
|
|
gnomAD: rs55819880,
|
|
|
|
|
|
ClinVar: RCV000019608, RCV000169508
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 32-year-old Japanese male with pulmonary emphysema, Yuasa et al. (1993) demonstrated homozygosity for a C-to-T transition at codon 53 resulting in substitution of phenylalanine for serine. They commented on the fact that, in Japanese, deficiency in null alleles at the AAT locus are extremely rare and PI*Z, which occurs at polymorphic frequencies in Caucasians, has not been reported. The only other Japanese case of AAT deficiency was that due to PI M(Nichinan) (107400.0017) reported by Matsunaga et al. (1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 PI Z(BRISTOL)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SERPINA1, THR85MET ON M1V
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199422213,
|
|
|
|
|
|
gnomAD: rs199422213,
|
|
|
|
|
|
ClinVar: RCV000019609, RCV000512618, RCV000731628
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with an obstetric history of 3 perinatal deaths from fulminant liver disease and no living offspring, Lovegrove et al. (1997) found that she and her father were both heterozygotes for PI M1Z(Bristol). The Z(Bristol) protein was found to be active as a proteinase inhibitor but appeared to be deficient in the plasma to about the same degree as the S protein in MS heterozygotes. It focused on the basic side of Z and lacked the normal pattern of secondary isoforms associated with the commonly occurring AAT variants and migrated faster than normal on an SDS electrophoresis gel. The Z(Bristol) mutation was found to be a C-to-T transition at codon 85, changing ACG (thr) to ATG (met). This disrupted the N-glycosylation site starting at asn83, preventing glycosylation at residue 83 in the PI Z(Bristol) protein, and explained the protein isoelectric focusing and SDS gel electrophoresis results. An analysis of haplotypes in the propositus and her father indicated that the Z(Bristol) mutation occurred on the common M1(val213) genetic background. Of the 3 offspring with perinatal death from fulminant liver disease, 2 were by the woman's husband and 1 by an artificial insemination donor. Of the 2 offspring who were tested for the mutation, 1 had the variant and the other did not. Thus, the relationship between Z(Bristol) and fulminant liver disease in the offspring was unclear. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Arnaud et al. (1978); Carrell et al. (1982); Chapuis-Cellier et al.
|
|
(1981); Cox and Smyth (1983); Cox (1975); Cox (1980); Cox (1981);
|
|
Faber et al. (1994); Faber et al. (1989); Fagerhol and Cox (1981);
|
|
Fagerhol and Gedde-Dahl (1969); Fagerhol and Hauge (1968); Fagerhol
|
|
and Laurell (1970); Fagerhol and Tenfjord (1968); Frants and Eriksson
|
|
(1980); Gedde-Dahl et al. (1975); Graham et al. (1990); Holmes et al.
|
|
(1990); Holmes et al. (1990); Hug et al. (1980); Iammarino et al.
|
|
(1979); Kramps et al. (1981); Kueppers and Christopherson (1978);
|
|
Lopez et al. (1964); Nukiwa et al. (1986); Owen et al. (1976);
|
|
Weitkamp et al. (1978); Welch et al. (1980); Yoshida et al. (1976);
|
|
Yoshida et al. (1979)
|
|
</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">
|
|
Arnaud, P., Galbraith, R. M., Galbraith, G. M. P., Allen, R. C., Fudenberg, H. H.
|
|
<strong>A new allele of human alpha-1-antitrypsin: Pi (N Hampton).</strong>
|
|
Am. J. Hum. Genet. 30: 653-659, 1978.
|
|
|
|
|
|
[PubMed: 311584]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Axelsson, U., Laurell, C. B.
|
|
<strong>Hereditary variants of serum alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 17: 466-472, 1965.
|
|
|
|
|
|
[PubMed: 4158556]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Babron, M. C., Constans, J., Dugoujon, J. M., Cambon-Thomsen, A., Bonaiti-Pellie, C.
|
|
<strong>The Gm-Pi linkage in 843 French families: effect of the alleles Pi Z and Pi S.</strong>
|
|
Ann. Hum. Genet. 54: 107-113, 1990.
|
|
|
|
|
|
[PubMed: 2382967]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1990.tb00366.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bartlett, J. R., Friedman, K. J., Ling, S. C., Pace, R. G., Bell, S. C., Bourke, B., Castaldo, G., Castellani, C., Cipolli, M., Colombo, C., Colombo, J. L., Debray, D., and 22 others.
|
|
<strong>Genetic modifiers of liver disease in cystic fibrosis.</strong>
|
|
JAMA 302: 1076-1083, 2009.
|
|
|
|
|
|
[PubMed: 19738092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.2009.1295]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bender, K., Muller, C. R., Schmidt, A., Strohmaier, U., Wienker, T. F.
|
|
<strong>Linkage studies on the human Pi, Gm, GLO, and HLA genes.</strong>
|
|
Hum. Genet. 49: 159-166, 1979.
|
|
|
|
|
|
[PubMed: 112033]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00277637]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Billingsley, G. D., Walter, M. A., Cox, D. W.
|
|
<strong>Physical linkage of alpha-1-antitrypsin and alpha-1-antichymotrypsin by pulsed field gel electrophoresis. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45 (suppl.): A130, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Billingsley, G. D., Walter, M. A., Hammond, G. L., Cox, D. W.
|
|
<strong>Physical mapping of four serpin genes: alpha-1-antitrypsin, alpha-1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome 14q32.1.</strong>
|
|
Am. J. Hum. Genet. 52: 343-353, 1993.
|
|
|
|
|
|
[PubMed: 8381582]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blanco, I., Bustillo, E. F., Rodriguez, M. C.
|
|
<strong>Distribution of alpha-1-antitrypsin PI S and PI Z frequencies in countries outside Europe: a meta-analysis.</strong>
|
|
Clin. Genet. 60: 431-441, 2001.
|
|
|
|
|
|
[PubMed: 11846735]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2001.600605.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boomsma, D. I., Frants, R. R., Bank, R. A., Martin, N. G.
|
|
<strong>Protease inhibitor (Pi) locus, fertility and twinning.</strong>
|
|
Hum. Genet. 89: 329-332, 1992.
|
|
|
|
|
|
[PubMed: 1601424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220552]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Botstein, D., White, R. L., Skolnick, M., Davis, R. W.
|
|
<strong>Construction of a genetic linkage map in man using restriction fragment length polymorphisms.</strong>
|
|
Am. J. Hum. Genet. 32: 314-331, 1980.
|
|
|
|
|
|
[PubMed: 6247908]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brantly, M., Courtney, M., Crystal, R. G.
|
|
<strong>Repair of the secretion defect in the Z form of alpha-1-antitrypsin by addition of a second mutation.</strong>
|
|
Science 242: 1700-1702, 1988.
|
|
|
|
|
|
[PubMed: 2904702]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.2904702]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brennan, S. O., Carrell, R. W.
|
|
<strong>Alpha-1-antitrypsin Christchurch, 363 glu-to-lys: mutation at the P-prime-5 position does not affect inhibitory activity.</strong>
|
|
Biochim. Biophys. Acta 873: 13-19, 1986.
