6664 lines
619 KiB
Text
6664 lines
619 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- #613490 - ALPHA-1-ANTITRYPSIN DEFICIENCY; A1ATD
|
|
|
|
|
|
- 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=613490"><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">#613490</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/613490"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#otherFeatures">Other Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#diagnosis">Diagnosis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalManagement">Clinical Management</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular 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="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=ALPHA-1-ANTITRYPSIN DEFICIENCY" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
|
|
<div id="mimEuroGentestFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=18024&Typ=Pat" title="Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hemorrhagic disease due to… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=194&Typ=Pat" title="Alpha-1-antitrypsin deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Alpha-1-antitrypsin defici… </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1519/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/325" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/condition/alpha-1-antitrypsin-deficiency" 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=613490[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
|
|
<div id="mimOrphanetFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178396" title="Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hemorrhagic disease due to…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=60" title="Alpha-1-antitrypsin deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Alpha-1-antitrypsin defici…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:13372" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/disease/613490" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/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://wormbase.org/resources/disease/DOID:13372" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 30188007<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> E88.01<br />
|
|
|
|
|
|
<strong>ICD9CM:</strong> 273.4<br />
|
|
|
|
|
|
<strong>ORPHA:</strong> 178396, 60<br />
|
|
|
|
|
|
<strong>DO:</strong> 13372<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
613490
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ALPHA-1-ANTITRYPSIN DEFICIENCY; A1ATD
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/492?start=-3&limit=10&highlight=492">
|
|
14q32.13
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<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>
|
|
<td>
|
|
<span class="mim-font">
|
|
SERPINA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107400"> 107400 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<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>
|
|
<td>
|
|
<span class="mim-font">
|
|
SERPINA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107400"> 107400 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<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">
|
|
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>
|
|
<td>
|
|
<span class="mim-font">
|
|
SERPINA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107400"> 107400 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/613490" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/613490" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613490" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Dyspnea (onset 35 years in smokers, 45 years in nonsmokers) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808343&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808343</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267036007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267036007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230145002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230145002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.02</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/786.05" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.05</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002094" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002094</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Airways </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Small airways <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862763&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862763</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Lung </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Alveolar wall destruction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862764</a>]</span><br /> -
|
|
Emphysema especially at bases <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862765&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862765</a>]</span><br /> -
|
|
Chronic obstructive pulmonary disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13645005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13645005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J44.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J44.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024117&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024117</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006510</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Abnormal liver function tests <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166603001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166603001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R94.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R94.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/794.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">794.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151766&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151766</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br /> -
|
|
Hepatic intracellular inclusions in ZZ homozygotes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862758</a>]</span><br /> -
|
|
Infantile liver abnormalities in <20% with deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862759&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862759</a>]</span><br /> -
|
|
Cirrhosis (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19943007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19943007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023890&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023890</a>, <a href="https://bioportal.bioontology.org/search?q=C1623038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1623038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased hepatocellular carcinoma risk <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862761&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862761</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Serum alpha-1-antitrypsin (Pi) deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808342&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808342</a>]</span><br /> -
|
|
Abnormal liver function tests (SGOT, SGPT) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862756</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166603001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166603001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R94.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R94.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/794.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">794.8</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Z allele most common, only in Caucasians<br /> -
|
|
Secondary prevention, avoid smoking, alcohol, and oxidants<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the protease inhibitor 1 gene (PI, <a href="/entry/107400#0001">107400.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because alpha-1-antitrypsin deficiency (A1ATD) is caused by mutation in the SERPINA1 gene (<a href="/entry/107400">107400</a>), most often by homozygosity for the PiZ allele (<a href="/entry/107400#0011">107400.0011</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Alpha-1-antitrypsin deficiency (A1ATD) is an autosomal recessive disorder. The most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age (<a href="#20" 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="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="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#66" class="mim-tip-reference" title="Laurell, C.-B., Eriksson, S. <strong>The electrophoretic alpha-1-globulin pattern of serum in alpha-1-antitrypsin deficiency.</strong> Scand. J. Clin. Lab. Invest. 15: 132-140, 1963."None>Laurell and Eriksson (1963)</a> described absence of alpha-1-antitrypsin from the plasma in patients with degenerative lung disease leading to death in middle life. Emphysematous changes involve primarily the lower lung fields (<a href="#7" class="mim-tip-reference" title="Bell, R. S. <strong>The radiographic manifestations of alpha-1 antitrypsin deficiency: an important recognizable pattern of chronic obstructive pulmonary disease (COPD).</strong> Radiology 95: 19-24, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5417042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5417042</a>] [<a href="https://doi.org/10.1148/95.1.19" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5417042">Bell, 1970</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5417042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Gans, H., Sharp, H. L., Tan, B. H. <strong>Antiprotease deficiency and familial infantile liver cirrhosis.</strong> Surg. Gynec. Obstet. 129: 289-299, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4240153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4240153</a>]" pmid="4240153">Gans et al. (1969)</a> described familial infantile liver cirrhosis in presumed homozygotes for alpha-1-antitrypsin deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4240153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>An adult with antitrypsin deficiency and combined liver and lung disease was reported by <a href="#42" class="mim-tip-reference" title="Gherardi, G. J. <strong>Alpha-1-antitrypsin deficiency and its effect on the liver.</strong> Hum. Path. 2: 173-175, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5095241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5095241</a>] [<a href="https://doi.org/10.1016/s0046-8177(71)80026-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5095241">Gherardi (1971)</a>. See the study of 12 cases of combined disease by <a href="#8" class="mim-tip-reference" title="Berg, N. O., Eriksson, S. <strong>Liver disease in adults with alpha-1-antitrypsin deficiency.</strong> New Eng. J. Med. 287: 1264-1267, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117996</a>] [<a href="https://doi.org/10.1056/NEJM197212212872502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4117996">Berg and Eriksson (1972)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5095241+4117996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Aagenaes, O., Matlary, A., Elgjo, K., Munthe, E., Fagerhol, M. <strong>Neonatal cholestasis in alpha-1-antitrypsin deficient children: clinical, genetic, histological and immunohistochemical findings.</strong> Acta Paediat. Scand. 61: 632-642, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117022</a>] [<a href="https://doi.org/10.1111/j.1651-2227.1972.tb15960.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4117022">Aagenaes et al. (1972)</a> described the clinical picture in children with severe AAT deficiency (ZZ genotype) as neonatal cholestasis. Five such cases were described. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4117022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Fargion, S., Klasen, E. C., Lalatta, F., Sangalli, G., Tommasini, M., Fiorelli, G. <strong>Alpha-1-antitrypsin in patients with carcinoma and chronic active hepatitis.</strong> Clin. Genet. 19: 134-139, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6258829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6258829</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1981.tb00684.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6258829">Fargion et al. (1981)</a> found an increased frequency of non-M phenotypes in patients with hepatocellular carcinoma. Furthermore, patients with liver cancer and a non-M phenotype had a lower average age than those with an M phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6258829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="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://doi.org/10.1016/0002-9343(83)90615-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6600583">Cox and Smyth (1983)</a> found a relatively high risk for liver disease in men between 51 and 60 years who had AAT deficiency. A low concentration of serum prealbumin was a sensitive indicator of impaired liver function. <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'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Eriksson, S., Carlson, J., Velez, R. <strong>Risk of cirrhosis and primary liver cancer in alpha-1-antitrypsin deficiency.</strong> New Eng. J. Med. 314: 736-739, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485248</a>] [<a href="https://doi.org/10.1056/NEJM198603203141202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3485248">Eriksson et al. (1986)</a> concluded that the risk of cirrhosis and liver cancer is increased for males homozygous for alpha-1-antitrypsin deficiency but not for females. The finding suggested additive effects of exogenous factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Wiebicke, W., Niggemann, B., Fischer, A. <strong>Pulmonary function in children with homozygous alpha-1-protease inhibitor deficiency.</strong> Europ. J. Pediat. 155: 603-607, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8831086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8831086</a>] [<a href="https://doi.org/10.1007/BF01957913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8831086">Wiebicke et al. (1996)</a> confirmed the absence of pulmonary function abnormalities in the vast majority of children with severe (homozygous ZZ) AAT deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8831086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#88" class="mim-tip-reference" title="Rodriguez-Cintron, W., Guntupalli, K., Fraire, A. E. <strong>Bronchiectasis and homozygous (PiZZ) alpha1-antitrypsin deficiency in a young man.</strong> Thorax 50: 424-425, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7785020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7785020</a>] [<a href="https://doi.org/10.1136/thx.50.4.424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7785020">Rodriguez-Cintron et al. (1995)</a> suggested that bronchiectasis should be considered part of the spectrum of pulmonary pathology that may be encountered in individuals with AAT deficiency. They described a 21-year-old man with massive hemoptysis and severe (homozygous ZZ) AAT deficiency. Neither panlobular emphysema nor cirrhosis of the liver was present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7785020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="otherFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimOtherFeaturesFold" id="mimOtherFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimOtherFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimOtherFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#78" class="mim-tip-reference" title="Morin, T., Martin, J.-P., Feldmann, G., Rueff, B., Benhamou, J.-P., Ropartz, C. <strong>Heterozygous alpha (1)-antitrypsin deficiency and cirrhosis in adults, a fortuitous association.</strong> Lancet 305: 250-251, 1975. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/46389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">46389</a>] [<a href="https://doi.org/10.1016/s0140-6736(75)91143-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="46389">Morin et al. (1975)</a> concluded that heterozygotes are not at increased risk of alcoholic cirrhosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=46389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Geddes, D. M., Webley, M., Brewerton, D. A., Turton, C. W., Turner-Warwick, M., Murphy, A. H., Ward, A. M. <strong>Alpha-1-antitrypsin phenotypes in fibrosing alveolitis and rheumatoid arthritis.</strong> Lancet 310: 1049-1051, 1977. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/72955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">72955</a>] [<a href="https://doi.org/10.1016/s0140-6736(77)91883-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="72955">Geddes et al. (1977)</a> found that the frequency of non-M AAT phenotypes was increased to a significant extent in patients with sclerosing alveolitis with or without rheumatoid arthritis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=72955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="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><a href="#48" class="mim-tip-reference" title="Hendrick, S. J., Silverman, A. K., Solomon, A. R., Headington, J. T. <strong>Alpha-1-antitrypsin deficiency associated with panniculitis.</strong> J. Am. Acad. Derm. 18: 684-692, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259592</a>] [<a href="https://doi.org/10.1016/s0190-9622(88)70091-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3259592">Hendrick et al. (1988)</a> described 3 patients in whom panniculitis was the presenting manifestation of AAT deficiency. Two were young adults and 1 was a child. The panniculitis in these cases is frequently, although not always, precipitated by trauma. The panniculitis is chronic, relapsing, and widely disseminated with new lesions appearing as old lesions resolve. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3259592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Fortin, P. R., Fraser, R. S., Watts, C. S., Esdaile, J. M. <strong>Alpha-1 antitrypsin deficiency and systemic necrotizing vasculitis.</strong> J. Rheum. 18: 1613-1616, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1684994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1684994</a>]" pmid="1684994">Fortin et al. (1991)</a> reported a third incidence of systemic vasculitis associated with the ZZ genotype, which took the form of polyarteritis nodosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1684994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="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="#15" 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 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. No fertility indices other than twinning itself were available. To study relationships between Pi types, fertility, and twinning, <a href="#10" 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=1601424+310370+6982218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="diagnosis" class="mim-anchor"></a>
|
|
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#59" class="mim-tip-reference" title="Kidd, V. J., Wallace, R. B., Itakura, K., Woo, S. L. C. <strong>Alpha-1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.</strong> Nature 304: 230-234, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6306478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6306478</a>] [<a href="https://doi.org/10.1038/304230a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6306478">Kidd et al. (1983)</a> used a chemically synthesized specific oligonucleotide probe (19-mer) as a sensitive and direct test for the presence or absence of the Z allele (E342K; <a href="/entry/107400#0011">107400.0011</a>). <a href="#58" class="mim-tip-reference" title="Kidd, V. J., Golbus, M. S., Wallace, R. B., Itakura, K., Woo, S. L. C. <strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency by direct analysis of the mutation site in the gene.</strong> New Eng. J. Med. 310: 639-642, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6607413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6607413</a>] [<a href="https://doi.org/10.1056/NEJM198403083101007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6607413">Kidd et al. (1984)</a> reported the use of such probes in the prenatal diagnosis of the deficiency syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6607413+6306478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#47" class="mim-tip-reference" title="Hejtmancik, J. F., Sifers, R. N., Ward, P. A., Harris, S., Mansfield, T., Cox, D. W. <strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency by restriction fragment length polymorphisms, and comparison with oligonucleotide probe analysis.</strong> Lancet 328: 767-769, 1986. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2876232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2876232</a>] [<a href="https://doi.org/10.1016/s0140-6736(86)90297-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2876232">Hejtmancik et al. (1986)</a> compared prenatal diagnosis by RFLP analysis with prenatal diagnosis by oligonucleotide probe analysis. They concluded that although it seems reasonable to use oligonucleotide analysis in families in which no sibs are available for comparison, in all other situations RFLP analysis is preferable because it is as accurate and reliable as oligonucleotide analysis and is technically easier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2876232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Abbott, C. M., McMahon, C. J., Whitehouse, D. B., Povey, S. <strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency using polymerase chain reaction. (Letter)</strong> Lancet 331: 763-764, 1988. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2895285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2895285</a>] [<a href="https://doi.org/10.1016/s0140-6736(88)91565-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2895285">Abbott et al. (1988)</a> used the PCR for prenatal diagnosis of alpha-1-antitrypsin deficiency associated with the ZZ genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2895285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>To identify accurately the SZ phenotype at the DNA level, <a href="#81" 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> prepared 19-mer synthetic oligonucleotide probes: 2 to show the M/S difference in exon 3, and 2 to show the M/Z difference in exon 5. <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'})"><span class="glyphicon 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="#46" class="mim-tip-reference" title="Harrison, H. H., Miller, K. L., Whitington, P. F. <strong>Improved detection, via ISO-DALT two-dimensional electrophoresis, of 'low Z expressor' individuals with alpha-1-antitrypsin MZ phenotype.</strong> Clin. Chem. 36: 1850-1851, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2208671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2208671</a>]" pmid="2208671">Harrison et al. (1990)</a> described an improved method for detecting what they termed 'low Z expressor' phenotype in MZ heterozygotes. An obligate carrier mother who was being typed as part of a family study appeared to be a PI(M)/PI(null) heterozygote. By routine isoelectric focusing, she was typed as M, her affected child as Z, and her husband as MZ. Atypically low concentrations of circulating Z peptides were demonstrated by the improved method. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2208671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#26" class="mim-tip-reference" title="Dry, P. J. <strong>Rapid detection of alpha-1-antitrypsin deficiency by analysis of a PCR-induced TaqI restriction site.</strong> Hum. Genet. 87: 742-744, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1937480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1937480</a>] [<a href="https://doi.org/10.1007/BF00201739" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1937480">Dry (1991)</a> described a method for detecting the single-base substitution in PiZ useful for same-day diagnosis of AAT deficiency in chorion villus samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1937480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#105" class="mim-tip-reference" title="Udall, J. N., Bloch, K. J., Walker, W. A. <strong>Transport of proteases across neonatal intestine and development of liver disease in infants with alpha-1-antitrypsin deficiency.</strong> Lancet 319: 1441-1443, 1982. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6123724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6123724</a>] [<a href="https://doi.org/10.1016/s0140-6736(82)92454-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6123724">Udall et al. (1982)</a> speculated that a factor in the pathogenesis of infantile cirrhosis may be lack of protease inhibitor to counteract the effects of proteases that cross the intestinal barrier in the neonate. <a href="#64" class="mim-tip-reference" title="Lake-Bakaar, G., Dooley, J. S. <strong>Alpha-1-antitrypsin deficiency and liver disease. (Letter)</strong> Lancet 320: 159 only, 1982. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6123870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6123870</a>] [<a href="https://doi.org/10.1016/s0140-6736(82)91127-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6123870">Lake-Bakaar and Dooley (1982)</a> found that alpha-1-antitrypsin is an important proteolytic inhibitor in bile, thus providing support of the pathogenetic theory of <a href="#105" class="mim-tip-reference" title="Udall, J. N., Bloch, K. J., Walker, W. A. <strong>Transport of proteases across neonatal intestine and development of liver disease in infants with alpha-1-antitrypsin deficiency.</strong> Lancet 319: 1441-1443, 1982. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6123724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6123724</a>] [<a href="https://doi.org/10.1016/s0140-6736(82)92454-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6123724">Udall et al. (1982)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6123724+6123870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Weitz, J. I., Silverman, E. K., Thong, B., Campbell, E. J. <strong>Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype: evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha-1-proteinase inhibitor.</strong> J. Clin. Invest. 89: 766-773, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1541671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1541671</a>] [<a href="https://doi.org/10.1172/JCI115654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1541671">Weitz et al. (1992)</a> demonstrated a correlation between plasma levels of elastase-specific fibrinopeptides and PI genotype. The levels of these peptides were highest in ZZ homozygotes and intermediate in MZ heterozygotes. This was interpreted as evidence that unopposed human neutrophil elastase (ELA2; <a href="/entry/130130">130130</a>) is responsible for emphysema in patients with alpha-1-proteinase inhibitor deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1541671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#73" class="mim-tip-reference" title="Lomas, D. A., Evans, D. L., Finch, J. T., Carrell, R. W. <strong>The mechanism of Z alpha-1-antitrypsin accumulation in the liver.</strong> Nature 357: 605-607, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1608473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1608473</a>] [<a href="https://doi.org/10.1038/357605a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1608473">Lomas et al. (1992)</a> presented an explanation for the accumulation of insoluble intracellular inclusions in the ZZ homozygote. Only about 15% of the AAT protein is secreted in the plasma in ZZ homozygotes. The 85% that is not secreted accumulates in the endoplasmic reticulum (ER) of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. About 10% of newborn ZZ homozygotes develop liver disease that often leads to fatal childhood cirrhosis. <a href="#73" class="mim-tip-reference" title="Lomas, D. A., Evans, D. L., Finch, J. T., Carrell, R. W. <strong>The mechanism of Z alpha-1-antitrypsin accumulation in the liver.</strong> Nature 357: 605-607, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1608473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1608473</a>] [<a href="https://doi.org/10.1038/357605a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1608473">Lomas et al. (1992)</a> demonstrated the molecular pathology underlying this accumulation and described how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive center loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. The loop-sheet polymerization is concentration- and temperature-dependent. At times of stress, the formation of inclusions in the hepatocyte will likely overwhelm the degradative mechanisms. Antitrypsin is an acute phase protein and as such undergoes a manifold increase in association with temperature elevations during bouts of inflammation. Control of inflammation and pyrexia in ZZ homozygote infants is important. In the long-term, more specific interventions may be possible, e.g., the delivery to the hepatocyte of engineered loop peptides specific to alpha-1-antitrypsin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1608473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Liver injury in individuals with the ZZ genotype presumably results from toxic effects of the abnormal AAT molecule accumulating within the endoplasmic reticulum of liver cells; however, only 12 to 15% of individuals with this genotype develop liver disease. Therefore, <a href="#111" class="mim-tip-reference" title="Wu, Y., Whitman, I., Molmenti, E., Moore, K., Hippenmeyer, P., Perlmutter, D. H. <strong>A lag in intracellular degradation of mutant alpha-1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha-1-antitrypsin deficiency.</strong> Proc. Nat. Acad. Sci. 91: 9014-9018, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8090762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8090762</a>] [<a href="https://doi.org/10.1073/pnas.91.19.9014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8090762">Wu et al. (1994)</a> predicted that other genetic factors determine susceptibility to liver disease. To examine this hypothesis, they transduced skin fibroblasts from ZZ individuals with liver disease and from ZZ individuals without liver disease with amphotropic recombinant retroviral particles designed to express the mutant AAT*Z gene under direction of a constitutive viral promoter. Expression of the AAT gene was conferred on each fibroblast cell line. Compared to the same cell line transduced with the wildtype gene, there was selective intracellular accumulation of the mutant protein in each case. However, there was a marked delay in degradation of the mutant protein after it accumulated in the fibroblasts from ZZ individuals with liver disease ('susceptible hosts') as compared to those without liver disease ('protected hosts'). Appropriate disease controls showed that the lag in degradation in susceptible hosts is specific for the combination of the ZZ genotype and liver disease. Biochemical characteristics of the ATT*Z degradation in the protected hosts was found to be similar to those of a common ER degradation pathway previously described for T-cell receptor alpha subunits and asialoglycoprotein receptor subunits, therefore raising the possibility that the lag in degradation in the susceptible host is a defect in this common ER degradation pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8090762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>As reviewed by <a href="#74" class="mim-tip-reference" title="Lomas, D. A. <strong>New insights into the structural basis of alpha-1-antitrypsin deficiency.</strong> Quart. J. Med. 89: 807-812, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8977959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8977959</a>] [<a href="https://doi.org/10.1093/qjmed/89.11.807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8977959">Lomas (1996)</a>, inclusions in the most frequent cause of antitrypsin deficiency, the Z mutation (glu342lys; <a href="/entry/107400#0011">107400.0011</a>), is accompanied by accumulation of protein in the endoplasmic reticulum of the liver. These hepatic inclusions in turn result from a protein-protein interaction between the reactive center loop of 1 molecule and the beta-pleated sheet of a second. This loop-sheet polymerization is the basis of deficiencies associated also with mutations of C1-inhibitor (<a href="/entry/606860">606860</a>), antithrombin III (<a href="/entry/107300">107300</a>), and alpha-1-antichymotrypsin (<a href="/entry/107280">107280</a>), all of which are serine proteinase inhibitors (serpins). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8977959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#96" class="mim-tip-reference" title="Sigsgaard, T., Pedersen, O. F., Juul, S., Gravesen, S. <strong>Respiratory disorders and atopy in cotton, wool and other textile mill workers in Denmark.</strong> Am. J. Ind. Med. 22: 163-184, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415284</a>] [<a href="https://doi.org/10.1002/ajim.4700220204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1415284">Sigsgaard et al. (1992)</a> showed that in cotton workers the airborne concentration of respirable endotoxin was associated with byssinosis. Endotoxin might induce byssinosis through the release of biochemical mediators at the bronchoalveolar surface. Alpha-1-antitrypsin, which neutralizes enzymes released by granulocytes, might have a counteracting role. <a href="#95" class="mim-tip-reference" title="Sigsgaard, T., Brandslund, I., Rasmussen, J. B., Lund, E. D., Varming, H. <strong>Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.</strong> Pharmacogenetics 4: 135-141, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7920693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7920693</a>] [<a href="https://doi.org/10.1097/00008571-199406000-00004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7920693">Sigsgaard et al. (1994)</a> found that the MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM phenotype: 3/8 (38%) and 25/187 (13%). An association between the MZ phenotype and familial allergy was also found, although the association was somewhat weaker. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7920693+1415284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Carrell, R. W., Lomas, D. A. <strong>Alpha-1-antitrypsin deficiency--a model for conformational diseases.</strong> New Eng. J. Med. 346: 45-53, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11778003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11778003</a>] [<a href="https://doi.org/10.1056/NEJMra010772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11778003">Carrell and Lomas (2002)</a> suggested that alpha-1-antitrypsin deficiency is a model for conformational diseases. These are disorders due to aberrant intermolecular aggregation of proteins. Furthermore, alpha-1-antitrypsin deficiency provides a prototype for the diseases associated with abnormalities of various serpins, known collectively as the serpinopathies. Knowledge of the shared underlying conformational mechanism of protein deposition in neuronal tissues greatly increased understanding of what had previously been a daunting collection of syndromes of neurodegeneration. These included encephalopathy with neuroserpin inclusion bodies (<a href="/entry/604218">604218</a>), the Lewy-body variant of Alzheimer disease (see <a href="/entry/127750">127750</a>) with deposits of alpha-synuclein (<a href="/entry/163890">163890</a>), prion protein (<a href="/entry/176640">176640</a>) deposition in Creutzfeldt-Jakob disease (<a href="/entry/123400">123400</a>), tau protein associated with Pick bodies of frontotemporal dementia (Pick disease; <a href="/entry/172700">172700</a>), and the inclusions of huntingtin (<a href="/entry/613004">613004</a>) in Huntington disease (<a href="/entry/143100">143100</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11778003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalManagement" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#108" class="mim-tip-reference" title="Wewers, M. D., Casolaro, A., Sellers, S., Swayze, S. C., McPhaul, K. M., Wittes, J. T., Crystal, R. G. <strong>Replacement therapy for alpha-1-antitrypsin deficiency associated with emphysema.</strong> New Eng. J. Med. 316: 1055-1062, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3494198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3494198</a>] [<a href="https://doi.org/10.1056/NEJM198704233161704" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3494198">Wewers et al. (1987)</a> reported on treatment of patients with alpha-1-antitrypsin deficiency with intravenous plasma-derived AAT once a week. Although granting that a completely rigorous study was impossible, the authors concluded that infusions of AAT are safe and can reverse the biochemical abnormalities in serum and lung fluid and, further, that lifetime avoidance of cigarette smoking together with such replacement may be a logical approach to long-term therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3494198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="George, P. M., Vissers, M. C. M., Travis, J., Winterbourn, C. C., Carrell, R. W. <strong>A genetically engineered mutant of alpha-1-antitrypsin protects connective tissue from neutrophil damage and may be useful in lung disease.</strong> Lancet 324: 1426-1428, 1984. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6151045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6151045</a>] [<a href="https://doi.org/10.1016/s0140-6736(84)91623-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6151045">George et al. (1984)</a> tested the effectiveness of a genetically engineered met358-to-val mutant in the reactive center of AAT as an inhibitor of connective tissue breakdown in a model of inflammation. Degradation of basement membrane collagen was efficiently inhibited by a concentration of the mutant substance that was tenfold lower than that of the normal antitrypsin. <a href="#41" class="mim-tip-reference" title="George, P. M., Vissers, M. C. M., Travis, J., Winterbourn, C. C., Carrell, R. W. <strong>A genetically engineered mutant of alpha-1-antitrypsin protects connective tissue from neutrophil damage and may be useful in lung disease.</strong> Lancet 324: 1426-1428, 1984. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6151045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6151045</a>] [<a href="https://doi.org/10.1016/s0140-6736(84)91623-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6151045">George et al. (1984)</a> suggested the possible use of this mutant in the prophylaxis of lung dysplasias, notably emphysema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6151045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 liver represents an excellent organ for gene therapy since many genetic disorders result from deficiency of liver-specific gene products. <a href="#55" class="mim-tip-reference" title="Kay, M. A., Baley, P., Rothenberg, S., Leland, F., Fleming, L., Ponder, K. P., Liu, T., Finegold, M., Darlington, G., Pokorny, W., Woo, S. L. C. <strong>Expression of human alpha-1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.</strong> Proc. Nat. Acad. Sci. 89: 89-93, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1729724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1729724</a>] [<a href="https://doi.org/10.1073/pnas.89.1.89" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1729724">Kay et al. (1992)</a> demonstrated the autologous transplantation of canine hepatocytes transduced with a retroviral vector containing the human alpha-1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. At least 1 billion hepatocytes or 5% of the liver mass could be transplanted by the portal vasculature. Human alpha-1-antitrypsin was demonstrable in the serum of 2 dogs for 1 month. Although the serum levels of human AAT eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of the transduced hepatocytes migrated to the liver and continued to survive in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1729724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>As a model for gene therapy, <a href="#38" class="mim-tip-reference" title="Garver, R. I., Jr., Chytil, A., Courtney, M., Crystal, R. G. <strong>Clonal gene therapy: transplanted mouse fibroblast clones express human alpha-1-antitrypsin gene in vivo.</strong> Science 237: 762-764, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3497452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3497452</a>] [<a href="https://doi.org/10.1126/science.3497452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3497452">Garver et al. (1987)</a> used a retroviral vector to insert human alpha-1-antitrypsin cDNA into the genome of mouse fibroblasts. After demonstrating that the clone produced human antitrypsin after more than 100 population doublings in the absence of selection pressure, they transplanted the clone into the peritoneal cavities of nude mice. When the animals were evaluated 4 weeks later, human antitrypsin was detected in both sera and the epithelial surface of the lungs. <a href="#68" class="mim-tip-reference" title="Lemarchand, P., Jaffe, H. A., Danel, C., Cid, M. C., Kleinman, H. K., Stratford-Perricaudet, L. D., Perricaudet, M., Pavirani, A., Lecocq, J.-P., Crystal, R. G. <strong>Adenovirus-mediated transfer of a recombinant human alpha-1-antitrypsin cDNA to human endothelial cells.</strong> Proc. Nat. Acad. Sci. 89: 6482-6486, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631146</a>] [<a href="https://doi.org/10.1073/pnas.89.14.6482" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631146">Lemarchand et al. (1992)</a> reported experiments supporting the feasibility of in vivo human gene transfer of recombinant human AAT cDNA to endothelial cells by means of replication-deficiency adenovirus vectors. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1631146+3497452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#97" class="mim-tip-reference" title="Song, S., Morgan, M., Ellis, T., Poirier, A., Chesnut, K., Wang, J., Brantly, M., Muzyczka, N., Byrne, B. J., Atkinson, M., Flotte, T. R. <strong>Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors.</strong> Proc. Nat. Acad. Sci. 95: 14384-14388, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9826709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9826709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9826709[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.95.24.14384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9826709">Song et al. (1998)</a> described experiments in mice in which recombinant adeno-associated virus (AAV) vectors were used to transduce skeletal muscle as a platform for secretion of alpha-1-antitrypsin and other therapeutic proteins. The utility of this approach for treating AAT deficiency was tested in murine myocytes in vitro and in vivo. Serum concentrations were 100,000-fold higher than those previously observed with AAV vectors in muscle and at levels that would be therapeutic if achieved in humans. High-level expression was delayed for several weeks but was sustained for over 15 weeks. Immune responses were dependent upon the mouse strain and the vector dosage. These data suggested that recombinant AAV vector transduction of skeletal muscle could provide a means for replacing AAT or other essential serum proteins but that immune responses may be elicited under certain conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9826709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#110" class="mim-tip-reference" title="Wilcke, J. T. R., Seersholm, N., Kok-Jensen, A., Dirksen, A. <strong>Transmitting genetic risk information in families: attitudes about disclosing the identity of relatives.</strong> Am. J. Hum. Genet. 65: 902-909, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441594</a>] [<a href="https://doi.org/10.1086/302531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441594">Wilcke et al. (1999)</a> examined attitudes about disclosing the identities of family members to a physician to ensure diffusion of genetic risk information within affected families, by means of a questionnaire study of Danish patients with alpha-1-antitrypsin deficiency (symbolized A1AD), their relatives, and a control group of Danish citizens. Only 2.8% objected to disclosing the identity of children, 9.1% objected to disclosing the identity of parents, and 6.7% objected to disclosing the identity of sibs. When genetic tests were offered to a sister, 75.4% of screened individuals with severe A1AD (phenotype 'piZ') and 66.8% of piZ probands thought that the physician should say who was ill. Important reasons for informing a sister at risk were, for 58%, the opportunity to prevent disease and, for 41% of piZ-probands, the opportunity to maintain openness in the family and to avoid uncertainty. The women were less prone to disclose the identity of sibs. <a href="#110" class="mim-tip-reference" title="Wilcke, J. T. R., Seersholm, N., Kok-Jensen, A., Dirksen, A. <strong>Transmitting genetic risk information in families: attitudes about disclosing the identity of relatives.</strong> Am. J. Hum. Genet. 65: 902-909, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441594</a>] [<a href="https://doi.org/10.1086/302531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441594">Wilcke et al. (1999)</a> concluded that the genetic counselor should ensure that relatives are properly informed about their risk of a severe genetic disorder, such as A1AD, in which disability can be prevented by change of lifestyle or by careful management. Because of a certain amount of ambivalence encountered in affected families, they recognized the necessity to exercise flexibility and responsiveness to individual circumstances when asking for relatives' identity and when approaching relatives. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#50" 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 is the PiZ mouse, developed by <a href="#27" 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 of 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="#50" 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, and also provided a proof of principle for therapeutic use of autophagy enhancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3264419+20522742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#112" class="mim-tip-reference" title="Yusa, K., Rashid, S. T., Strick-Marchand, H., Varela, I., Liu, P.-Q., Paschon, D. E., Miranda, E., Ordonez, A., Hannan, N. R. F., Rouhani, F. J., Darche, S., Alexander, G., Marciniak, S. J., Fusaki, N., Hasegawa, M., Holmes, M. C., Di Santo, J. P., Lomas, D. A., Bradley, A., Vallier, L. <strong>Targeted gene correction of alpha-1-antitrypsin deficiency in induced pluripotent stem cells.</strong> Nature 478: 391-394, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21993621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21993621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21993621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21993621">Yusa et al. (2011)</a> showed that a combination of zinc finger nucleases and piggyBac technology in human induced pluripotent stem cells (iPSCs) can achieve biallelic correction of a point mutation (glu342 to lys; <a href="/entry/107400#0011">107400.0011</a>) in the alpha-1-antitrypsin gene that is responsible for alpha-1-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of alpha-1-antitrypsin in subsequently derived liver cells in vitro and in vivo. <a href="#112" class="mim-tip-reference" title="Yusa, K., Rashid, S. T., Strick-Marchand, H., Varela, I., Liu, P.-Q., Paschon, D. E., Miranda, E., Ordonez, A., Hannan, N. R. F., Rouhani, F. J., Darche, S., Alexander, G., Marciniak, S. J., Fusaki, N., Hasegawa, M., Holmes, M. C., Di Santo, J. P., Lomas, D. A., Bradley, A., Vallier, L. <strong>Targeted gene correction of alpha-1-antitrypsin deficiency in induced pluripotent stem cells.</strong> Nature 478: 391-394, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21993621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21993621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21993621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21993621">Yusa et al. (2011)</a> stated that this approach was significantly more efficient than any other gene-targeting technology then available and crucially prevented contamination of the host genome with residual nonhuman sequences. The authors concluded that their results provided the first proof of principle for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21993621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Family studies indicated recessive inheritance of antitrypsin deficiency.</p><p>In early studies, heterozygotes, who can be detected chemically, were unaffected clinically; later studies suggested that heterozygosity may predispose to lung disease (<a href="#72" class="mim-tip-reference" title="Lieberman, J. <strong>Heterozygous and homozygous alpha-1-antitrypsin deficiency in patients with pulmonary emphysema.</strong> New Eng. J. Med. 281: 279-284, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4183173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4183173</a>] [<a href="https://doi.org/10.1056/NEJM196908072810601" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4183173">Lieberman, 1969</a>). For example, of 12 patients with obstructive lung disease present before age 40 years, 2 were judged by <a href="#103" class="mim-tip-reference" title="Tarkoff, M. P., Kueppers, F., Miller, W. F. <strong>Pulmonary emphysema and alpha-1-antitrypsin deficiency.</strong> Am. J. Med. 45: 220-228, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5666650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5666650</a>] [<a href="https://doi.org/10.1016/0002-9343(68)90040-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5666650">Tarkoff et al. (1968)</a> to be homozygous for the deficiency and 1 heterozygous. Among 103 patients, <a href="#62" class="mim-tip-reference" title="Kueppers, F., Fallat, R., Larson, R. K. <strong>Obstructive lung diseases and alpha-antitrypsin deficiency gene heterozygosity.</strong> Science 165: 899-901, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5816326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5816326</a>] [<a href="https://doi.org/10.1126/science.165.3896.899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5816326">Kueppers et al. (1969)</a> found 5 homozygotes and 25 heterozygotes for the deficiency gene. They suggested that, especially in males, heterozygosity may predispose to chronic obstructive lung disease. <a href="#99" class="mim-tip-reference" title="Stevens, P. M., Hnilica, V., Johnson, P. C., Bell, R. L. <strong>Pathophysiology of hereditary emphysema.</strong> Ann. Intern. Med. 74: 672-680, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4104410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4104410</a>] [<a href="https://doi.org/10.7326/0003-4819-74-5-672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4104410">Stevens et al. (1971)</a> concluded that heterozygotes may develop emphysema qualitatively like that in homozygotes, but at a later age. The importance of prompt treatment of respiratory infections and avoidance of proteolytic aerosols, smoking and employment entailing exposure to respiratory irritants are important preventive measures in these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4104410+5816326+4183173+5666650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>To study the question of the role of alpha-1-antitrypsin heterozygosity in the etiopathogenesis of chronic obstructive pulmonary disease (COPD) and to obviate the difficulties of precise diagnosis, <a href="#60" class="mim-tip-reference" title="Klasen, E. C., Biemond, I., Laros, C. D. <strong>Alpha-1-antitrypsin deficiency and the flaccid lung syndrome: the heterozygote controversy.</strong> Clin. Genet. 29: 211-215, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3486059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3486059</a>]" pmid="3486059">Klasen et al. (1986)</a> used a well-defined subgroup suffering from so-called 'flaccid lung.' In these persons, there is a loss of elasticity of the lung parenchyma with high compliance. Flaccid lung can be found with a high vital capacity, with spontaneous pneumothorax, in patients with giant bullae, and in all patients with lung emphysema. <a href="#60" class="mim-tip-reference" title="Klasen, E. C., Biemond, I., Laros, C. D. <strong>Alpha-1-antitrypsin deficiency and the flaccid lung syndrome: the heterozygote controversy.</strong> Clin. Genet. 29: 211-215, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3486059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3486059</a>]" pmid="3486059">Klasen et al. (1986)</a> found a relative risk of 12.5 for PI ZZ persons and 1.8 for MZ persons. They concluded that the risk of MZ persons compared to MM persons is almost negligible and that whether the MZ person develops lung disease is probably highly influenced by environmental and perhaps other genetic factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3486059" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Dahl, M., Tybjaerg-Hansen, A., Lange, P., Vestbo, J., Nordestgaard, B. G. <strong>Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha-1-antitrypsin MZ heterozygotes: a longitudinal study of the general population.</strong> Ann. Intern. Med. 136: 270-279, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11848724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11848724</a>] [<a href="https://doi.org/10.7326/0003-4819-136-4-200202190-00006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11848724">Dahl et al. (2002)</a> reported on a study in Copenhagen to determine whether the MZ intermediate alpha-1-antitrypsin deficiency affects pulmonary function and disease. They randomly selected 9,187 adults from the Danish general population and followed them over a 21-year period; 451 (4.9%) carried the MZ genotype. Plasma antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype. They found that MZ heterozygotes had a slightly greater rate of decrease in FEV1 measure of pulmonary function and were modestly overrepresented among persons with airway obstruction and chronic obstructive pulmonary disease (COPD; <a href="/entry/606963">606963</a>). They estimated that in the population at large, MZ heterozygosity may account for a fraction of COPD cases (on the order of 2%), similar to the percentage of persons with COPD who have the severe but rare ZZ genotype. Because the incidence of heterozygosity is so much higher than that of homozygosity, alpha-1-antitrypsin heterozygosity is as important a public health problem as homozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11848724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>From study of 60-year-old twins with ZZ alpha-1-antitrypsin deficiency, one a heavy smoker who developed severe emphysema and the other a lifelong nonsmoker who was asymptomatic with only mild evidence of obstructive pulmonary disease, <a href="#56" class="mim-tip-reference" title="Kennedy, M., Brett, W. <strong>Monozygotic twins with alpha-1-antitrypsin deficiency. (Letter)</strong> Lancet 326: 527-528, 1985. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2857896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2857896</a>] [<a href="https://doi.org/10.1016/s0140-6736(85)92133-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2857896">Kennedy and Brett (1985)</a> demonstrated the importance of the environmental factor. A brother died at age 40 years of emphysema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2857896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#91" 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="#17" 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="#19" 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>Alpha-1-antitrypsin deficiency is said to be rare among Japanese. <a href="#54" 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/?cmd=link&linkname=pubmed_pubmed&from_uid=7227484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="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="#25" 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 in Europe demonstrated that they occur mainly among those of European stock. <a href="#52" 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="#9" 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><p>On the basis of data from previously published genetic epidemiologic studies, <a href="#24" class="mim-tip-reference" title="de Serres, F. J., Blanco, I., Fernandez-Bustillo, E. <strong>Genetic epidemiology of alpha-1 antitrypsin deficiency in southern Europe: France, Italy, Portugal and Spain.</strong> Clin. Genet. 63: 490-509, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12786756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12786756</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00078.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12786756">de Serres et al. (2003)</a> estimated the frequency of AAT deficiency in France, Italy, Portugal, and Spain. In another report, <a href="#23" class="mim-tip-reference" title="de Serres, F. J., Blanco, I., Fernandez-Bustillo, E. <strong>Genetic epidemiology of alpha-1 antitrypsin deficiency in North America and Australia/New Zealand: Australia, Canada, New Zealand and the United States of America.</strong> Clin. Genet. 64: 382-397, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14616761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14616761</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00143.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14616761">de Serres et al. (2003)</a> focused on the distribution of the PiS and PiZ deficiency alleles in Australia, Canada, New Zealand, and the United States. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12786756+14616761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 15,484 ethnically diverse individuals screened for alpha-1 antitrypsin deficiency carrier status, <a href="#67" class="mim-tip-reference" title="Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S. <strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong> Genet. Med. 15: 178-186, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22975760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22975760</a>] [<a href="https://doi.org/10.1038/gim.2012.114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22975760">Lazarin et al. (2013)</a> identified 1,178 carriers (7.6%), for an estimated carrier frequency of approximately 1 in 13. Forty-seven 'carrier couples' were identified. Thirty-eight individuals were identified as homozygotes or compound heterozygotes. Among 8,570 individuals of northern European origin, <a href="#67" class="mim-tip-reference" title="Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S. <strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong> Genet. Med. 15: 178-186, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22975760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22975760</a>] [<a href="https://doi.org/10.1038/gim.2012.114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22975760">Lazarin et al. (2013)</a> identified a carrier frequency of 1 in 10. Among 747 individuals of east Asian origin, the carrier frequency was 1 in 249. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22975760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="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>Deficiency of protease inhibitor activity is associated with several of the electrophoretic variants of serum alpha-1-antitrypsin; <a href="#4" 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> first suggested that the genes for electrophoretic variants are allelic with the deficiency gene. <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'})"><span class="glyphicon 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="#19" 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="/entry/107400#0001">107400.0001</a>-<a href="/entry/107400#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="#82" 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="/entry/107400#0002">107400.0002</a>) and that with alanine at position 213 (M1A; <a href="/entry/107400#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="#19" 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="/entry/107400#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="/entry/107400#0011">107400.0011</a>), which occurs on an M1A (ala213; <a href="/entry/107400#0001">107400.0001</a>) haplotype background (<a href="#81" 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="#25" 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="#52" 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>Another common AAT deficiency allele is the S allele (glu264-to-val; <a href="/entry/107400#0013">107400.0013</a>), which occurs on an M1V (val213; <a href="/entry/107400#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="#21" 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="/entry/107400#0012">107400.0012</a>) or only emphysema (e.g., Pi M(Procida); <a href="/entry/107400#0016">107400.0016</a>). Some of the rare deficiency alleles have been found in Japanese (e.g., Pi S(Iiyama); <a href="/entry/107400#0039">107400.0039</a>).</p><p>By means of isoelectric focusing, <a href="#106" class="mim-tip-reference" title="Weber, W., Weidinger, S. <strong>PI S-Cologne: a new variant in the alpha-1-antitrypsin system.</strong> Hum. Genet. 80: 102, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262085</a>] [<a href="https://doi.org/10.1007/BF00451468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3262085">Weber and Weidinger (1988)</a> found a PI variant that they called PI S (Cologne). A father and daughter were heterozygous. Alpha-1-antitrypsin concentrations were within the normal range. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3262085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Null AAT alleles are rare but have been found in all populations. <a href="#39" 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="#84" 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="/entry/107400#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="#5" class="mim-tip-reference" title="Bamforth, F. J., Kalsheker, N. A. <strong>Alpha-1 antitrypsin deficiency due to Pi null: clinical presentation and evidence for molecular heterogeneity.</strong> J. Med. Genet. 25: 83-87, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831367</a>] [<a href="https://doi.org/10.1136/jmg.25.2.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2831367">Bamforth and Kalsheker (1988)</a> discussed a rare Pi null allele that in homozygous state leads to pulmonary emphysema at an early age. In 3 families, all the affected individuals presented in early childhood with recurrent chest infections and wheezing, presumably related to passive smoking. Even though there was no detectable AAT, no partial or complete deletion of the gene could be identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2831367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#93" 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="/entry/107400#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 (M358R; <a href="/entry/107400#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 and results in a bleeding disorder (<a href="#69" 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="#85" 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=6604220+412531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>
|
|
The most widely recognized candidate gene in COPD (see <a href="/entry/606963">606963</a>) is SERPINA1, although it has been suggested that SERPINA3 (<a href="/entry/107280">107280</a>) may also play a role. <a href="#13" 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><p><strong><em>Reviews</em></strong></p><p>
|
|
<a href="#20" 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> gave a comprehensive review of the pathogenetic relationship between AAT deficiency and emphysema and liver disease, including a detailed listing of the various mutations that have been identified and a discussion of the possibilities for therapy. <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="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="#76" 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="#43" 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 Siiyama variant antitrypsin (<a href="/entry/107400#0039">107400.0039</a>) failed to complement nec-null mutations and demonstrated a dominant temperature-dependent inactivation of the wildtype nec allele. <a href="#43" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#31" class="mim-tip-reference" title="Eriksson, S. <strong>Alpha-1-antitrypsin deficiency: lessons learned from the bedside to the gene and back again.</strong> Chest 95: 181-189, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2642407/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2642407</a>] [<a href="https://doi.org/10.1378/chest.95.1.181" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2642407">Eriksson (1989)</a> gave an interesting historical account including the pedigree of his first family (<a href="#30" class="mim-tip-reference" title="Eriksson, S. <strong>Studies in alpha 1-antitrypsin deficiency.</strong> Acta Med. Scand. Suppl. 432: 1-85, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4160491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4160491</a>]" pmid="4160491">Eriksson, 1965</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2642407+4160491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Several reports (<a href="#6" class="mim-tip-reference" title="Bell, O. F., Carrell, R. W. <strong>Basis of the defect in alpha-1-antitrypsin deficiency.</strong> Nature 243: 410-411, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4542721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4542721</a>] [<a href="https://doi.org/10.1038/243410a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4542721">Bell and Carrell, 1973</a>; <a href="#63" class="mim-tip-reference" title="Kuhlenschmidt, M. S., Yunis, E. J., Iammarino, R. M., Turco, S. J., Peters, S. P., Glew, R. H. <strong>Demonstration of sialyltransferase deficiency in the serum of a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis.</strong> Lab. Invest. 31: 413-419, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4547176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4547176</a>]" pmid="4547176">Kuhlenschmidt et al., 1974</a>; <a href="#29" class="mim-tip-reference" title="Eriksson, S., Larsson, C. <strong>Purification and partial characterization of PAS-positive inclusion bodies from the liver in alpha-1-antitrypsin deficiency.</strong> New Eng. J. Med. 292: 176-180, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/45843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">45843</a>] [<a href="https://doi.org/10.1056/NEJM197501232920403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="45843">Eriksson and Larsson, 1975</a>) had suggested that the defect may be in a sialyltransferase and that deficiency of antitrypsin in the blood is the result of impaired secretion from hepatocytes, increased clearance of the undersialated protein, or both. It is difficult to see how this could cause codominant inheritance or account for the different types that appear to be the products of at least 30 different alleles, unless an amino acid substitution interferes with sialidation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4547176+4542721+45843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Arnaud1977" class="mim-tip-reference" title="Arnaud, P., Galbraith, R. M., Faulk, W. P. <strong>Increased frequency of the MZ phenotype of alpha-1-protease inhibitor in juvenile chronic polyarthritis.</strong> J. Clin. Invest. 60: 1442-1444, 1977.">Arnaud et al. (1977)</a>; <a href="#Chan1978" class="mim-tip-reference" title="Chan, C. H., Steer, C. J., Vergalla, J., Jones, E. A. <strong>Alpha-1-antitrypsin deficiency with cirrhosis associated with the protease inhibitor phenotype SZ.</strong> Am. J. Med. 65: 978-986, 1978.">Chan et al. (1978)</a>; <a href="#Cox2001">Cox (2001)</a>; <a href="#Falk1970" class="mim-tip-reference" title="Falk, G. A. <strong>Chronic obstructive pulmonary disease and heterozygous alpha-1-antitrypsin deficiency. (Editorial)</strong> Ann. Intern. Med. 72: 595-596, 1970.">Falk and
|
|
Briscoe (1970)</a>; <a href="#Falk1970" class="mim-tip-reference" title="Falk, G. A. <strong>Chronic obstructive pulmonary disease and heterozygous alpha-1-antitrypsin deficiency. (Editorial)</strong> Ann. Intern. Med. 72: 595-596, 1970.">Falk (1970)</a>; <a href="#Freeman1976" class="mim-tip-reference" title="Freeman, H. J., Weinstein, W. M., Shnitka, T. K., Crockford, P. M., Herbert, F. A. <strong>Alpha-1-antitrypsin deficiency and pancreatic fibrosis.</strong> Ann. Intern. Med. 85: 73-76, 1976.">Freeman et al. (1976)</a>; <a href="#Guenter1971" class="mim-tip-reference" title="Guenter, C. A., Welch, M. H., Hammarsten, J. F. <strong>Alpha-1-antitrypsin deficiency and pulmonary emphysema.</strong> Annu. Rev. Med. 22: 283-292, 1971.">Guenter et al.