|
|
|
|
|
|
[PubMed: 3527273]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0167-4838(86)90183-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bristow, C. L., Mercatante, D. R., Kole, R.
|
|
<strong>HIV-1 preferentially binds receptors copatched with cell-surface elastase.</strong>
|
|
Blood 102: 4479-4486, 2003.
|
|
|
|
|
|
[PubMed: 12933574]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2003-05-1635]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bristow, C. L., Patel, H., Arnold, R. R.
|
|
<strong>Self antigen prognostic for human immunodeficiency virus disease progression.</strong>
|
|
Clin. Diagn. Lab. Immun. 8: 937-942, 2001.
|
|
|
|
|
|
[PubMed: 11527807]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/CDLI.8.5.937-942.2001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bristow, C. L.
|
|
<strong>Slow human immunodeficiency virus (HIV) infectivity correlated with low HIV coreceptor levels.</strong>
|
|
Clin. Diagn. Lab. Immun. 8: 932-936, 2001.
|
|
|
|
|
|
[PubMed: 11527806]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/CDLI.8.5.932-936.2001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Campbell, R. A., Campbell, H. D., Bircher, J. S., de Araujo, C. V., Denorme, F., Crandell, J. L., Rustad, J. L., Monts, J., Cody, M. J., Kosaka, Y., Yost, C. C.
|
|
<strong>Placental HTRA1 cleaves alpha-1-antitrypsin to generate a NET-inhibitory peptide.</strong>
|
|
Blood 138: 977-988, 2021.
|
|
|
|
|
|
[PubMed: 34192300]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.2020009021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carrell, R. W., Jeppsson, J.-O., Laurell, C.-B., Brennan, S. O., Owen, M. C., Vaughan, L., Boswell, D. R.
|
|
<strong>Structure and variation of human alpha-1-antitrypsin.</strong>
|
|
Nature 298: 329-334, 1982.
|
|
|
|
|
|
[PubMed: 7045697]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/298329a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carrell, R. W.
|
|
<strong>Alpha-1-antitrypsin: molecular pathology, leukocytes, and tissue damage.</strong>
|
|
J. Clin. Invest. 78: 1427-1431, 1986.
|
|
|
|
|
|
[PubMed: 3537008]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112731]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chappell, S., Daly, L., Morgan, K., Baranes, T. G., Roca, J., Rabinovich, R., Millar, A., Donnelly, S. C., Keatings, V., MacNee, W., Stolk, J., Hiemstra, P., Miniati, M., Monti, S., O'Connor, C. M., Kalsheker, N.
|
|
<strong>Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease.</strong>
|
|
Hum. Mutat. 27: 103-109, 2006.
|
|
|
|
|
|
[PubMed: 16278826]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20275]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chapuis-Cellier, C., Verdier, M., Lepetit, J. C., Fudenberg, H. H., Arnaud, P.
|
|
<strong>Pi-Gm linkage: evidence for linkage in males but not in females and for an effect of the S allele of the Pi system.</strong>
|
|
J. Immunogenet. 8: 257-262, 1981.
|
|
|
|
|
|
[PubMed: 6792288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1744-313x.1981.tb00767.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clark, P., Breit, S. N., Dawkins, R. L., Penny, R.
|
|
<strong>Genetic study of a family with two members with Weber-Christian disease (panniculitis) and alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Med. Genet. 13: 57-62, 1982.
|
|
|
|
|
|
[PubMed: 6982619]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320130110]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clark, P., Martin, N. G.
|
|
<strong>An excess of the Pi(s) allele in dizygotic twins and their mothers.</strong>
|
|
Hum. Genet. 61: 171-174, 1982.
|
|
|
|
|
|
[PubMed: 6982218]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00274213]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Billingsley, G. D., Mansfield, T.
|
|
<strong>DNA restriction-site polymorphisms associated with the alpha-1-antitrypsin gene.</strong>
|
|
Am. J. Hum. Genet. 41: 891-906, 1987.
|
|
|
|
|
|
[PubMed: 2890296]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Levison, H.
|
|
<strong>Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes).</strong>
|
|
Am. Rev. Respir. Dis. 137: 371-375, 1988.
|
|
|
|
|
|
[PubMed: 3257661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1164/ajrccm/137.2.371]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Markovic, V. D., Teshima, I. E.
|
|
<strong>Genes for immunoglobulin heavy chains and for alpha-1-antitrypsin are localized to specific regions of chromosome 14q.</strong>
|
|
Nature 297: 428-430, 1982.
|
|
|
|
|
|
[PubMed: 6804874]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/297428a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Smyth, S.
|
|
<strong>Risk for liver disease in adults with alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Med. 74: 221-227, 1983.
|
|
|
|
|
|
[PubMed: 6600583]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(83)90615-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W., Woo, S. L. C., Mansfield, T.
|
|
<strong>DNA restriction fragments associated with alpha-1-antitrypsin indicate a single origin for deficiency allele PI Z.</strong>
|
|
Nature 316: 79-81, 1985.
|
|
|
|
|
|
[PubMed: 2989709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/316079a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>The effect of neuraminidase on genetic variants of alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 27: 165-177, 1975.
|
|
|
|
|
|
[PubMed: 1079112]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Genetic variation in alpha-1-antitrypsin. (Editorial)</strong>
|
|
Am. J. Hum. Genet. 30: 660-662, 1978.
|
|
|
|
|
|
[PubMed: 311585]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Transmission of Z allele from heterozygotes for alpha-1-antitrypsin deficiency. (Letter)</strong>
|
|
Am. J. Hum. Genet. 32: 455-457, 1980.
|
|
|
|
|
|
[PubMed: 17948551]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>New variants of alpha-1-antitrypsin: comparison of Pi typing techniques.</strong>
|
|
Am. J. Hum. Genet. 33: 354-365, 1981.
|
|
|
|
|
|
[PubMed: 6972696]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Alpha-1-antitrypsin deficiency. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic Basis of Inherited Disease. (6th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, D. W.
|
|
<strong>Alpha-1-antitrypsin. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. IV. (8th ed.)</strong>
|
|
New York: McGraw-Hill 2001. Pp. 5559-5584.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crystal, R. G.
|
|
<strong>The alpha-1-antitrypsin gene and its deficiency states.</strong>
|
|
Trends Genet. 5: 411-417, 1989.
|
|
|
|
|
|
[PubMed: 2696185]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0168-9525(89)90200-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin deficiency, emphysema, and liver disease: genetic basis and strategies for therapy.</strong>
|
|
J. Clin. Invest. 85: 1343-1352, 1990.
|
|
|
|
|
|
[PubMed: 2185272]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI114578]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Curiel, D., Brantly, M., Curiel, E., Stier, L., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin deficiency caused by the alpha-1-antitrypsin null(Mattawa) gene: an insertion mutation rendering the alpha-1-antitrypsin gene incapable of producing alpha-1-antitrypsin.</strong>
|
|
J. Clin. Invest. 83: 1144-1152, 1989. Note: Erratum: J. Clin. Invest. 84: following 1041, 1989.
|
|
|
|
|
|
[PubMed: 2539391]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI113994]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Curiel, D. T., Chytil, A., Courtney, M., Crystal, R. G.
|
|
<strong>Serum alpha-1-antitrypsin deficiency associated with the common S-type (glu264-to-val) mutation results from intracellular degradation of alpha-1-antitrypsin prior to secretion.</strong>
|
|
J. Biol. Chem. 264: 10477-10486, 1989.
|
|
|
|
|
|
[PubMed: 2567291]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Curiel, D. T., Holmes, M. D., Okayama, H., Brantly, M. L., Vogelmeier, C., Travis, W. D.
|
|
<strong>Stier, L. E.; Perks, W. H. and Crystal, R. G.: Molecular basis of the liver and lung disease associated with the alpha-1-antitrypsin deficiency allele M(Malton).</strong>
|
|
J. Biol. Chem. 264: 13938-13945, 1989.
|
|
|
|
|
|
[PubMed: 2788166]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Curiel, D. T., Vogelmeier, C., Hubbard, R. C., Stier, L. E., Crystal, R. G.
|
|
<strong>Molecular basis of alpha-1-antitrypsin deficiency and emphysema associated with the alpha-1-antitrypsin M(Mineral Springs) allele.</strong>
|
|
Molec. Cell. Biol. 10: 47-56, 1990.
|
|
|
|
|
|
[PubMed: 1967187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.10.1.47-56.1990]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Darlington, G. J., Astrin, K. H., Muirhead, S. P., Desnick, R. J., Smith, M.
|
|
<strong>Assignment of human alpha-1-antitrypsin to chromosome 14 by somatic cell hybrid analysis.</strong>
|
|
Proc. Nat. Acad. Sci. 79: 870-873, 1982.
|
|
|
|
|
|
[PubMed: 6801664]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.79.3.870]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
DeCroo, S., Kamboh, M. I., Ferrell, R. E.
|
|
<strong>Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.</strong>
|
|
Hum. Hered. 41: 215-221, 1991.
|
|
|
|
|
|
[PubMed: 1783408]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000154004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dycaico, M. J., Grant, S. G. N., Felts, K., Nichols, W. S., Geller, S. A., Hager, J. H., Pollard, A. J., Kohler, S. W., Short, H. P., Jirik, F. R., Hanahan, D., Sorge, J. A.
|
|
<strong>Neonatal hepatitis induced by alpha-1-antitrypsin: a transgenic mouse model.</strong>
|
|
Science 242: 1409-1415, 1988.
|
|
|
|
|
|
[PubMed: 3264419]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3264419]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Emmerich, J., Alhenc-Gelas, M., Gandrille, S., Guichet, C., Fiessinger, J.-N., Aiach, M.
|
|
<strong>Mechanism of protein C deficiency in a patient with arginine 358 alpha(1)-antitrypsin (Pittsburgh mutation): role in the maintenance of hemostatic balance.</strong>
|
|
J. Lab. Clin. Med. 125: 531-539, 1995.
|
|
|
|
|
|
[PubMed: 7706910]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faber, J. P., Poller, W., Weidinger, S., Kirchgesser, M., Schwaab, R., Bidlingmaier, S., Olek, K.
|
|
<strong>Identification and DNA sequence analysis of 15 new alpha-1-antitrypsin variants, including two Pi* Q alleles and one deficient Pi* M allele.</strong>
|
|
Am. J. Hum. Genet. 55: 1113-1121, 1994.
|
|
|
|
|
|
[PubMed: 7977369]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faber, J. P., Weidinger, S., Goedde, H.-W., Olek, K.
|
|
<strong>The deficient alpha-1-antitrypsin phenotype Pi P is associated with an A-to-T transversion in exon III of the gene. (Letter)</strong>
|
|
Am. J. Hum. Genet. 45: 161-163, 1989.
|
|
|
|
|
|
[PubMed: 2787118]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faber, J. P., Weidinger, S., Olek, K.
|
|
<strong>Sequence data of two rare deficient alpha-1-antitrypsin phenotypes. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 995-996, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faber, J.-P., Weidinger, S., Olek, K.
|
|
<strong>Sequence data of the rare deficient alpha-1-antitrypsin variant PI Z(Augsburg).</strong>
|
|
Am. J. Hum. Genet. 46: 1158-1162, 1990.
|
|
|
|
|
|
[PubMed: 2339709]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Braend, M.
|
|
<strong>Serum prealbumin: polymorphism in man.</strong>
|
|
Science 149: 986-987, 1965.
|
|
|
|
|
|
[PubMed: 5827347]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.149.3687.986]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Cox, D. W.
|
|
<strong>The Pi polymorphism: genetic, biochemical, and clinical aspects of human alpha-1-antitrypsin.</strong>
|
|
Adv. Hum. Genet. 11: 1-62, 1981.
|
|
|
|
|
|
[PubMed: 6168185]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Gedde-Dahl, T., Jr.
|
|
<strong>Genetics of the Pi serum types: family studies of the inherited variants of serum alpha-1-antitrypsin.</strong>
|
|
Hum. Hered. 19: 354-359, 1969.
|
|
|
|
|
|
[PubMed: 5366282]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000152238]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Hauge, H. E.
|
|
<strong>The Pi phenotype MP: discovery of a ninth allele belonging to the system of inherited variants of serum alpha-1-antitrypsin.</strong>
|
|
Vox Sang. 15: 396-400, 1968.
|
|
|
|
|
|
[PubMed: 5699691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1423-0410.1968.tb04081.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Laurell, C. B.
|
|
<strong>The polymorphism of 'prealbumins' and alpha-1-antitrypsin in human sera.</strong>
|
|
Clin. Chim. Acta 16: 199-203, 1967.
|
|
|
|
|
|
[PubMed: 4166396]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0009-8981(67)90181-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Laurell, C. B.
|
|
<strong>The Pi system--inherited variants of serum alpha-1-antitrypsin.</strong>
|
|
Prog. Med. Genet. 7: 96-111, 1970.
|
|
|
|
|
|
[PubMed: 4911922]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K., Tenfjord, O. W.
|
|
<strong>Serum Pi types in some European, American, Asian and African populations.</strong>
|
|
Acta Path. Microbiol. Scand. 72: 601-608, 1968.
|
|
|
|
|
|
[PubMed: 5681806]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1699-0463.1968.tb00472.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerhol, M. K.
|
|
<strong>The Pi system: genetic variants of serum alpha-1-antitrypsin.</strong>
|
|
Ser. Haemat. 1: 153-161, 1968.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fraizer, G. C., Harrold, T. R., Hofker, M. H., Cox, D. W.
|
|
<strong>In-frame single codon deletion in the M(Malton) deficiency allele of alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 44: 894-902, 1989.
|
|
|
|
|
|
[PubMed: 2786335]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fraizer, G. C., Siewertsen, M. A., Hofker, M. H., Brubacher, M. G., Cox, D. W.