|
|
(1971)</a>; <a href="#Hall1976" class="mim-tip-reference" title="Hall, W. J., Hyde, R. W., Schwartz, R. H., Mudholkar, G. S., Webb, D. R., Chaubey, Y. P., Townes, P. L. <strong>Pulmonary abnormalities in intermediate alpha-1-antitrypsin deficiency.</strong> J. Clin. Invest. 58: 1069-1077, 1976.">Hall et al. (1976)</a>; <a href="#Hepper1969" class="mim-tip-reference" title="Hepper, N. G., Black, L. F., Gleich, G. J., Kueppers, F. <strong>The prevalence of alpha-1-antitrypsin deficiency in selected groups of patients with chronic obstructive lung disease.</strong> Mayo Clin. Proc. 44: 697-710, 1969.">Hepper et al. (1969)</a>; <a href="#Hodges1981" class="mim-tip-reference" title="Hodges, J. R., Millward-Sadler, G. H., Barbatis, C., Wright, R. <strong>Heterozygous MZ alpha-1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenic cirrhosis.</strong> New Eng. J. Med. 304: 557-560, 1981.">Hodges et al.
|
|
(1981)</a>; <a href="#Jeppsson1975" class="mim-tip-reference" title="Jeppsson, J.-O., Larsson, C., Eriksson, S. <strong>Characterization of alpha-1-antitrypsin in the inclusion bodies from the liver in alpha-1-antitrypsin deficiency.</strong> New Eng. J. Med. 293: 576-579, 1975.">Jeppsson et al. (1975)</a>; <a href="#Kew1978" class="mim-tip-reference" title="Kew, M. C., Turnbull, R., Prinsloo, I. <strong>Alpha-1-antitrypsin deficiency and hepatocellular cancer.</strong> Brit. J. Cancer 37: 635-638, 1978.">Kew et al. (1978)</a>; <a href="#Kueppers1967" class="mim-tip-reference" title="Kueppers, F., Bearn, A. G. <strong>An inherited alpha-1-antitrypsin variant.</strong> Humangenetik 4: 217-220, 1967.">Kueppers and Bearn
|
|
(1967)</a>; <a href="#Langley1979" class="mim-tip-reference" title="Langley, C. E., Berninger, R. W., Wolfson, S. L., Talamo, R. C. <strong>An unusual type of alpha-1-antitrypsin deficiency in a child.</strong> Johns Hopkins Med. J. 144: 161-165, 1979.">Langley et al. (1979)</a>; <a href="#Lieberman1971" class="mim-tip-reference" title="Lieberman, J., Mittman, C., Kent, J. R. <strong>Screening for heterozygous alpha-1-antitrypsin deficiency. III. A provocative test with diethylstilbestrol and effect of oral contraceptives.</strong> JAMA 217: 1198-1206, 1971.">Lieberman et al. (1971)</a>; <a href="#Long1984" 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.">Long et al.
|
|
(1984)</a>; <a href="#Meisen1988" class="mim-tip-reference" title="Meisen, C., Higuchi, M., Brautigam, S., Driesel, A. J., Blandfort, M., Olek, K. <strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency using oligonucleotide probe analysis.</strong> Hum. Genet. 79: 190-192, 1988.">Meisen et al. (1988)</a>; <a href="#Morse1978" class="mim-tip-reference" title="Morse, J. O. <strong>Alpha-1-antitrypsin deficiency.</strong> New Eng. J. Med. 299: 1045-1048 and 1099-1105, 1978.">Morse (1978)</a>; <a href="#Neumann1976" class="mim-tip-reference" title="Neumann, F., Meirom, R., Rattner, D., Trainin, Z., Klopfer, U., Nobel, T. A. <strong>Animal model of human disease: alpha-1-antitrypsin deficiency.</strong> Am. J. Path. 84: 427-430, 1976.">Neumann et al. (1976)</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="#Perrault1979" class="mim-tip-reference" title="Perrault, J. L., Malo, J.-L., Bake, B., Renzi, G., Grassino, A. <strong>Alpha-1-antitrypsin deficiency: genetic, clinical and functional correlations in a three generation family.</strong> Respiration 37: 291-300, 1979.">Perrault et al. (1979)</a>; <a href="#Pierce1969" class="mim-tip-reference" title="Pierce, J. A., Eisen, A. Z., Dhingra, H. K. <strong>Relationship of antitrypsin deficiency to the pathogenesis of emphysema.</strong> Trans. Assoc. Am. Phys. 82: 87-97, 1969.">Pierce et al. (1969)</a>; <a href="#Rodriguez-Soriano1978" class="mim-tip-reference" title="Rodriguez-Soriano, J., Fidalgo, I., Camarero, C., Vallo, A., Oliveros, R. <strong>Juvenile cirrhosis and membranous glomerulonephritis in a child with alpha-1-antitrypsin deficiency PiSZ.</strong> Acta Paediat. Scand. 67: 793-796, 1978.">Rodriguez-Soriano et al. (1978)</a>; <a href="#Rosenthal1979" class="mim-tip-reference" title="Rosenthal, P., Liebman, W. M., Thaler, M. M. <strong>Alpha-1-antitrypsin deficiency and severe infantile liver disease.</strong> Am. J. Dis. Child. 133: 1195-1196, 1979.">Rosenthal et al. (1979)</a>; <a href="#Schmitt1975" class="mim-tip-reference" title="Schmitt, M. G., Jr., Phillips, R. B., Matzen, R. N., Rodey, G. <strong>Alpha-1-antitrypsin deficiency: a study of the relationship between the Pi system and genetic markers.</strong> Am. J. Hum. Genet. 27: 315-321, 1975.">Schmitt et
|
|
al. (1975)</a>; <a href="#Sharp1969" class="mim-tip-reference" title="Sharp, H. L., Bridges, R. A., Krivit, W., Freier, E. F. <strong>Cirrhosis associated with alpha-1-antitrypsin deficiency: a previously unrecognized inherited disorder.</strong> J. Lab. Clin. Med. 73: 934-939, 1969.">Sharp et al. (1969)</a>; <a href="#Starzl1983" class="mim-tip-reference" title="Starzl, T. E., Porter, K. A., Francavilla, A., Iwatsuki, S. <strong>Reversal of hepatic alpha-1-antitrypsin deposition after portacaval shunt.</strong> Lancet 322: 424-426, 1983. Note: Originally Volume II.">Starzl et al. (1983)</a>; <a href="#Stockley1979" class="mim-tip-reference" title="Stockley, R. A. <strong>Alpha-1-antitrypsin phenotypes in cor pulmonale due to chronic obstructive airways disease.</strong> Quart. J. Med. 48: 419-428, 1979.">Stockley
|
|
(1979)</a>; <a href="#Talamo1968" class="mim-tip-reference" title="Talamo, R. C., Allen, J. D., Kahan, M. G., Austen, K. F. <strong>Hereditary alpha-1-antitrypsin deficiency.</strong> New Eng. J. Med. 278: 345-351, 1968.">Talamo et al. (1968)</a>; <a href="#Talamo1973" class="mim-tip-reference" title="Talamo, R. C., Feingold, M. <strong>Infantile cirrhosis with hereditary alpha-1-antitrypsin deficiency.</strong> Am. J. Dis. Child. 125: 845-849, 1973.">Talamo and Feingold (1973)</a>; <a href="#Townley1970" class="mim-tip-reference" title="Townley, R. G., Ryning, F., Lynch, H. T., Brody, A. W. <strong>Obstructive lung disease in hereditary alpha-1-antitrypsin deficiency.</strong> JAMA 214: 325-331, 1970.">Townley et
|
|
al. (1970)</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="Aagenaes1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aagenaes, O., Matlary, A., Elgjo, K., Munthe, E., Fagerhol, M.
|
|
<strong>Neonatal cholestasis in alpha-1-antitrypsin deficient children: clinical, genetic, histological and immunohistochemical findings.</strong>
|
|
Acta Paediat. Scand. 61: 632-642, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4117022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1651-2227.1972.tb15960.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Abbott1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Abbott, C. M., McMahon, C. J., Whitehouse, D. B., Povey, S.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency using polymerase chain reaction. (Letter)</strong>
|
|
Lancet 331: 763-764, 1988. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2895285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2895285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2895285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(88)91565-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Arnaud1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Arnaud, P., Galbraith, R. M., Faulk, W. P.
|
|
<strong>Increased frequency of the MZ phenotype of alpha-1-protease inhibitor in juvenile chronic polyarthritis.</strong>
|
|
J. Clin. Invest. 60: 1442-1444, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/334801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">334801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=334801" 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/JCI108906" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" 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="5" class="mim-anchor"></a>
|
|
<a id="Bamforth1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bamforth, F. J., Kalsheker, N. A.
|
|
<strong>Alpha-1 antitrypsin deficiency due to Pi null: clinical presentation and evidence for molecular heterogeneity.</strong>
|
|
J. Med. Genet. 25: 83-87, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831367</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2831367" 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.25.2.83" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bell1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bell, O. F., Carrell, R. W.
|
|
<strong>Basis of the defect in alpha-1-antitrypsin deficiency.</strong>
|
|
Nature 243: 410-411, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4542721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4542721</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4542721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/243410a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bell1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bell, R. S.
|
|
<strong>The radiographic manifestations of alpha-1 antitrypsin deficiency: an important recognizable pattern of chronic obstructive pulmonary disease (COPD).</strong>
|
|
Radiology 95: 19-24, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5417042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5417042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5417042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1148/95.1.19" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Berg1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berg, N. O., Eriksson, S.
|
|
<strong>Liver disease in adults with alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 287: 1264-1267, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4117996" 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/NEJM197212212872502" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" 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="10" 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="11" class="mim-anchor"></a>
|
|
<a id="Carrell2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carrell, R. W., Lomas, D. A.
|
|
<strong>Alpha-1-antitrypsin deficiency--a model for conformational diseases.</strong>
|
|
New Eng. J. Med. 346: 45-53, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11778003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11778003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11778003" 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/NEJMra010772" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Chan1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, C. H., Steer, C. J., Vergalla, J., Jones, E. A.
|
|
<strong>Alpha-1-antitrypsin deficiency with cirrhosis associated with the protease inhibitor phenotype SZ.</strong>
|
|
Am. J. Med. 65: 978-986, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/217266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">217266</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=217266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9343(78)90750-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" 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="14" 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="15" 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="16" 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="17" 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="18" 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 (pub.) 2001. Pp. 5559-5584.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" 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="20" 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="21" 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="22" class="mim-anchor"></a>
|
|
<a id="Dahl2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dahl, M., Tybjaerg-Hansen, A., Lange, P., Vestbo, J., Nordestgaard, B. G.
|
|
<strong>Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha-1-antitrypsin MZ heterozygotes: a longitudinal study of the general population.</strong>
|
|
Ann. Intern. Med. 136: 270-279, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11848724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11848724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11848724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-136-4-200202190-00006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="de Serres2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Serres, F. J., Blanco, I., Fernandez-Bustillo, E.
|
|
<strong>Genetic epidemiology of alpha-1 antitrypsin deficiency in North America and Australia/New Zealand: Australia, Canada, New Zealand and the United States of America.</strong>
|
|
Clin. Genet. 64: 382-397, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14616761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14616761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14616761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2003.00143.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="de Serres2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Serres, F. J., Blanco, I., Fernandez-Bustillo, E.
|
|
<strong>Genetic epidemiology of alpha-1 antitrypsin deficiency in southern Europe: France, Italy, Portugal and Spain.</strong>
|
|
Clin. Genet. 63: 490-509, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12786756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12786756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12786756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2003.00078.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" 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="26" class="mim-anchor"></a>
|
|
<a id="Dry1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dry, P. J.
|
|
<strong>Rapid detection of alpha-1-antitrypsin deficiency by analysis of a PCR-induced TaqI restriction site.</strong>
|
|
Hum. Genet. 87: 742-744, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1937480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1937480</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1937480" 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/BF00201739" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" 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="28" class="mim-anchor"></a>
|
|
<a id="Eriksson1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, S., Carlson, J., Velez, R.
|
|
<strong>Risk of cirrhosis and primary liver cancer in alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 314: 736-739, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485248" 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/NEJM198603203141202" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Eriksson1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, S., Larsson, C.