|
|
<strong>A null deficiency allele of alpha-1-antitrypsin, Q0-Ludwigshafen, with altered tertiary structure.</strong>
|
|
J. Clin. Invest. 86: 1878-1884, 1990.
|
|
|
|
|
|
[PubMed: 2254451]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI114919]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fraizer, G. C., Siewertsen, M., Harold, T. R., Cox, D. W.
|
|
<strong>Deletion/frameshift mutation in the alpha-1-antitrypsin null allele, PI*Q0(Bolton).</strong>
|
|
Hum. Genet. 83: 377-382, 1989.
|
|
|
|
|
|
[PubMed: 2807278]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00291385]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frants, R., Eriksson, A. W.
|
|
<strong>A new unstable Pi M variant of alpha-1-antitrypsin in a Finnish isolate.</strong>
|
|
Hum. Hered. 30: 333-342, 1980.
|
|
|
|
|
|
[PubMed: 6971248]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000153154]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garver, R. I., Jr., Mornex, J.-F., Nukiwa, T., Brantly, M., Courtney, M., LeCocq, J.-P., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin deficiency and emphysema caused by homozygous inheritance of non-expressing alpha-1-antitrypsin genes.</strong>
|
|
New Eng. J. Med. 314: 762-766, 1986.
|
|
|
|
|
|
[PubMed: 3485249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198603203141207]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Cook, P. J. L., Fagerhol, M. K., Pierce, J. A.
|
|
<strong>Improved estimate of the Gm-Pi linkage.</strong>
|
|
Ann. Hum. Genet. 39: 43-50, 1975.
|
|
|
|
|
|
[PubMed: 810069]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1975.tb00106.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Cook, P. J. L., Fagerhol, M. K., Pierce, J. A.
|
|
<strong>The Gm-Pi linkage: a summary estimate.</strong>
|
|
Birth Defects Orig. Art. Ser. XI(3): 157-158, 1975. Note: Alternate: Cytogenet. Cell Genet. 14: 327-328, 1975.
|
|
|
|
|
|
[PubMed: 54196]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Fagerhol, M. K., Cook, P. J. L., Noades, J.
|
|
<strong>Autosomal linkage between the Gm and Pi loci in man.</strong>
|
|
Ann. Hum. Genet. 35: 393-400, 1972.
|
|
|
|
|
|
[PubMed: 5073686]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Frants, R., Olaisen, B., Eriksson, A. W., van Loghem, E., Lamm, L.
|
|
<strong>The Gm-Pi linkage heterogeneity in view of Pi M subtypes.</strong>
|
|
Ann. Hum. Genet. 45: 143-153, 1981.
|
|
|
|
|
|
[PubMed: 6797346]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1981.tb00316.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Graham, A., Hayes, K., Weidinger, S., Newton, C. R., Markham, A. F., Kalsheker, N. A.
|
|
<strong>Characterisation of the alpha-1-antitrypsin M3 gene, a normal variant.</strong>
|
|
Hum. Genet. 85: 381-382, 1990.
|
|
|
|
|
|
[PubMed: 2394452]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00206766]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Graham, A., Kalsheker, N. A., Bamforth, F. J., Newton, C. R., Markham, A. F.
|
|
<strong>Molecular characterization of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) null(Newport) (gly(115)-to-ser) and (Pi) Z Wrexham (ser(-19)-to-leu).</strong>
|
|
Hum. Genet. 85: 537-540, 1990.
|
|
|
|
|
|
[PubMed: 2227940]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00194233]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Graham, A., Kalsheker, N. A., Newton, C. R., Bamforth, F. J., Powell, S. J., Markham, A. F.
|
|
<strong>Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null (Cardiff) (asp256-to-val), Pi M(Malton) (phe51-deletion) and Pi I (arg39-to-cys).</strong>
|
|
Hum. Genet. 84: 55-58, 1989.
|
|
|
|
|
|
[PubMed: 2606478]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00210671]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, C., Brown, G., Dafforn, T. R., Reichhart, J.-M., Morley, T., Lomas, D. A., Gubb, D.
|
|
<strong>Drosophila necrotic mutations mirror disease-associated variants of human serpins.</strong>
|
|
Development 130: 1473-1478, 2003.
|
|
|
|
|
|
[PubMed: 12588861]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1242/dev.00350]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hafeez, W., Ciliberto, G., Perlmutter, D. H.
|
|
<strong>Constitutive and modulated expression of the human alpha-1 antitrypsin gene: different transcriptional initiation sites used in three different cell types.</strong>
|
|
J. Clin. Invest. 89: 1214-1222, 1992.
|
|
|
|
|
|
[PubMed: 1556183]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115705]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hidvegi, T., Ewing, M., Hale, P., Dippold, C., Beckett, C., Kemp, C., Maurice, N., Mukherjee, A., Goldbach, C., Watkins, S., Michalopoulos, G., Perlmutter, D. H.
|
|
<strong>An autophagy-enhancing drug promotes degradation of mutant alpha-1-antitrypsin Z and reduces hepatic fibrosis.</strong>
|
|
Science 329: 229-232, 2010.
|
|
|
|
|
|
[PubMed: 20522742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1190354]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hildesheim, J., Kinsley, G., Bissell, M., Pierce, J., Brantly, M.
|
|
<strong>Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha-1-antitrypsin deficiency variant P(Duarte).</strong>
|
|
Hum. Mutat. 2: 221-228, 1993.
|
|
|
|
|
|
[PubMed: 8364590]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380020311]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hofker, M. H., Nelen, M., Klasen, E. C., Nukiwa, T., Curiel, D., Crystal, R. G., Frants, R. R.
|
|
<strong>Cloning and characterization of an alpha-1-antitrypsin like gene 12 kb downstream of the genuine alpha-1-antitrypsin gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 155: 634-642, 1988.
|
|
|
|
|
|
[PubMed: 2901833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0006-291x(88)80542-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hofker, M. H., Nukiwa, T., van Paassen, H. M. B., Nelen, M., Kramps, J. A., Klasen, E. C., Frants, R. R., Crystal, R. G.
|
|
<strong>A pro-to-leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen.</strong>
|
|
Hum. Genet. 81: 264-268, 1989.
|
|
|
|
|
|
[PubMed: 2784123]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00279001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmes, M. D., Brantly, M. L., Crystal, R. G.
|
|
<strong>Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.</strong>
|
|
Am. Rev. Resp. Dis. 142: 1185-1192, 1990.
|
|
|
|
|
|
[PubMed: 2240842]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1164/ajrccm/142.5.1185]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmes, M. D., Brantly, M. L., Curiel, D. T., Weidinger, S., Crystal, R. G.
|
|
<strong>Characterization of the normal alpha-1-antitrypsin allele V(Munich): a variant associated with a unique protein isoelectric focusing pattern.</strong>
|
|
Am. J. Hum. Genet. 46: 810-816, 1990.
|
|
|
|
|
|
[PubMed: 2316526]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmes, M. D., Brantly, M. L., Fells, G. A., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin W(Bethesda): molecular basis of an unusual alpha-1-antitrypsin deficiency variant.</strong>
|
|
Biochem. Biophys. Res. Commun. 170: 1013-1020, 1990.
|
|
|
|
|
|
[PubMed: 2390072]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(90)90493-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hug, G., Chuck, G., Fagerhol, M. K.
|
|
<strong>Pi(P-Clifton): a new alpha(1) antitrypsin allele in an American Negro family.</strong>
|
|
J. Med. Genet. 18: 43-45, 1981.
|
|
|
|
|
|
[PubMed: 6973024]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.18.1.43]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hug, G., Chuck, G., Slemmer, T. M., Fagerhol, M. K.
|
|
<strong>Pi (Ecincinnati): a new alpha-1-antitrypsin allele in three Negro families.</strong>
|
|
Hum. Genet. 54: 361-364, 1980.
|
|
|
|
|
|
[PubMed: 6967446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00291583]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hutchison, D. C. S.
|
|
<strong>Alpha-1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z.</strong>
|
|
Respir. Med. 92: 367-377, 1998.
|
|
|
|
|
|
[PubMed: 9692092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0954-6111(98)90278-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iammarino, R. M., Wagener, D. K., Allen, R. C.
|
|
<strong>Segregation distortion of the alpha-1-antitrypsin Pi Z allele.</strong>
|
|
Am. J. Hum. Genet. 31: 508-517, 1979.
|
|
|
|
|
|
[PubMed: 314754]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kalsheker, N. A., Hodgson, I. J., Watkins, G. L., White, J. P., Morrison, H. M., Stockley, R. A.
|
|
<strong>Deoxyribonucleic acid (DNA) polymorphism of the alpha-1-antitrypsin gene in chronic lung disease.</strong>
|
|
Brit. Med. J. 294: 1511-1514, 1987.
|
|
|
|
|
|
[PubMed: 3038256]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.294.6586.1511]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kalsheker, N., Hayes, K., Weidinger, S., Graham, A.
|
|
<strong>What is Pi (proteinase inhibitor) null or PiQ0? A problem highlighted by the alpha-1-antitrypsin M(Heerlen) mutation.</strong>
|
|
J. Med. Genet. 29: 27-29, 1992.
|
|
|
|
|
|
[PubMed: 1552539]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.29.1.27]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kamimoto, T., Shoji, S., Hidvegi, T., Mizushima, N., Umebayashi, K., Perlmutter, D. H., Yoshimori, T.
|
|
<strong>Intracellular inclusions containing mutant alpha(1)-antitrypsin Z are propagated in the absence of autophagic activity.</strong>
|
|
J. Biol. Chem. 281: 4467-4476, 2006.
|
|
|
|
|
|
[PubMed: 16365039]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M509409200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawakami, Y., Irie, T., Kishi, F., Asanuma, Y., Shida, A., Yoshikawa, T., Kamishima, K., Hasegawa, H., Murao, M.
|
|
<strong>Familial aggregation of abnormal ventilatory control and pulmonary function in chronic obstructive pulmonary disease.</strong>
|
|
Europ. J. Resp. Dis. 62: 56-64, 1981.
|
|
|
|
|
|
[PubMed: 7227484]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kelly, E., Greene, C. M., Carroll, T. P., McElvaney, N. G., O'Neill, S. J.
|
|
<strong>Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha-1-antitrypsin deficiency.</strong>
|
|
J. Biol. Chem. 284: 16891-16897, 2009.
|
|
|
|
|
|
[PubMed: 19398551]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M109.006288]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keyeux, G., Gilgenkrantz, S., Lefranc, G., Lefranc, M.-P.
|
|
<strong>Molecular characterization of a ring chromosome 14 showing that the PI locus is centromeric to the D14S1 and IGH loci.</strong>
|
|
Hum. Genet. 82: 219-222, 1989.
|
|
|
|
|
|
[PubMed: 2543620]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00291158]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Khodayari, N., Wang, R. L., Marek, G., Krotova, K., Kirst, M., Liu, C., Rouhani, F., Brantly, M.
|
|
<strong>SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78.</strong>
|
|
PLoS One 12: e0172983, 2017.
|
|
|
|
|
|
[PubMed: 28301499]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.pone.0172983]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kramps, J. A., Brouwers, J. W., Maesen, F., Dijkman, J. H.
|
|
<strong>Pi(M-Heerlen), a Pi(M) allele resulting in very low alpha-1-antitrypsin serum levels.</strong>
|
|
Hum. Genet. 59: 104-107, 1981.
|
|
|
|
|
|
[PubMed: 6976926]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00293055]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kueppers, F., Bearn, A. G.
|
|
<strong>An inherited alpha-1-antitrypsin variant.</strong>
|
|
Humangenetik 4: 217-220, 1967.
|
|
|
|
|
|
[PubMed: 6080804]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00292195]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kueppers, F., Christopherson, M. J.
|
|
<strong>Alpha-1-antitrypsin: further genetic heterogeneity revealed by isoelectric focusing.</strong>
|
|
Am. J. Hum. Genet. 30: 359-365, 1978.
|
|
|
|
|
|
[PubMed: 309724]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kurachi, K., Chandra, T., Degen, S. J. F., White, T. T., Marchioro, T. L., Woo, S. L. C., Davie, E. W.
|
|
<strong>Cloning and sequence of cDNA coding for alpha-1-antitrypsin.</strong>
|
|
Proc. Nat. Acad. Sci. 78: 6826-6830, 1981.
|
|
|
|
|
|
[PubMed: 7031661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.78.11.6826]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lace, B., Sveger, T., Krams, A., Cernevska, G., Krumina, A.
|
|
<strong>Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis.</strong>
|
|
Ann. Hum. Genet. 72: 300-304, 2008.
|
|
|
|
|
|
[PubMed: 18294358]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.2008.00431.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lai, E. C., Kao, F.-T., Law, M. L., Woo, S. L. C.
|
|
<strong>Assignment of the alpha-1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization.</strong>
|
|
Am. J. Hum. Genet. 35: 385-392, 1983.
|
|
|
|
|
|
[PubMed: 6602546]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laubach, V. E., Ryan, W. J., Brantly, M.
|
|
<strong>Characterization of a human alpha-1-antitrypsin null allele involving aberrant mRNA splicing.</strong>
|
|
Hum. Molec. Genet. 2: 1001-1005, 1993.
|
|
|
|
|
|
[PubMed: 8364536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.7.1001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledbetter, S. A., Ledbetter, D. H., Ledley, F. D., Woo, S.
|
|
<strong>Localization of phenylalanine hydroxylase (PAH) and alpha-1 antitrypsin (AAT) loci in mouse genome by synteny and in situ hybridization. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 41: A173, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lewis, J. H., Iammarino, R. M., Spero, J. A., Hasiba, U.
|
|
<strong>Antithrombin Pittsburgh: an alpha-1-antitrypsin variant causing hemorrhagic disease.</strong>
|
|
Blood 51: 129-137, 1978.
|
|
|
|
|
|
[PubMed: 412531]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lieberman, J., Borhani, N. O., Feinleib, M.
|
|
<strong>Alpha-1-antitrypsin deficiency in twins and parents-of-twins.</strong>
|
|
Clin. Genet. 15: 29-36, 1979.