|
|
<strong>Purification and partial characterization of PAS-positive inclusion bodies from the liver in alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 292: 176-180, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/45843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">45843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=45843" 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/NEJM197501232920403" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Eriksson1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, S.
|
|
<strong>Studies in alpha 1-antitrypsin deficiency.</strong>
|
|
Acta Med. Scand. Suppl. 432: 1-85, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4160491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4160491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4160491" 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="Eriksson1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, S.
|
|
<strong>Alpha-1-antitrypsin deficiency: lessons learned from the bedside to the gene and back again.</strong>
|
|
Chest 95: 181-189, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2642407/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2642407</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2642407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1378/chest.95.1.181" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Falk1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Falk, G. A., Briscoe, W. A.
|
|
<strong>Alpha-1-antitrypsin deficiency in chronic obstructive pulmonary disease.</strong>
|
|
Ann. Intern. Med. 72: 427-429, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4906114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4906114</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4906114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-72-3-427" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Falk1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Falk, G. A.
|
|
<strong>Chronic obstructive pulmonary disease and heterozygous alpha-1-antitrypsin deficiency. (Editorial)</strong>
|
|
Ann. Intern. Med. 72: 595-596, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4191180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4191180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4191180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-72-4-595" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Fargion1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fargion, S., Klasen, E. C., Lalatta, F., Sangalli, G., Tommasini, M., Fiorelli, G.
|
|
<strong>Alpha-1-antitrypsin in patients with carcinoma and chronic active hepatitis.</strong>
|
|
Clin. Genet. 19: 134-139, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6258829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6258829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6258829" 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.1399-0004.1981.tb00684.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Fortin1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fortin, P. R., Fraser, R. S., Watts, C. S., Esdaile, J. M.
|
|
<strong>Alpha-1 antitrypsin deficiency and systemic necrotizing vasculitis.</strong>
|
|
J. Rheum. 18: 1613-1616, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1684994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1684994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1684994" 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="36" class="mim-anchor"></a>
|
|
<a id="Freeman1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Freeman, H. J., Weinstein, W. M., Shnitka, T. K., Crockford, P. M., Herbert, F. A.
|
|
<strong>Alpha-1-antitrypsin deficiency and pancreatic fibrosis.</strong>
|
|
Ann. Intern. Med. 85: 73-76, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1084722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1084722</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1084722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-85-1-73" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Gans1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gans, H., Sharp, H. L., Tan, B. H.
|
|
<strong>Antiprotease deficiency and familial infantile liver cirrhosis.</strong>
|
|
Surg. Gynec. Obstet. 129: 289-299, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4240153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4240153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4240153" 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="Garver1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garver, R. I., Jr., Chytil, A., Courtney, M., Crystal, R. G.
|
|
<strong>Clonal gene therapy: transplanted mouse fibroblast clones express human alpha-1-antitrypsin gene in vivo.</strong>
|
|
Science 237: 762-764, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3497452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3497452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3497452" 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.3497452" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" 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="40" class="mim-anchor"></a>
|
|
<a id="Geddes1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Geddes, D. M., Webley, M., Brewerton, D. A., Turton, C. W., Turner-Warwick, M., Murphy, A. H., Ward, A. M.
|
|
<strong>Alpha-1-antitrypsin phenotypes in fibrosing alveolitis and rheumatoid arthritis.</strong>
|
|
Lancet 310: 1049-1051, 1977. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/72955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">72955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=72955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(77)91883-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="George1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, P. M., Vissers, M. C. M., Travis, J., Winterbourn, C. C., Carrell, R. W.
|
|
<strong>A genetically engineered mutant of alpha-1-antitrypsin protects connective tissue from neutrophil damage and may be useful in lung disease.</strong>
|
|
Lancet 324: 1426-1428, 1984. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6151045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6151045</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6151045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(84)91623-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Gherardi1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gherardi, G. J.
|
|
<strong>Alpha-1-antitrypsin deficiency and its effect on the liver.</strong>
|
|
Hum. Path. 2: 173-175, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5095241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5095241</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5095241" 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/s0046-8177(71)80026-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" 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="44" class="mim-anchor"></a>
|
|
<a id="Guenter1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guenter, C. A., Welch, M. H., Hammarsten, J. F.
|
|
<strong>Alpha-1-antitrypsin deficiency and pulmonary emphysema.</strong>
|
|
Annu. Rev. Med. 22: 283-292, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4944420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4944420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4944420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.me.22.020171.001435" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Hall1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, W. J., Hyde, R. W., Schwartz, R. H., Mudholkar, G. S., Webb, D. R., Chaubey, Y. P., Townes, P. L.
|
|
<strong>Pulmonary abnormalities in intermediate alpha-1-antitrypsin deficiency.</strong>
|
|
J. Clin. Invest. 58: 1069-1077, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1086856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1086856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1086856" 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/JCI108558" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Harrison1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harrison, H. H., Miller, K. L., Whitington, P. F.
|
|
<strong>Improved detection, via ISO-DALT two-dimensional electrophoresis, of 'low Z expressor' individuals with alpha-1-antitrypsin MZ phenotype.</strong>
|
|
Clin. Chem. 36: 1850-1851, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2208671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2208671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2208671" 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="47" class="mim-anchor"></a>
|
|
<a id="Hejtmancik1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hejtmancik, J. F., Sifers, R. N., Ward, P. A., Harris, S., Mansfield, T., Cox, D. W.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency by restriction fragment length polymorphisms, and comparison with oligonucleotide probe analysis.</strong>
|
|
Lancet 328: 767-769, 1986. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2876232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2876232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2876232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(86)90297-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Hendrick1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hendrick, S. J., Silverman, A. K., Solomon, A. R., Headington, J. T.
|
|
<strong>Alpha-1-antitrypsin deficiency associated with panniculitis.</strong>
|
|
J. Am. Acad. Derm. 18: 684-692, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3259592" 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/s0190-9622(88)70091-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Hepper1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hepper, N. G., Black, L. F., Gleich, G. J., Kueppers, F.
|
|
<strong>The prevalence of alpha-1-antitrypsin deficiency in selected groups of patients with chronic obstructive lung disease.</strong>
|
|
Mayo Clin. Proc. 44: 697-710, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5344805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5344805</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5344805" 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="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="51" class="mim-anchor"></a>
|
|
<a id="Hodges1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hodges, J. R., Millward-Sadler, G. H., Barbatis, C., Wright, R.
|
|
<strong>Heterozygous MZ alpha-1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenic cirrhosis.</strong>
|
|
New Eng. J. Med. 304: 557-560, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6969850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6969850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6969850" 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/NEJM198103053041001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" 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="53" class="mim-anchor"></a>
|
|
<a id="Jeppsson1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jeppsson, J.-O., Larsson, C., Eriksson, S.
|
|
<strong>Characterization of alpha-1-antitrypsin in the inclusion bodies from the liver in alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 293: 576-579, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/168490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">168490</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=168490" 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/NEJM197509182931203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" 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="55" class="mim-anchor"></a>
|
|
<a id="Kay1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kay, M. A., Baley, P., Rothenberg, S., Leland, F., Fleming, L., Ponder, K. P., Liu, T., Finegold, M., Darlington, G., Pokorny, W., Woo, S. L. C.
|
|
<strong>Expression of human alpha-1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 89-93, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1729724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1729724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1729724" 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.89.1.89" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Kennedy1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kennedy, M., Brett, W.
|
|
<strong>Monozygotic twins with alpha-1-antitrypsin deficiency. (Letter)</strong>
|
|
Lancet 326: 527-528, 1985. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2857896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2857896</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2857896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(85)92133-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Kew1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kew, M. C., Turnbull, R., Prinsloo, I.
|
|
<strong>Alpha-1-antitrypsin deficiency and hepatocellular cancer.</strong>
|
|
Brit. J. Cancer 37: 635-638, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/206274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">206274</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=206274" 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/bjc.1978.93" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Kidd1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kidd, V. J., Golbus, M. S., Wallace, R. B., Itakura, K., Woo, S. L. C.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency by direct analysis of the mutation site in the gene.</strong>
|
|
New Eng. J. Med. 310: 639-642, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6607413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6607413</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6607413" 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/NEJM198403083101007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Kidd1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kidd, V. J., Wallace, R. B., Itakura, K., Woo, S. L. C.
|
|
<strong>Alpha-1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.</strong>
|
|
Nature 304: 230-234, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6306478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6306478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6306478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/304230a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Klasen1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klasen, E. C., Biemond, I., Laros, C. D.
|
|
<strong>Alpha-1-antitrypsin deficiency and the flaccid lung syndrome: the heterozygote controversy.</strong>
|
|
Clin. Genet. 29: 211-215, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3486059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3486059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3486059" 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="61" 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="62" class="mim-anchor"></a>
|
|
<a id="Kueppers1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kueppers, F., Fallat, R., Larson, R. K.
|
|
<strong>Obstructive lung diseases and alpha-antitrypsin deficiency gene heterozygosity.</strong>
|
|
Science 165: 899-901, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5816326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5816326</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5816326" 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.165.3896.899" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Kuhlenschmidt1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kuhlenschmidt, M. S., Yunis, E. J., Iammarino, R. M., Turco, S. J., Peters, S. P., Glew, R. H.
|
|
<strong>Demonstration of sialyltransferase deficiency in the serum of a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis.</strong>
|
|
Lab. Invest. 31: 413-419, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4547176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4547176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4547176" 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="Lake-Bakaar1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lake-Bakaar, G., Dooley, J. S.
|
|
<strong>Alpha-1-antitrypsin deficiency and liver disease. (Letter)</strong>
|
|
Lancet 320: 159 only, 1982. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6123870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6123870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6123870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(82)91127-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Langley1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Langley, C. E., Berninger, R. W., Wolfson, S. L., Talamo, R. C.
|
|
<strong>An unusual type of alpha-1-antitrypsin deficiency in a child.</strong>
|
|
Johns Hopkins Med. J. 144: 161-165, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/312969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">312969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=312969" 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="66" class="mim-anchor"></a>
|
|
<a id="Laurell1963" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laurell, C.-B., Eriksson, S.
|
|
<strong>The electrophoretic alpha-1-globulin pattern of serum in alpha-1-antitrypsin deficiency.</strong>
|
|
Scand. J. Clin. Lab. Invest. 15: 132-140, 1963.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Lazarin2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S.
|
|
<strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong>
|
|
Genet. Med. 15: 178-186, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22975760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22975760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22975760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/gim.2012.114" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Lemarchand1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lemarchand, P., Jaffe, H. A., Danel, C., Cid, M. C., Kleinman, H. K., Stratford-Perricaudet, L. D., Perricaudet, M., Pavirani, A., Lecocq, J.-P., Crystal, R. G.
|
|
<strong>Adenovirus-mediated transfer of a recombinant human alpha-1-antitrypsin cDNA to human endothelial cells.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 6482-6486, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631146</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631146" 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.89.14.6482" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" 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="70" 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="71" class="mim-anchor"></a>
|
|
<a id="Lieberman1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lieberman, J., Mittman, C., Kent, J. R.
|
|
<strong>Screening for heterozygous alpha-1-antitrypsin deficiency. III. A provocative test with diethylstilbestrol and effect of oral contraceptives.</strong>
|
|
JAMA 217: 1198-1206, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5109458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5109458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5109458" 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.217.9.1198" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Lieberman1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lieberman, J.
|
|
<strong>Heterozygous and homozygous alpha-1-antitrypsin deficiency in patients with pulmonary emphysema.</strong>
|
|
New Eng. J. Med. 281: 279-284, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4183173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4183173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4183173" 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/NEJM196908072810601" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Lomas1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lomas, D. A., Evans, D. L., Finch, J. T., Carrell, R. W.
|
|
<strong>The mechanism of Z alpha-1-antitrypsin accumulation in the liver.</strong>
|
|
Nature 357: 605-607, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1608473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1608473</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1608473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/357605a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Lomas1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lomas, D. A.
|
|
<strong>New insights into the structural basis of alpha-1-antitrypsin deficiency.</strong>
|
|
Quart. J. Med. 89: 807-812, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8977959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8977959</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8977959" 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/qjmed/89.11.807" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" 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="76" 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="77" class="mim-anchor"></a>
|
|
<a id="Meisen1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meisen, C., Higuchi, M., Brautigam, S., Driesel, A. J., Blandfort, M., Olek, K.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency using oligonucleotide probe analysis.</strong>
|
|
Hum. Genet. 79: 190-192, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2899055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2899055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2899055" 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/BF00280565" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Morin1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morin, T., Martin, J.-P., Feldmann, G., Rueff, B., Benhamou, J.-P., Ropartz, C.
|
|
<strong>Heterozygous alpha (1)-antitrypsin deficiency and cirrhosis in adults, a fortuitous association.</strong>
|
|
Lancet 305: 250-251, 1975. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/46389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">46389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=46389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(75)91143-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Morse1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morse, J. O.
|
|
<strong>Alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 299: 1045-1048 and 1099-1105, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/360063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">360063</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=360063" 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/NEJM197811092991905" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Neumann1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Neumann, F., Meirom, R., Rattner, D., Trainin, Z., Klopfer, U., Nobel, T. A.
|
|
<strong>Animal model of human disease: alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Path. 84: 427-430, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/133618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">133618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=133618" 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="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="82" 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="83" 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="84" 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="85" 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="86" class="mim-anchor"></a>
|
|
<a id="Perrault1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Perrault, J. L., Malo, J.-L., Bake, B., Renzi, G., Grassino, A.
|
|
<strong>Alpha-1-antitrypsin deficiency: genetic, clinical and functional correlations in a three generation family.</strong>
|
|
Respiration 37: 291-300, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/314139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">314139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=314139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000194041" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Pierce1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pierce, J. A., Eisen, A. Z., Dhingra, H. K.
|
|
<strong>Relationship of antitrypsin deficiency to the pathogenesis of emphysema.</strong>
|
|
Trans. Assoc. Am. Phys. 82: 87-97, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5310288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5310288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5310288" 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="88" class="mim-anchor"></a>
|
|
<a id="Rodriguez-Cintron1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rodriguez-Cintron, W., Guntupalli, K., Fraire, A. E.
|
|
<strong>Bronchiectasis and homozygous (PiZZ) alpha1-antitrypsin deficiency in a young man.</strong>
|
|
Thorax 50: 424-425, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7785020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7785020</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7785020" 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/thx.50.4.424" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Rodriguez-Soriano1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rodriguez-Soriano, J., Fidalgo, I., Camarero, C., Vallo, A., Oliveros, R.
|
|
<strong>Juvenile cirrhosis and membranous glomerulonephritis in a child with alpha-1-antitrypsin deficiency PiSZ.</strong>
|
|
Acta Paediat. Scand. 67: 793-796, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/309702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">309702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=309702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1651-2227.1978.tb16263.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Rosenthal1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenthal, P., Liebman, W. M., Thaler, M. M.
|
|
<strong>Alpha-1-antitrypsin deficiency and severe infantile liver disease.</strong>
|
|
Am. J. Dis. Child. 133: 1195-1196, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/315706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">315706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=315706" 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/archpedi.1979.02130110103023" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" 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="92" class="mim-anchor"></a>
|
|
<a id="Schmitt1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schmitt, M. G., Jr., Phillips, R. B., Matzen, R. N., Rodey, G.
|
|
<strong>Alpha-1-antitrypsin deficiency: a study of the relationship between the Pi system and genetic markers.</strong>
|
|
Am. J. Hum. Genet. 27: 315-321, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/830072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">830072</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=830072" 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="93" 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="94" class="mim-anchor"></a>
|
|
<a id="Sharp1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sharp, H. L., Bridges, R. A., Krivit, W., Freier, E. F.