|
|
|
|
|
|
[PubMed: 310370]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1979.tb02026.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W., Kurachi, K.
|
|
<strong>Complete sequence of the cDNA for human alpha-1-antitrypsin and the gene for the S variant.</strong>
|
|
Biochemistry 23: 4828-4837, 1984.
|
|
|
|
|
|
[PubMed: 6093867]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00316a003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lopez, V., Oetliker, O., Colombo, J. P., Butler, R.
|
|
<strong>Ein Fall von familiaerem alpha-1-Antitrypsinmangel.</strong>
|
|
Helv. Paediat. Acta 19: 296-303, 1964.
|
|
|
|
|
|
[PubMed: 14229909]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lovegrove, J. U., Jeremiah, S., Gillett, G. T., Temple, I. K., Povey, S., Whitehouse, D. B.
|
|
<strong>A new alpha 1-antitrypsin mutation, thr-met 85, (PI Z-Bristol) associated with novel electrophoresis properties.</strong>
|
|
Ann. Hum. Genet. 61: 385-391, 1997.
|
|
|
|
|
|
[PubMed: 9459000]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1469-1809.1997.6150385.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martorana, P. A., Brand, T., Gardi, C., van Even, P., de Santi, M. M., Calzoni, P., Marcolongo, P., Lungarella, G.
|
|
<strong>The pallid mouse: a model of genetic alpha-1-antitrypsin deficiency.</strong>
|
|
Lab. Invest. 68: 233-241, 1993.
|
|
|
|
|
|
[PubMed: 8441253]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsunaga, E., Shiokawa, S., Nakamura, H., Maruyama, T., Tsuda, K., Fukumaki, Y.
|
|
<strong>Molecular analysis of the gene of the alpha-1-antitrypsin deficiency variant, M(Nichinan).</strong>
|
|
Am. J. Hum. Genet. 46: 602-612, 1990.
|
|
|
|
|
|
[PubMed: 2309708]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morgan, K., Scobie, G., Kalsheker, N. A.
|
|
<strong>Point mutation in a 3-prime flanking sequence of the alpha-1-antitrypsin gene associated with chronic respiratory disease occurs in a regulatory sequence.</strong>
|
|
Hum. Molec. Genet. 2: 253-257, 1993.
|
|
|
|
|
|
[PubMed: 8499914]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.3.253]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Munch, J., Standker, L., Adermann, K., Schulz, A., Schindler, M., Chinnadurai, R., Pohlmann, S., Chaipan, C., Biet, T., Peters, T., Meyer, B., Wilhelm, D., Lu, H., Jing, W., Jiang, S., Forssmann, W.-G., Kirchhoff, F.
|
|
<strong>Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide.</strong>
|
|
Cell 129: 263-275, 2007.
|
|
|
|
|
|
[PubMed: 17448989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2007.02.042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakamura, H., Ogawa, A., Hisano, S., Fukuma, M., Tachibana, N., Tsuda, K.
|
|
<strong>A family with a new deficient variant of alpha-1-antitrypsin PiM(Nichinan): with special reference to diastase-resistant, periodic acid-Schiff positive globules in the liver cells.</strong>
|
|
J. Jpn. Soc. Intern. Med. 69: 47-54, 1980.
|
|
|
|
|
|
[PubMed: 6162902]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2169/naika.69.967]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Brantly, M., Garver, R., Paul, L., Courtney, M., LeCocq, J.-P., Crystal, R. G.
|
|
<strong>Evaluation of 'at risk' alpha-1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes.</strong>
|
|
J. Clin. Invest. 77: 528-537, 1986.
|
|
|
|
|
|
[PubMed: 3484754]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112333]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Brantly, M. L., Ogushi, F., Fells, G. A., Crystal, R. G.
|
|
<strong>Characterization of the gene and protein of the common alpha-1-antitrypsin normal M2 allele.</strong>
|
|
Am. J. Hum. Genet. 43: 322-330, 1988.
|
|
|
|
|
|
[PubMed: 2901226]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Satoh, K., Brantly, M. L., Ogushi, F., Fells, G. A., Courtney, M., Crystal, R. G.
|
|
<strong>Identification of a second mutation in the protein-coding sequence of the Z type alpha-1-antitrypsin gene.</strong>
|
|
J. Biol. Chem. 261: 15989-15994, 1986. Note: Erratum: J. Biol. Chem. 262: 10412 only, 1987.
|
|
|
|
|
|
[PubMed: 3491072]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nukiwa, T., Takahashi, H., Brantly, M., Courtney, M., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin null (Granite Falls), a nonexpressing alpha-1-antitrypsin gene associated with a frameshift to stop mutation in a coding exon.</strong>
|
|
J. Biol. Chem. 262: 11999-12004, 1987.
|
|
|
|
|
|
[PubMed: 3040726]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okayama, H., Brantly, M., Holmes, M., Crystal, R. G.
|
|
<strong>Characterization of the molecular basis of the alpha-1-antitrypsin F allele.</strong>
|
|
Am. J. Hum. Genet. 48: 1154-1158, 1991.
|
|
|
|
|
|
[PubMed: 2035534]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Owen, M. C., Brennan, S. O., Lewis, J. H., Carrell, R. W.
|
|
<strong>Mutation of antitrypsin to antithrombin: alpha-1-antitrypsin Pittsburgh (358 met-to-arg), a fatal bleeding disorder.</strong>
|
|
New Eng. J. Med. 309: 694-698, 1983.
|
|
|
|
|
|
[PubMed: 6604220]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198309223091203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Owen, M. C., Carrell, R. W., Brennan, S. O.
|
|
<strong>The abnormality of the S variant of human alpha-1-antitrypsin.</strong>
|
|
Biochim. Biophys. Acta 453: 257-261, 1976.
|
|
|
|
|
|
[PubMed: 1087161]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0005-2795(76)90271-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Owen, M. C., Carrell, R. W.
|
|
<strong>Alpha-1-antitrypsin: molecular abnormality of S variant.</strong>
|
|
Brit. Med. J. 1: 130-131, 1976.
|
|
|
|
|
|
[PubMed: 1082356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.1.6002.130-a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pearson, S., Tetri, P., George, D. L., Francke, U.
|
|
<strong>Alpha-1-antitrypsin (PI) expression in rat hepatoma-human somatic cell hybrids: evidence for PI locus on chromosome 14 and for regulatory locus on the X chromosome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 33: 148A, 1981.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Perlino, E., Cortese, R., Ciliberto, G.
|
|
<strong>The human alpha-1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes.</strong>
|
|
EMBO J. 6: 2767-2771, 1987.
|
|
|
|
|
|
[PubMed: 3500042]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1987.tb02571.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poller, W., Faber, J.-P., Weidinger, S., Olek, K.
|
|
<strong>DNA polymorphisms associated with a new alpha-1-antitrypsin PI Q0 variant (PI Q0-Riedenburg).</strong>
|
|
Hum. Genet. 86: 522-524, 1991.
|
|
|
|
|
|
[PubMed: 1673114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00194647]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poller, W., Meisen, C., Olek, K.
|
|
<strong>DNA polymorphisms of the alpha-1-antitrypsin gene region in patients with chronic obstructive pulmonary disease.</strong>
|
|
Europ. J. Clin. Invest. 20: 1-7, 1990.
|
|
|
|
|
|
[PubMed: 1969347]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2362.1990.tb01769.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roychoudhury, A. K., Nei, M.
|
|
<strong>Human Polymorphic Genes: World Distribution.</strong>
|
|
New York: Oxford Univ. Press (pub.) 1988. Pp. 132-135.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Satoh, K., Nukiwa, T., Brantly, M., Garver, R. I., Jr., Hofker, M., Courtney, M., Crystal, R. G.
|
|
<strong>Emphysema associated with complete absence of alpha-1-antitrypsin in serum and the homozygous inheritance of a stop codon in an alpha-1-antitrypsin-coding exon.</strong>
|
|
Am. J. Hum. Genet. 42: 77-83, 1988. Note: Erratum: Am. J. Hum. Genet. 42: 789 only, 1988.
|
|
|
|
|
|
[PubMed: 3257351]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schapira, M., Ramus, M.-A., Jallat, S., Carvallo, D., Courtney, M.
|
|
<strong>Recombinant alpha-1-antitrypsin Pittsburgh (met-358 to arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment.</strong>
|
|
J. Clin. Invest. 77: 635-637, 1986.
|
|
|
|
|
|
[PubMed: 3484756]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schroeder, W. T., Miller, M. F., Woo, S. L. C., Saunders, G. F.
|
|
<strong>Chromosomal localization of the human alpha-antitrypsin gene (PI) to 14q31-32.</strong>
|
|
Am. J. Hum. Genet. 37: 868-872, 1985.
|
|
|
|
|
|
[PubMed: 3876766]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, C. F., Carrell, R. W., Glaser, C. B., Kueppers, F., Lewis, J. H., Colman, R. W.
|
|
<strong>Alpha-1-antitrypsin-Pittsburgh: a potent inhibitor of human plasma factor XIa, kallikrein, and factor XII.</strong>
|
|
J. Clin. Invest. 77: 631-634, 1986.
|
|
|
|
|
|
[PubMed: 3484755]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112346]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sefton, L., Kearney, P., Kelsey, G., Povey, S., Wolfe, J.
|
|
<strong>Physical linkage of the genes PI and AACT. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1076, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seixas, S., Mendonca, C., Costa, F., Rocha, J.
|
|
<strong>Alpha-1-antitrypsin null alleles: evidence for the recurrence of the L353fsX376 mutation and a novel G-to-A transition in position +1 of intron IC affecting normal mRNA splicing.</strong>
|
|
Clin. Genet. 62: 175-180, 2002.
|
|
|
|
|
|
[PubMed: 12220457]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620212.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seri, M., Magi, B., Cellesi, C., Olia, P. M., Renieri, A., De Marchi, M.
|
|
<strong>Molecular characterization of the P and I variants of alpha-1-antitrypsin.</strong>
|
|
Int. J. Clin. Lab. Res. 22: 119-121, 1992.
|
|
|
|
|
|
[PubMed: 1504305]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF02591409]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shapiro, L., Pott, G. B., Ralston, A. H.
|
|
<strong>Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1.</strong>
|
|
FASEB J. 15: 115-122, 2001.
|
|
|
|
|
|
[PubMed: 11149899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1096/fj.00-0311com]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sifers, R. N., Brashears-Macatee, S., Kidd, V. J., Muensch, H., Woo, S. L. C.
|
|
<strong>A frameshift mutation results in a truncated alpha-1-antitrypsin that is retained within the rough endoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 263: 7330-7335, 1988.
|
|
|
|
|
|
[PubMed: 3259232]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soutoglou, E., Talianidis, I.
|
|
<strong>Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation.</strong>
|
|
Science 295: 1901-1904, 2002.
|
|
|
|
|
|
[PubMed: 11884757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1068356]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takahashi, H., Crystal, R. G.
|
|
<strong>Alpha-1-antitrypsin Null(Isola di Procida): an alpha-1-antitrypsin deficiency allele caused by deletion of all alpha-1-antitrypsin coding exons.</strong>
|
|
Am. J. Hum. Genet. 47: 403-413, 1990.
|
|
|
|
|
|
[PubMed: 1975477]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takahashi, H., Nukiwa, T., Satoh, K., Ogushi, F., Brantly, M., Fells, G., Stier, L., Courtney, M., Crystal, R. G.
|
|
<strong>Characterization of the gene and protein of the alpha-1-antitrypsin 'deficiency' allele M(procida).</strong>
|
|
J. Biol. Chem. 263: 15528-15534, 1988.
|
|
|
|
|
|
[PubMed: 3262617]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M., Arthuis, M., Jeanson, C.
|
|
<strong>Two patients with interstitial del(14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin).</strong>
|
|
Ann. Genet. 27: 237-240, 1984.
|
|
|
|
|
|
[PubMed: 6335371]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van Pel, M., van Os, R., Velders, G. A., Hagoort, H., Heegaard, P. M. H., Lindley, I. J. D., Willemze, R., Fibbe, W. E.
|
|
<strong>Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 1469-1474, 2006.
|
|
|
|
|
|
[PubMed: 16432201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0510192103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Emmerich, J., Alhenc-Gelas, M., Yvart, J., Fiessinger, J. N., Aiach, M.
|
|
<strong>Met358-to-arg mutation of alpha-1-antitrypsin associated with protein C deficiency in a patient with mild bleeding tendency.</strong>
|
|
J. Clin. Invest. 89: 1537-1543, 1992.
|
|
|
|
|
|
[PubMed: 1569192]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115746]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weidinger, S., Jahn, W., Cujnik, F., Schwarzfischer, F.
|
|
<strong>Alpha-1-antitrypsin: evidence for a fifth PI M subtype and a new deficiency allele PI*Z(Augsburg).</strong>
|
|
Hum. Genet. 71: 27-29, 1985.
|
|
|
|
|
|
[PubMed: 3875547]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00295662]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weitkamp, L. R., Cox, D., Guttormsen, S., Johnston, E., Hempfling, S.
|
|
<strong>Allelic specific heterogeneity in the Pi-Gm linkage group.</strong>
|
|
Cytogenet. Cell Genet. 22: 647-650, 1978.
|
|
|
|
|
|
[PubMed: 313312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000131044]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Welch, S. G., McGregor, I. A., Williams, K.
|
|
<strong>Alpha-1-antitrypsin (Pi) phenotypes in a village population from the Gambia, West Africa.</strong>
|
|
Hum. Genet. 53: 233-235, 1980.
|
|
|
|
|
|
[PubMed: 6965658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00273503]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whitehouse, D. B., Abbott, C. M., Lovegrove, J. U., McIntosh, I., McMahon, C. J., Mieli-Vergani, G., Mowat, A. P., Hopkinson, D. A.
|
|
<strong>Genetic studies on a new deficiency gene (PI*Z-Tun) at the PI locus.</strong>
|
|
J. Med. Genet. 26: 744-749, 1989.
|
|
|
|
|
|
[PubMed: 2575668]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.26.12.744]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M.