|
|
<strong>Cirrhosis associated with alpha-1-antitrypsin deficiency: a previously unrecognized inherited disorder.</strong>
|
|
J. Lab. Clin. Med. 73: 934-939, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4182334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4182334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4182334" 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="95" class="mim-anchor"></a>
|
|
<a id="Sigsgaard1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sigsgaard, T., Brandslund, I., Rasmussen, J. B., Lund, E. D., Varming, H.
|
|
<strong>Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.</strong>
|
|
Pharmacogenetics 4: 135-141, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7920693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7920693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7920693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00008571-199406000-00004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Sigsgaard1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sigsgaard, T., Pedersen, O. F., Juul, S., Gravesen, S.
|
|
<strong>Respiratory disorders and atopy in cotton, wool and other textile mill workers in Denmark.</strong>
|
|
Am. J. Ind. Med. 22: 163-184, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415284</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415284" 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/ajim.4700220204" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Song1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Song, S., Morgan, M., Ellis, T., Poirier, A., Chesnut, K., Wang, J., Brantly, M., Muzyczka, N., Byrne, B. J., Atkinson, M., Flotte, T. R.
|
|
<strong>Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 14384-14388, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9826709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9826709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9826709[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=9826709" 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.95.24.14384" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Starzl1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Starzl, T. E., Porter, K. A., Francavilla, A., Iwatsuki, S.
|
|
<strong>Reversal of hepatic alpha-1-antitrypsin deposition after portacaval shunt.</strong>
|
|
Lancet 322: 424-426, 1983. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6135912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6135912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6135912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(83)90390-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Stevens1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stevens, P. M., Hnilica, V., Johnson, P. C., Bell, R. L.
|
|
<strong>Pathophysiology of hereditary emphysema.</strong>
|
|
Ann. Intern. Med. 74: 672-680, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4104410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4104410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4104410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-74-5-672" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Stockley1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stockley, R. A.
|
|
<strong>Alpha-1-antitrypsin phenotypes in cor pulmonale due to chronic obstructive airways disease.</strong>
|
|
Quart. J. Med. 48: 419-428, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/317359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">317359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=317359" 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="101" class="mim-anchor"></a>
|
|
<a id="Talamo1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Talamo, R. C., Allen, J. D., Kahan, M. G., Austen, K. F.
|
|
<strong>Hereditary alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 278: 345-351, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4169707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4169707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4169707" 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/NEJM196802152780701" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Talamo1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Talamo, R. C., Feingold, M.
|
|
<strong>Infantile cirrhosis with hereditary alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Dis. Child. 125: 845-849, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4196606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4196606</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4196606" 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/archpedi.1973.04160060051011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Tarkoff1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tarkoff, M. P., Kueppers, F., Miller, W. F.
|
|
<strong>Pulmonary emphysema and alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Med. 45: 220-228, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5666650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5666650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5666650" 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(68)90040-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Townley1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Townley, R. G., Ryning, F., Lynch, H. T., Brody, A. W.
|
|
<strong>Obstructive lung disease in hereditary alpha-1-antitrypsin deficiency.</strong>
|
|
JAMA 214: 325-331, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5469071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5469071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5469071" 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="105" class="mim-anchor"></a>
|
|
<a id="Udall1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Udall, J. N., Bloch, K. J., Walker, W. A.
|
|
<strong>Transport of proteases across neonatal intestine and development of liver disease in infants with alpha-1-antitrypsin deficiency.</strong>
|
|
Lancet 319: 1441-1443, 1982. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6123724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6123724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6123724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(82)92454-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Weber1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weber, W., Weidinger, S.
|
|
<strong>PI S-Cologne: a new variant in the alpha-1-antitrypsin system.</strong>
|
|
Hum. Genet. 80: 102, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262085</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3262085" 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/BF00451468" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Weitz1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weitz, J. I., Silverman, E. K., Thong, B., Campbell, E. J.
|
|
<strong>Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype: evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha-1-proteinase inhibitor.</strong>
|
|
J. Clin. Invest. 89: 766-773, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1541671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1541671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1541671" 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/JCI115654" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="108" class="mim-anchor"></a>
|
|
<a id="Wewers1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wewers, M. D., Casolaro, A., Sellers, S., Swayze, S. C., McPhaul, K. M., Wittes, J. T., Crystal, R. G.
|
|
<strong>Replacement therapy for alpha-1-antitrypsin deficiency associated with emphysema.</strong>
|
|
New Eng. J. Med. 316: 1055-1062, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3494198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3494198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3494198" 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/NEJM198704233161704" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Wiebicke1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wiebicke, W., Niggemann, B., Fischer, A.
|
|
<strong>Pulmonary function in children with homozygous alpha-1-protease inhibitor deficiency.</strong>
|
|
Europ. J. Pediat. 155: 603-607, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8831086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8831086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8831086" 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/BF01957913" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="110" class="mim-anchor"></a>
|
|
<a id="Wilcke1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilcke, J. T. R., Seersholm, N., Kok-Jensen, A., Dirksen, A.
|
|
<strong>Transmitting genetic risk information in families: attitudes about disclosing the identity of relatives.</strong>
|
|
Am. J. Hum. Genet. 65: 902-909, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302531" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Wu1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, Y., Whitman, I., Molmenti, E., Moore, K., Hippenmeyer, P., Perlmutter, D. H.
|
|
<strong>A lag in intracellular degradation of mutant alpha-1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha-1-antitrypsin deficiency.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 9014-9018, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8090762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8090762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8090762" 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.91.19.9014" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Yusa2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yusa, K., Rashid, S. T., Strick-Marchand, H., Varela, I., Liu, P.-Q., Paschon, D. E., Miranda, E., Ordonez, A., Hannan, N. R. F., Rouhani, F. J., Darche, S., Alexander, G., Marciniak, S. J., Fusaki, N., Hasegawa, M., Holmes, M. C., Di Santo, J. P., Lomas, D. A., Bradley, A., Vallier, L.
|
|
<strong>Targeted gene correction of alpha-1-antitrypsin deficiency in induced pluripotent stem cells.</strong>
|
|
Nature 478: 391-394, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21993621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21993621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21993621[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=21993621" 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/nature10424" 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">
|
|
Anne M. Stumpf - updated : 4/18/2013
|
|
</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">
|
|
Ada Hamosh - updated : 11/29/2011<br>Ada Hamosh - updated : 8/17/2010
|
|
</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">
|
|
Carol A. Bocchini : 7/20/2010
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 10/24/2024
|
|
</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 : 10/23/2024<br>carol : 03/22/2022<br>carol : 09/19/2019<br>carol : 09/18/2019<br>carol : 08/04/2016<br>carol : 07/09/2016<br>carol : 7/9/2016<br>carol : 2/10/2016<br>joanna : 2/9/2016<br>alopez : 4/18/2013<br>terry : 8/8/2012<br>alopez : 12/1/2011<br>terry : 11/29/2011<br>terry : 9/1/2010<br>alopez : 8/18/2010<br>terry : 8/17/2010<br>carol : 8/13/2010<br>carol : 8/13/2010
|
|
</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> 613490
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ALPHA-1-ANTITRYPSIN DEFICIENCY; A1ATD
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 30188007;
|
|
|
|
|
|
<strong>ICD10CM:</strong> E88.01;
|
|
|
|
|
|
<strong>ICD9CM:</strong> 273.4;
|
|
|
|
|
|
<strong>ORPHA:</strong> 178396, 60;
|
|
|
|
|
|
<strong>DO:</strong> 13372;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
14q32.13
|
|
</span>
|
|
</td>
|
|
<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>
|
|
<td>
|
|
<span class="mim-font">
|
|
SERPINA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
107400
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<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>
|
|
<td>
|
|
<span class="mim-font">
|
|
SERPINA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
107400
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
14q32.13
|
|
</span>
|
|
</td>
|
|
<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>
|
|
<td>
|
|
<span class="mim-font">
|
|
SERPINA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
107400
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because alpha-1-antitrypsin deficiency (A1ATD) is caused by mutation in the SERPINA1 gene (107400), most often by homozygosity for the PiZ allele (107400.0011).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Alpha-1-antitrypsin deficiency (A1ATD) is an autosomal recessive disorder. The most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age (Crystal, 1990). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Laurell and Eriksson (1963) described absence of alpha-1-antitrypsin from the plasma in patients with degenerative lung disease leading to death in middle life. Emphysematous changes involve primarily the lower lung fields (Bell, 1970). </p><p>Gans et al. (1969) described familial infantile liver cirrhosis in presumed homozygotes for alpha-1-antitrypsin deficiency. </p><p>An adult with antitrypsin deficiency and combined liver and lung disease was reported by Gherardi (1971). See the study of 12 cases of combined disease by Berg and Eriksson (1972). </p><p>Aagenaes et al. (1972) described the clinical picture in children with severe AAT deficiency (ZZ genotype) as neonatal cholestasis. Five such cases were described. </p><p>Fargion et al. (1981) found an increased frequency of non-M phenotypes in patients with hepatocellular carcinoma. Furthermore, patients with liver cancer and a non-M phenotype had a lower average age than those with an M phenotype. </p><p>Cox and Smyth (1983) found a relatively high risk for liver disease in men between 51 and 60 years who had AAT deficiency. A low concentration of serum prealbumin was a sensitive indicator of impaired liver function. </p><p>Eriksson et al. (1986) concluded that the risk of cirrhosis and liver cancer is increased for males homozygous for alpha-1-antitrypsin deficiency but not for females. The finding suggested additive effects of exogenous factors. </p><p>Wiebicke et al. (1996) confirmed the absence of pulmonary function abnormalities in the vast majority of children with severe (homozygous ZZ) AAT deficiency. </p><p>Rodriguez-Cintron et al. (1995) suggested that bronchiectasis should be considered part of the spectrum of pulmonary pathology that may be encountered in individuals with AAT deficiency. They described a 21-year-old man with massive hemoptysis and severe (homozygous ZZ) AAT deficiency. Neither panlobular emphysema nor cirrhosis of the liver was present. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Morin et al. (1975) concluded that heterozygotes are not at increased risk of alcoholic cirrhosis. </p><p>Geddes et al. (1977) found that the frequency of non-M AAT phenotypes was increased to a significant extent in patients with sclerosing alveolitis with or without rheumatoid arthritis. </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>Hendrick et al. (1988) described 3 patients in whom panniculitis was the presenting manifestation of AAT deficiency. Two were young adults and 1 was a child. The panniculitis in these cases is frequently, although not always, precipitated by trauma. The panniculitis is chronic, relapsing, and widely disseminated with new lesions appearing as old lesions resolve. </p><p>Fortin et al. (1991) reported a third incidence of systemic vasculitis associated with the ZZ genotype, which took the form of polyarteritis nodosa. </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 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. 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kidd et al. (1983) used a chemically synthesized specific oligonucleotide probe (19-mer) as a sensitive and direct test for the presence or absence of the Z allele (E342K; 107400.0011). Kidd et al. (1984) reported the use of such probes in the prenatal diagnosis of the deficiency syndrome. </p><p>Hejtmancik et al. (1986) compared prenatal diagnosis by RFLP analysis with prenatal diagnosis by oligonucleotide probe analysis. They concluded that although it seems reasonable to use oligonucleotide analysis in families in which no sibs are available for comparison, in all other situations RFLP analysis is preferable because it is as accurate and reliable as oligonucleotide analysis and is technically easier. </p><p>Abbott et al. (1988) used the PCR for prenatal diagnosis of alpha-1-antitrypsin deficiency associated with the ZZ genotype. </p><p>To identify accurately the SZ phenotype at the DNA level, Nukiwa et al. (1986) prepared 19-mer synthetic oligonucleotide probes: 2 to show the M/S difference in exon 3, and 2 to show the M/Z difference in exon 5. </p><p>Harrison et al. (1990) described an improved method for detecting what they termed 'low Z expressor' phenotype in MZ heterozygotes. An obligate carrier mother who was being typed as part of a family study appeared to be a PI(M)/PI(null) heterozygote. By routine isoelectric focusing, she was typed as M, her affected child as Z, and her husband as MZ. Atypically low concentrations of circulating Z peptides were demonstrated by the improved method. </p><p>Dry (1991) described a method for detecting the single-base substitution in PiZ useful for same-day diagnosis of AAT deficiency in chorion villus samples. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Udall et al. (1982) speculated that a factor in the pathogenesis of infantile cirrhosis may be lack of protease inhibitor to counteract the effects of proteases that cross the intestinal barrier in the neonate. Lake-Bakaar and Dooley (1982) found that alpha-1-antitrypsin is an important proteolytic inhibitor in bile, thus providing support of the pathogenetic theory of Udall et al. (1982). </p><p>Weitz et al. (1992) demonstrated a correlation between plasma levels of elastase-specific fibrinopeptides and PI genotype. The levels of these peptides were highest in ZZ homozygotes and intermediate in MZ heterozygotes. This was interpreted as evidence that unopposed human neutrophil elastase (ELA2; 130130) is responsible for emphysema in patients with alpha-1-proteinase inhibitor deficiency. </p><p>Lomas et al. (1992) presented an explanation for the accumulation of insoluble intracellular inclusions in the ZZ homozygote. Only about 15% of the AAT protein is secreted in the plasma in ZZ homozygotes. The 85% that is not secreted accumulates in the endoplasmic reticulum (ER) of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. About 10% of newborn ZZ homozygotes develop liver disease that often leads to fatal childhood cirrhosis. Lomas et al. (1992) demonstrated the molecular pathology underlying this accumulation and described how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive center loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. The loop-sheet polymerization is concentration- and temperature-dependent. At times of stress, the formation of inclusions in the hepatocyte will likely overwhelm the degradative mechanisms. Antitrypsin is an acute phase protein and as such undergoes a manifold increase in association with temperature elevations during bouts of inflammation. Control of inflammation and pyrexia in ZZ homozygote infants is important. In the long-term, more specific interventions may be possible, e.g., the delivery to the hepatocyte of engineered loop peptides specific to alpha-1-antitrypsin. </p><p>Liver injury in individuals with the ZZ genotype presumably results from toxic effects of the abnormal AAT molecule accumulating within the endoplasmic reticulum of liver cells; however, only 12 to 15% of individuals with this genotype develop liver disease. Therefore, Wu et al. (1994) predicted that other genetic factors determine susceptibility to liver disease. To examine this hypothesis, they transduced skin fibroblasts from ZZ individuals with liver disease and from ZZ individuals without liver disease with amphotropic recombinant retroviral particles designed to express the mutant AAT*Z gene under direction of a constitutive viral promoter. Expression of the AAT gene was conferred on each fibroblast cell line. Compared to the same cell line transduced with the wildtype gene, there was selective intracellular accumulation of the mutant protein in each case. However, there was a marked delay in degradation of the mutant protein after it accumulated in the fibroblasts from ZZ individuals with liver disease ('susceptible hosts') as compared to those without liver disease ('protected hosts'). Appropriate disease controls showed that the lag in degradation in susceptible hosts is specific for the combination of the ZZ genotype and liver disease. Biochemical characteristics of the ATT*Z degradation in the protected hosts was found to be similar to those of a common ER degradation pathway previously described for T-cell receptor alpha subunits and asialoglycoprotein receptor subunits, therefore raising the possibility that the lag in degradation in the susceptible host is a defect in this common ER degradation pathway. </p><p>As reviewed by Lomas (1996), inclusions in the most frequent cause of antitrypsin deficiency, the Z mutation (glu342lys; 107400.0011), is accompanied by accumulation of protein in the endoplasmic reticulum of the liver. These hepatic inclusions in turn result from a protein-protein interaction between the reactive center loop of 1 molecule and the beta-pleated sheet of a second. This loop-sheet polymerization is the basis of deficiencies associated also with mutations of C1-inhibitor (606860), antithrombin III (107300), and alpha-1-antichymotrypsin (107280), all of which are serine proteinase inhibitors (serpins). </p><p>Sigsgaard et al. (1992) showed that in cotton workers the airborne concentration of respirable endotoxin was associated with byssinosis. Endotoxin might induce byssinosis through the release of biochemical mediators at the bronchoalveolar surface. Alpha-1-antitrypsin, which neutralizes enzymes released by granulocytes, might have a counteracting role. Sigsgaard et al. (1994) found that the MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM phenotype: 3/8 (38%) and 25/187 (13%). An association between the MZ phenotype and familial allergy was also found, although the association was somewhat weaker. </p><p>Carrell and Lomas (2002) suggested that alpha-1-antitrypsin deficiency is a model for conformational diseases. These are disorders due to aberrant intermolecular aggregation of proteins. Furthermore, alpha-1-antitrypsin deficiency provides a prototype for the diseases associated with abnormalities of various serpins, known collectively as the serpinopathies. Knowledge of the shared underlying conformational mechanism of protein deposition in neuronal tissues greatly increased understanding of what had previously been a daunting collection of syndromes of neurodegeneration. These included encephalopathy with neuroserpin inclusion bodies (604218), the Lewy-body variant of Alzheimer disease (see 127750) with deposits of alpha-synuclein (163890), prion protein (176640) deposition in Creutzfeldt-Jakob disease (123400), tau protein associated with Pick bodies of frontotemporal dementia (Pick disease; 172700), and the inclusions of huntingtin (613004) in Huntington disease (143100). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Wewers et al. (1987) reported on treatment of patients with alpha-1-antitrypsin deficiency with intravenous plasma-derived AAT once a week. Although granting that a completely rigorous study was impossible, the authors concluded that infusions of AAT are safe and can reverse the biochemical abnormalities in serum and lung fluid and, further, that lifetime avoidance of cigarette smoking together with such replacement may be a logical approach to long-term therapy. </p><p>George et al. (1984) tested the effectiveness of a genetically engineered met358-to-val mutant in the reactive center of AAT as an inhibitor of connective tissue breakdown in a model of inflammation. Degradation of basement membrane collagen was efficiently inhibited by a concentration of the mutant substance that was tenfold lower than that of the normal antitrypsin. George et al. (1984) suggested the possible use of this mutant in the prophylaxis of lung dysplasias, notably emphysema. </p><p>The liver represents an excellent organ for gene therapy since many genetic disorders result from deficiency of liver-specific gene products. Kay et al. (1992) demonstrated the autologous transplantation of canine hepatocytes transduced with a retroviral vector containing the human alpha-1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. At least 1 billion hepatocytes or 5% of the liver mass could be transplanted by the portal vasculature. Human alpha-1-antitrypsin was demonstrable in the serum of 2 dogs for 1 month. Although the serum levels of human AAT eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of the transduced hepatocytes migrated to the liver and continued to survive in vivo. </p><p>As a model for gene therapy, Garver et al. (1987) used a retroviral vector to insert human alpha-1-antitrypsin cDNA into the genome of mouse fibroblasts. After demonstrating that the clone produced human antitrypsin after more than 100 population doublings in the absence of selection pressure, they transplanted the clone into the peritoneal cavities of nude mice. When the animals were evaluated 4 weeks later, human antitrypsin was detected in both sera and the epithelial surface of the lungs. Lemarchand et al. (1992) reported experiments supporting the feasibility of in vivo human gene transfer of recombinant human AAT cDNA to endothelial cells by means of replication-deficiency adenovirus vectors. </p><p>Song et al. (1998) described experiments in mice in which recombinant adeno-associated virus (AAV) vectors were used to transduce skeletal muscle as a platform for secretion of alpha-1-antitrypsin and other therapeutic proteins. The utility of this approach for treating AAT deficiency was tested in murine myocytes in vitro and in vivo. Serum concentrations were 100,000-fold higher than those previously observed with AAV vectors in muscle and at levels that would be therapeutic if achieved in humans. High-level expression was delayed for several weeks but was sustained for over 15 weeks. Immune responses were dependent upon the mouse strain and the vector dosage. These data suggested that recombinant AAV vector transduction of skeletal muscle could provide a means for replacing AAT or other essential serum proteins but that immune responses may be elicited under certain conditions. </p><p>Wilcke et al. (1999) examined attitudes about disclosing the identities of family members to a physician to ensure diffusion of genetic risk information within affected families, by means of a questionnaire study of Danish patients with alpha-1-antitrypsin deficiency (symbolized A1AD), their relatives, and a control group of Danish citizens. Only 2.8% objected to disclosing the identity of children, 9.1% objected to disclosing the identity of parents, and 6.7% objected to disclosing the identity of sibs. When genetic tests were offered to a sister, 75.4% of screened individuals with severe A1AD (phenotype 'piZ') and 66.8% of piZ probands thought that the physician should say who was ill. Important reasons for informing a sister at risk were, for 58%, the opportunity to prevent disease and, for 41% of piZ-probands, the opportunity to maintain openness in the family and to avoid uncertainty. The women were less prone to disclose the identity of sibs. Wilcke et al. (1999) concluded that the genetic counselor should ensure that relatives are properly informed about their risk of a severe genetic disorder, such as A1AD, in which disability can be prevented by change of lifestyle or by careful management. Because of a certain amount of ambivalence encountered in affected families, they recognized the necessity to exercise flexibility and responsiveness to individual circumstances when asking for relatives' identity and when approaching relatives. </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 is 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 of 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, and also provided a proof of principle for therapeutic use of autophagy enhancers. </p><p>Yusa et al. (2011) showed that a combination of zinc finger nucleases and piggyBac technology in human induced pluripotent stem cells (iPSCs) can achieve biallelic correction of a point mutation (glu342 to lys; 107400.0011) in the alpha-1-antitrypsin gene that is responsible for alpha-1-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of alpha-1-antitrypsin in subsequently derived liver cells in vitro and in vivo. Yusa et al. (2011) stated that this approach was significantly more efficient than any other gene-targeting technology then available and crucially prevented contamination of the host genome with residual nonhuman sequences. The authors concluded that their results provided the first proof of principle for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Family studies indicated recessive inheritance of antitrypsin deficiency.</p><p>In early studies, heterozygotes, who can be detected chemically, were unaffected clinically; later studies suggested that heterozygosity may predispose to lung disease (Lieberman, 1969). For example, of 12 patients with obstructive lung disease present before age 40 years, 2 were judged by Tarkoff et al. (1968) to be homozygous for the deficiency and 1 heterozygous. Among 103 patients, Kueppers et al. (1969) found 5 homozygotes and 25 heterozygotes for the deficiency gene. They suggested that, especially in males, heterozygosity may predispose to chronic obstructive lung disease. Stevens et al. (1971) concluded that heterozygotes may develop emphysema qualitatively like that in homozygotes, but at a later age. The importance of prompt treatment of respiratory infections and avoidance of proteolytic aerosols, smoking and employment entailing exposure to respiratory irritants are important preventive measures in these families. </p><p>To study the question of the role of alpha-1-antitrypsin heterozygosity in the etiopathogenesis of chronic obstructive pulmonary disease (COPD) and to obviate the difficulties of precise diagnosis, Klasen et al. (1986) used a well-defined subgroup suffering from so-called 'flaccid lung.' In these persons, there is a loss of elasticity of the lung parenchyma with high compliance. Flaccid lung can be found with a high vital capacity, with spontaneous pneumothorax, in patients with giant bullae, and in all patients with lung emphysema. Klasen et al. (1986) found a relative risk of 12.5 for PI ZZ persons and 1.8 for MZ persons. They concluded that the risk of MZ persons compared to MM persons is almost negligible and that whether the MZ person develops lung disease is probably highly influenced by environmental and perhaps other genetic factors. </p><p>Dahl et al. (2002) reported on a study in Copenhagen to determine whether the MZ intermediate alpha-1-antitrypsin deficiency affects pulmonary function and disease. They randomly selected 9,187 adults from the Danish general population and followed them over a 21-year period; 451 (4.9%) carried the MZ genotype. Plasma antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype. They found that MZ heterozygotes had a slightly greater rate of decrease in FEV1 measure of pulmonary function and were modestly overrepresented among persons with airway obstruction and chronic obstructive pulmonary disease (COPD; 606963). They estimated that in the population at large, MZ heterozygosity may account for a fraction of COPD cases (on the order of 2%), similar to the percentage of persons with COPD who have the severe but rare ZZ genotype. Because the incidence of heterozygosity is so much higher than that of homozygosity, alpha-1-antitrypsin heterozygosity is as important a public health problem as homozygosity. </p><p>From study of 60-year-old twins with ZZ alpha-1-antitrypsin deficiency, one a heavy smoker who developed severe emphysema and the other a lifelong nonsmoker who was asymptomatic with only mild evidence of obstructive pulmonary disease, Kennedy and Brett (1985) demonstrated the importance of the environmental factor. A brother died at age 40 years of emphysema. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<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>Alpha-1-antitrypsin deficiency is said to be rare among Japanese. 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>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 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><p>On the basis of data from previously published genetic epidemiologic studies, de Serres et al. (2003) estimated the frequency of AAT deficiency in France, Italy, Portugal, and Spain. In another report, de Serres et al. (2003) focused on the distribution of the PiS and PiZ deficiency alleles in Australia, Canada, New Zealand, and the United States. </p><p>Among 15,484 ethnically diverse individuals screened for alpha-1 antitrypsin deficiency carrier status, Lazarin et al. (2013) identified 1,178 carriers (7.6%), for an estimated carrier frequency of approximately 1 in 13. Forty-seven 'carrier couples' were identified. Thirty-eight individuals were identified as homozygotes or compound heterozygotes. Among 8,570 individuals of northern European origin, Lazarin et al. (2013) identified a carrier frequency of 1 in 10. Among 747 individuals of east Asian origin, the carrier frequency was 1 in 249. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Deficiency of protease inhibitor activity is associated with several of the electrophoretic variants of serum alpha-1-antitrypsin; Axelsson and Laurell (1965) first suggested that the genes for electrophoretic variants are allelic with the deficiency 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>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>By means of isoelectric focusing, Weber and Weidinger (1988) found a PI variant that they called PI S (Cologne). A father and daughter were heterozygous. Alpha-1-antitrypsin concentrations were within the normal range. </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>Bamforth and Kalsheker (1988) discussed a rare Pi null allele that in homozygous state leads to pulmonary emphysema at an early age. In 3 families, all the affected individuals presented in early childhood with recurrent chest infections and wheezing, presumably related to passive smoking. Even though there was no detectable AAT, no partial or complete deletion of the gene could be identified. </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 (M358R; 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 and 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>
|
|
The most widely recognized candidate gene in COPD (see 606963) 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><p><strong><em>Reviews</em></strong></p><p>
|
|
Crystal (1990) gave a comprehensive review of the pathogenetic relationship between AAT deficiency and emphysema and liver disease, including a detailed listing of the various mutations that have been identified and a discussion of the possibilities for therapy. </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 Siiyama 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Eriksson (1989) gave an interesting historical account including the pedigree of his first family (Eriksson, 1965). </p><p>Several reports (Bell and Carrell, 1973; Kuhlenschmidt et al., 1974; Eriksson and Larsson, 1975) had suggested that the defect may be in a sialyltransferase and that deficiency of antitrypsin in the blood is the result of impaired secretion from hepatocytes, increased clearance of the undersialated protein, or both. It is difficult to see how this could cause codominant inheritance or account for the different types that appear to be the products of at least 30 different alleles, unless an amino acid substitution interferes with sialidation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Arnaud et al. (1977); Chan et al. (1978); Cox (2001); Falk and
|
|
Briscoe (1970); Falk (1970); Freeman et al. (1976); Guenter et al.
|
|
(1971); Hall et al. (1976); Hepper et al. (1969); Hodges et al.
|
|
(1981); Jeppsson et al. (1975); Kew et al. (1978); Kueppers and Bearn
|
|
(1967); Langley et al. (1979); Lieberman et al. (1971); Long et al.
|
|
(1984); Meisen et al. (1988); Morse (1978); Neumann et al. (1976);
|
|
Nukiwa et al. (1986); Perrault et al. (1979); Pierce et al. (1969);
|
|
Rodriguez-Soriano et al. (1978); Rosenthal et al. (1979); Schmitt et
|
|
al. (1975); Sharp et al. (1969); Starzl et al. (1983); Stockley
|
|
(1979); Talamo et al. (1968); Talamo and Feingold (1973); Townley et
|
|
al. (1970)
|
|
</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">
|
|
Aagenaes, O., Matlary, A., Elgjo, K., Munthe, E., Fagerhol, M.
|
|
<strong>Neonatal cholestasis in alpha-1-antitrypsin deficient children: clinical, genetic, histological and immunohistochemical findings.</strong>
|
|
Acta Paediat. Scand. 61: 632-642, 1972.
|
|
|
|
|
|
[PubMed: 4117022]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1972.tb15960.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abbott, C. M., McMahon, C. J., Whitehouse, D. B., Povey, S.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency using polymerase chain reaction. (Letter)</strong>
|
|
Lancet 331: 763-764, 1988. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 2895285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(88)91565-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arnaud, P., Galbraith, R. M., Faulk, W. P.
|
|
<strong>Increased frequency of the MZ phenotype of alpha-1-protease inhibitor in juvenile chronic polyarthritis.</strong>
|
|
J. Clin. Invest. 60: 1442-1444, 1977.
|
|
|
|
|
|
[PubMed: 334801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI108906]
|
|
|
|
|
|
</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">
|
|
Bamforth, F. J., Kalsheker, N. A.
|
|
<strong>Alpha-1 antitrypsin deficiency due to Pi null: clinical presentation and evidence for molecular heterogeneity.</strong>
|
|
J. Med. Genet. 25: 83-87, 1988.
|
|
|
|
|
|
[PubMed: 2831367]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.25.2.83]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bell, O. F., Carrell, R. W.
|
|
<strong>Basis of the defect in alpha-1-antitrypsin deficiency.</strong>
|
|
Nature 243: 410-411, 1973.
|
|
|
|
|
|
[PubMed: 4542721]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/243410a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bell, R. S.
|
|
<strong>The radiographic manifestations of alpha-1 antitrypsin deficiency: an important recognizable pattern of chronic obstructive pulmonary disease (COPD).</strong>
|
|
Radiology 95: 19-24, 1970.
|
|
|
|
|
|
[PubMed: 5417042]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1148/95.1.19]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berg, N. O., Eriksson, S.
|
|
<strong>Liver disease in adults with alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 287: 1264-1267, 1972.
|
|
|
|
|
|
[PubMed: 4117996]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197212212872502]
|
|
|
|
|
|
</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">
|
|
Carrell, R. W., Lomas, D. A.
|
|
<strong>Alpha-1-antitrypsin deficiency--a model for conformational diseases.</strong>
|
|
New Eng. J. Med. 346: 45-53, 2002.
|
|
|
|
|
|
[PubMed: 11778003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMra010772]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, C. H., Steer, C. J., Vergalla, J., Jones, E. A.
|
|
<strong>Alpha-1-antitrypsin deficiency with cirrhosis associated with the protease inhibitor phenotype SZ.</strong>
|
|
Am. J. Med. 65: 978-986, 1978.