|
|
<strong>The molecular basis of genetic dominance.</strong>
|
|
J. Med. Genet. 31: 89-98, 1994.
|
|
|
|
|
|
[PubMed: 8182727]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.31.2.89]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamamoto, Y., Sawa, R., Okamoto, N., Matsui, A., Yanagisawa, M., Ikemoto, S.
|
|
<strong>Deletion 14q(q24.3 to q32.1) syndrome: significance of peculiar facial appearance in its diagnosis, and deletion mapping of Pi (alpha-1-antitrypsin).</strong>
|
|
Hum. Genet. 74: 190-192, 1986.
|
|
|
|
|
|
[PubMed: 3490426]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00282092]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Chillar, R., Taylor, J. C.
|
|
<strong>An alpha-1-antitrypsin variant, PiB Alhambra (lys-to-asp, glu-to-asp), with rapid anodal electrophoretic mobility.</strong>
|
|
Am. J. Hum. Genet. 31: 555-563, 1979.
|
|
|
|
|
|
[PubMed: 315708]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Ewing, C., Wessels, M., Lieberman, J., Gaidulis, L.
|
|
<strong>Molecular abnormality of Pi S variant of human alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 29: 233-239, 1977.
|
|
|
|
|
|
[PubMed: 301355]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Lieberman, J., Gaidulis, L., Ewing, C.
|
|
<strong>Molecular abnormality of human alpha-1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency.</strong>
|
|
Proc. Nat. Acad. Sci. 73: 1324-1328, 1976.
|
|
|
|
|
|
[PubMed: 1083527]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.73.4.1324]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshida, A., Taylor, J. C., Van den Brock, W. G. M.
|
|
<strong>Structural difference between the normal PiM(1) and the common PiM(2) variant of human alpha-1-antitrypsin.</strong>
|
|
Am. J. Hum. Genet. 31: 564-568, 1979.
|
|
|
|
|
|
[PubMed: 315709]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yuasa, I., Sugimoto, Y., Ichinose, M., Matsumoto, Y., Fukumaki, Y., Sasaki, T., Okada, K.
|
|
<strong>PI*S(Iiyama), a deficiency gene of alpha-1-antitrypsin: evidence for the occurrence in western Japan.</strong>
|
|
Jpn. J. Hum. Genet. 38: 185-191, 1993.
|
|
|
|
|
|
[PubMed: 8358043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01883709]
|
|
|
|
|
|
</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">
|
|
Bao Lige - updated : 11/06/2024<br>Bao Lige - updated : 08/31/2022<br>Patricia A. Hartz - updated : 7/11/2012<br>Ada Hamosh - updated : 9/7/2011<br>Ada Hamosh - updated : 8/17/2010<br>Cassandra L. Kniffin - updated : 1/13/2009<br>Paul J. Converse - updated : 8/17/2007<br>Paul J. Converse - updated : 3/24/2006<br>Victor A. McKusick - updated : 1/20/2006<br>Paul J. Converse - updated : 3/14/2005<br>Victor A. McKusick - updated : 12/4/2003<br>Victor A. McKusick - updated : 7/10/2003<br>Ada Hamosh - updated : 4/15/2003<br>Victor A. McKusick - updated : 11/26/2002<br>Victor A. McKusick - updated : 6/3/2002<br>Ada Hamosh - updated : 4/2/2002<br>Victor A. McKusick - updated : 2/12/2002<br>Victor A. McKusick - updated : 1/10/2002<br>Victor A. McKusick - updated : 10/21/1999<br>Victor A. McKusick - updated : 12/10/1998<br>Victor A. McKusick - updated : 11/5/1998<br>Victor A. McKusick - updated : 7/10/1998<br>Cynthia K. Ewing - updated : 10/23/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 11/06/2024<br>carol : 09/30/2022<br>mgross : 08/31/2022<br>carol : 07/20/2016<br>carol : 07/18/2016<br>carol : 7/15/2016<br>carol : 7/14/2016<br>carol : 7/9/2016<br>carol : 7/9/2016<br>alopez : 8/7/2013<br>carol : 5/21/2013<br>terry : 4/4/2013<br>terry : 3/15/2013<br>carol : 8/15/2012<br>terry : 8/8/2012<br>terry : 7/11/2012<br>carol : 5/30/2012<br>terry : 10/10/2011<br>mgross : 10/3/2011<br>alopez : 9/8/2011<br>terry : 9/7/2011<br>terry : 9/7/2010<br>terry : 9/7/2010<br>terry : 9/7/2010<br>alopez : 8/18/2010<br>joanna : 8/17/2010<br>terry : 8/17/2010<br>carol : 8/13/2010<br>carol : 9/15/2009<br>terry : 6/3/2009<br>wwang : 4/1/2009<br>wwang : 1/16/2009<br>ckniffin : 1/13/2009<br>terry : 1/8/2009<br>terry : 1/8/2009<br>terry : 1/7/2009<br>terry : 1/7/2009<br>carol : 10/4/2007<br>mgross : 8/17/2007<br>mgross : 3/29/2006<br>terry : 3/24/2006<br>carol : 2/14/2006<br>alopez : 1/25/2006<br>terry : 1/20/2006<br>carol : 11/28/2005<br>mgross : 3/14/2005<br>mgross : 3/14/2005<br>mgross : 3/17/2004<br>alopez : 12/10/2003<br>terry : 12/4/2003<br>carol : 11/24/2003<br>carol : 7/21/2003<br>terry : 7/10/2003<br>alopez : 4/17/2003<br>terry : 4/15/2003<br>cwells : 11/26/2002<br>terry : 11/20/2002<br>cwells : 6/26/2002<br>terry : 6/3/2002<br>carol : 4/25/2002<br>alopez : 4/5/2002<br>terry : 4/2/2002<br>terry : 3/13/2002<br>terry : 2/12/2002<br>cwells : 1/25/2002<br>cwells : 1/16/2002<br>terry : 1/10/2002<br>alopez : 11/23/1999<br>carol : 10/21/1999<br>carol : 12/16/1998<br>terry : 12/10/1998<br>carol : 11/16/1998<br>terry : 11/5/1998<br>dkim : 7/24/1998<br>dkim : 7/24/1998<br>carol : 7/15/1998<br>terry : 7/10/1998<br>terry : 5/29/1998<br>terry : 1/29/1998<br>mark : 10/14/1997<br>mark : 10/14/1997<br>dholmes : 8/14/1997<br>alopez : 7/31/1997<br>jenny : 7/9/1997<br>joanna : 7/3/1997<br>joanna : 6/24/1997<br>terry : 1/10/1997<br>mark : 12/29/1996<br>jamie : 10/23/1996<br>jamie : 10/16/1996<br>jamie : 10/14/1996<br>mark : 3/25/1996<br>terry : 7/10/1995<br>mark : 6/13/1995<br>pfoster : 5/2/1995<br>davew : 8/18/1994<br>jason : 6/17/1994<br>warfield : 4/4/1994
|
|
</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>
|
|
|
|
|