|
|
|
|
|
|
[PubMed: 217266]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(78)90750-7]
|
|
|
|
|
|
</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">
|
|
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., 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.
|
|
<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 (pub.) 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. 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">
|
|
Dahl, M., Tybjaerg-Hansen, A., Lange, P., Vestbo, J., Nordestgaard, B. G.
|
|
<strong>Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha-1-antitrypsin MZ heterozygotes: a longitudinal study of the general population.</strong>
|
|
Ann. Intern. Med. 136: 270-279, 2002.
|
|
|
|
|
|
[PubMed: 11848724]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-136-4-200202190-00006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Serres, F. J., Blanco, I., Fernandez-Bustillo, E.
|
|
<strong>Genetic epidemiology of alpha-1 antitrypsin deficiency in North America and Australia/New Zealand: Australia, Canada, New Zealand and the United States of America.</strong>
|
|
Clin. Genet. 64: 382-397, 2003.
|
|
|
|
|
|
[PubMed: 14616761]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00143.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Serres, F. J., Blanco, I., Fernandez-Bustillo, E.
|
|
<strong>Genetic epidemiology of alpha-1 antitrypsin deficiency in southern Europe: France, Italy, Portugal and Spain.</strong>
|
|
Clin. Genet. 63: 490-509, 2003.
|
|
|
|
|
|
[PubMed: 12786756]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00078.x]
|
|
|
|
|
|
</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">
|
|
Dry, P. J.
|
|
<strong>Rapid detection of alpha-1-antitrypsin deficiency by analysis of a PCR-induced TaqI restriction site.</strong>
|
|
Hum. Genet. 87: 742-744, 1991.
|
|
|
|
|
|
[PubMed: 1937480]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00201739]
|
|
|
|
|
|
</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">
|
|
Eriksson, S., Carlson, J., Velez, R.
|
|
<strong>Risk of cirrhosis and primary liver cancer in alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 314: 736-739, 1986.
|
|
|
|
|
|
[PubMed: 3485248]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198603203141202]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eriksson, S., Larsson, C.
|
|
<strong>Purification and partial characterization of PAS-positive inclusion bodies from the liver in alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 292: 176-180, 1975.
|
|
|
|
|
|
[PubMed: 45843]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197501232920403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eriksson, S.
|
|
<strong>Studies in alpha 1-antitrypsin deficiency.</strong>
|
|
Acta Med. Scand. Suppl. 432: 1-85, 1965.
|
|
|
|
|
|
[PubMed: 4160491]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eriksson, S.
|
|
<strong>Alpha-1-antitrypsin deficiency: lessons learned from the bedside to the gene and back again.</strong>
|
|
Chest 95: 181-189, 1989.
|
|
|
|
|
|
[PubMed: 2642407]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1378/chest.95.1.181]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Falk, G. A., Briscoe, W. A.
|
|
<strong>Alpha-1-antitrypsin deficiency in chronic obstructive pulmonary disease.</strong>
|
|
Ann. Intern. Med. 72: 427-429, 1970.
|
|
|
|
|
|
[PubMed: 4906114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-72-3-427]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Falk, G. A.
|
|
<strong>Chronic obstructive pulmonary disease and heterozygous alpha-1-antitrypsin deficiency. (Editorial)</strong>
|
|
Ann. Intern. Med. 72: 595-596, 1970.
|
|
|
|
|
|
[PubMed: 4191180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-72-4-595]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fargion, S., Klasen, E. C., Lalatta, F., Sangalli, G., Tommasini, M., Fiorelli, G.
|
|
<strong>Alpha-1-antitrypsin in patients with carcinoma and chronic active hepatitis.</strong>
|
|
Clin. Genet. 19: 134-139, 1981.
|
|
|
|
|
|
[PubMed: 6258829]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1981.tb00684.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fortin, P. R., Fraser, R. S., Watts, C. S., Esdaile, J. M.
|
|
<strong>Alpha-1 antitrypsin deficiency and systemic necrotizing vasculitis.</strong>
|
|
J. Rheum. 18: 1613-1616, 1991.
|
|
|
|
|
|
[PubMed: 1684994]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Freeman, H. J., Weinstein, W. M., Shnitka, T. K., Crockford, P. M., Herbert, F. A.
|
|
<strong>Alpha-1-antitrypsin deficiency and pancreatic fibrosis.</strong>
|
|
Ann. Intern. Med. 85: 73-76, 1976.
|
|
|
|
|
|
[PubMed: 1084722]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-85-1-73]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gans, H., Sharp, H. L., Tan, B. H.
|
|
<strong>Antiprotease deficiency and familial infantile liver cirrhosis.</strong>
|
|
Surg. Gynec. Obstet. 129: 289-299, 1969.
|
|
|
|
|
|
[PubMed: 4240153]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garver, R. I., Jr., Chytil, A., Courtney, M., Crystal, R. G.
|
|
<strong>Clonal gene therapy: transplanted mouse fibroblast clones express human alpha-1-antitrypsin gene in vivo.</strong>
|
|
Science 237: 762-764, 1987.
|
|
|
|
|
|
[PubMed: 3497452]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3497452]
|
|
|
|
|
|
</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">
|
|
Geddes, D. M., Webley, M., Brewerton, D. A., Turton, C. W., Turner-Warwick, M., Murphy, A. H., Ward, A. M.
|
|
<strong>Alpha-1-antitrypsin phenotypes in fibrosing alveolitis and rheumatoid arthritis.</strong>
|
|
Lancet 310: 1049-1051, 1977. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 72955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(77)91883-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
George, P. M., Vissers, M. C. M., Travis, J., Winterbourn, C. C., Carrell, R. W.
|
|
<strong>A genetically engineered mutant of alpha-1-antitrypsin protects connective tissue from neutrophil damage and may be useful in lung disease.</strong>
|
|
Lancet 324: 1426-1428, 1984. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 6151045]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(84)91623-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gherardi, G. J.
|
|
<strong>Alpha-1-antitrypsin deficiency and its effect on the liver.</strong>
|
|
Hum. Path. 2: 173-175, 1971.
|
|
|
|
|
|
[PubMed: 5095241]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0046-8177(71)80026-6]
|
|
|
|
|
|
</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">
|
|
Guenter, C. A., Welch, M. H., Hammarsten, J. F.
|
|
<strong>Alpha-1-antitrypsin deficiency and pulmonary emphysema.</strong>
|
|
Annu. Rev. Med. 22: 283-292, 1971.
|
|
|
|
|
|
[PubMed: 4944420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.me.22.020171.001435]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, W. J., Hyde, R. W., Schwartz, R. H., Mudholkar, G. S., Webb, D. R., Chaubey, Y. P., Townes, P. L.
|
|
<strong>Pulmonary abnormalities in intermediate alpha-1-antitrypsin deficiency.</strong>
|
|
J. Clin. Invest. 58: 1069-1077, 1976.
|
|
|
|
|
|
[PubMed: 1086856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI108558]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harrison, H. H., Miller, K. L., Whitington, P. F.
|
|
<strong>Improved detection, via ISO-DALT two-dimensional electrophoresis, of 'low Z expressor' individuals with alpha-1-antitrypsin MZ phenotype.</strong>
|
|
Clin. Chem. 36: 1850-1851, 1990.
|
|
|
|
|
|
[PubMed: 2208671]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hejtmancik, J. F., Sifers, R. N., Ward, P. A., Harris, S., Mansfield, T., Cox, D. W.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency by restriction fragment length polymorphisms, and comparison with oligonucleotide probe analysis.</strong>
|
|
Lancet 328: 767-769, 1986. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 2876232]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(86)90297-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hendrick, S. J., Silverman, A. K., Solomon, A. R., Headington, J. T.
|
|
<strong>Alpha-1-antitrypsin deficiency associated with panniculitis.</strong>
|
|
J. Am. Acad. Derm. 18: 684-692, 1988.
|
|
|
|
|
|
[PubMed: 3259592]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0190-9622(88)70091-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hepper, N. G., Black, L. F., Gleich, G. J., Kueppers, F.
|
|
<strong>The prevalence of alpha-1-antitrypsin deficiency in selected groups of patients with chronic obstructive lung disease.</strong>
|
|
Mayo Clin. Proc. 44: 697-710, 1969.
|
|
|
|
|
|
[PubMed: 5344805]
|
|
|
|
|
|
|
|
</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">
|
|
Hodges, J. R., Millward-Sadler, G. H., Barbatis, C., Wright, R.
|
|
<strong>Heterozygous MZ alpha-1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenic cirrhosis.</strong>
|
|
New Eng. J. Med. 304: 557-560, 1981.
|
|
|
|
|
|
[PubMed: 6969850]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198103053041001]
|
|
|
|
|
|
</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">
|
|
Jeppsson, J.-O., Larsson, C., Eriksson, S.
|
|
<strong>Characterization of alpha-1-antitrypsin in the inclusion bodies from the liver in alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 293: 576-579, 1975.
|
|
|
|
|
|
[PubMed: 168490]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197509182931203]
|
|
|
|
|
|
</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">
|
|
Kay, M. A., Baley, P., Rothenberg, S., Leland, F., Fleming, L., Ponder, K. P., Liu, T., Finegold, M., Darlington, G., Pokorny, W., Woo, S. L. C.
|
|
<strong>Expression of human alpha-1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 89-93, 1992.
|
|
|
|
|
|
[PubMed: 1729724]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.89.1.89]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kennedy, M., Brett, W.
|
|
<strong>Monozygotic twins with alpha-1-antitrypsin deficiency. (Letter)</strong>
|
|
Lancet 326: 527-528, 1985. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 2857896]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(85)92133-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kew, M. C., Turnbull, R., Prinsloo, I.
|
|
<strong>Alpha-1-antitrypsin deficiency and hepatocellular cancer.</strong>
|
|
Brit. J. Cancer 37: 635-638, 1978.
|
|
|
|
|
|
[PubMed: 206274]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/bjc.1978.93]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kidd, V. J., Golbus, M. S., Wallace, R. B., Itakura, K., Woo, S. L. C.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency by direct analysis of the mutation site in the gene.</strong>
|
|
New Eng. J. Med. 310: 639-642, 1984.
|
|
|
|
|
|
[PubMed: 6607413]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198403083101007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kidd, V. J., Wallace, R. B., Itakura, K., Woo, S. L. C.
|
|
<strong>Alpha-1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.</strong>
|
|
Nature 304: 230-234, 1983.
|
|
|
|
|
|
[PubMed: 6306478]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/304230a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klasen, E. C., Biemond, I., Laros, C. D.
|
|
<strong>Alpha-1-antitrypsin deficiency and the flaccid lung syndrome: the heterozygote controversy.</strong>
|
|
Clin. Genet. 29: 211-215, 1986.
|
|
|
|
|
|
[PubMed: 3486059]
|
|
|
|
|
|
|
|
</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., Fallat, R., Larson, R. K.
|
|
<strong>Obstructive lung diseases and alpha-antitrypsin deficiency gene heterozygosity.</strong>
|
|
Science 165: 899-901, 1969.
|
|
|
|
|
|
[PubMed: 5816326]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.165.3896.899]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kuhlenschmidt, M. S., Yunis, E. J., Iammarino, R. M., Turco, S. J., Peters, S. P., Glew, R. H.
|
|
<strong>Demonstration of sialyltransferase deficiency in the serum of a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis.</strong>
|
|
Lab. Invest. 31: 413-419, 1974.
|
|
|
|
|
|
[PubMed: 4547176]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lake-Bakaar, G., Dooley, J. S.
|
|
<strong>Alpha-1-antitrypsin deficiency and liver disease. (Letter)</strong>
|
|
Lancet 320: 159 only, 1982. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 6123870]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(82)91127-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Langley, C. E., Berninger, R. W., Wolfson, S. L., Talamo, R. C.
|
|
<strong>An unusual type of alpha-1-antitrypsin deficiency in a child.</strong>
|
|
Johns Hopkins Med. J. 144: 161-165, 1979.
|
|
|
|
|
|
[PubMed: 312969]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laurell, C.-B., Eriksson, S.
|
|
<strong>The electrophoretic alpha-1-globulin pattern of serum in alpha-1-antitrypsin deficiency.</strong>
|
|
Scand. J. Clin. Lab. Invest. 15: 132-140, 1963.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lazarin, G. A., Haque, I. S., Nazareth, S., Iori, K., Patterson, A. S., Jacobson, J. L., Marshall, J. R., Seltzer, W. K., Patrizio, P., Evans, E. A., Srinivasan, B. S.
|
|
<strong>An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.</strong>
|
|
Genet. Med. 15: 178-186, 2013.
|
|
|
|
|
|
[PubMed: 22975760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/gim.2012.114]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lemarchand, P., Jaffe, H. A., Danel, C., Cid, M. C., Kleinman, H. K., Stratford-Perricaudet, L. D., Perricaudet, M., Pavirani, A., Lecocq, J.-P., Crystal, R. G.
|
|
<strong>Adenovirus-mediated transfer of a recombinant human alpha-1-antitrypsin cDNA to human endothelial cells.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 6482-6486, 1992.
|
|
|
|
|
|
[PubMed: 1631146]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.89.14.6482]
|
|
|
|
|
|
</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">
|
|
Lieberman, J., Mittman, C., Kent, J. R.
|
|
<strong>Screening for heterozygous alpha-1-antitrypsin deficiency. III. A provocative test with diethylstilbestrol and effect of oral contraceptives.</strong>
|
|
JAMA 217: 1198-1206, 1971.
|
|
|
|
|
|
[PubMed: 5109458]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.217.9.1198]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lieberman, J.
|
|
<strong>Heterozygous and homozygous alpha-1-antitrypsin deficiency in patients with pulmonary emphysema.</strong>
|
|
New Eng. J. Med. 281: 279-284, 1969.
|
|
|
|
|
|
[PubMed: 4183173]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM196908072810601]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lomas, D. A., Evans, D. L., Finch, J. T., Carrell, R. W.
|
|
<strong>The mechanism of Z alpha-1-antitrypsin accumulation in the liver.</strong>
|
|
Nature 357: 605-607, 1992.
|
|
|
|
|
|
[PubMed: 1608473]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/357605a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lomas, D. A.
|
|
<strong>New insights into the structural basis of alpha-1-antitrypsin deficiency.</strong>
|
|
Quart. J. Med. 89: 807-812, 1996.
|
|
|
|
|
|
[PubMed: 8977959]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/qjmed/89.11.807]
|
|
|
|
|
|
</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">
|
|
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">
|
|
Meisen, C., Higuchi, M., Brautigam, S., Driesel, A. J., Blandfort, M., Olek, K.
|
|
<strong>Prenatal diagnosis of alpha-1-antitrypsin deficiency using oligonucleotide probe analysis.</strong>
|
|
Hum. Genet. 79: 190-192, 1988.
|
|
|
|
|
|
[PubMed: 2899055]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00280565]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morin, T., Martin, J.-P., Feldmann, G., Rueff, B., Benhamou, J.-P., Ropartz, C.
|
|
<strong>Heterozygous alpha (1)-antitrypsin deficiency and cirrhosis in adults, a fortuitous association.</strong>
|
|
Lancet 305: 250-251, 1975. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 46389]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(75)91143-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morse, J. O.
|
|
<strong>Alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 299: 1045-1048 and 1099-1105, 1978.
|
|
|
|
|
|
[PubMed: 360063]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197811092991905]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Neumann, F., Meirom, R., Rattner, D., Trainin, Z., Klopfer, U., Nobel, T. A.
|
|
<strong>Animal model of human disease: alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Path. 84: 427-430, 1976.
|
|
|
|
|
|
[PubMed: 133618]
|
|
|
|
|
|
|
|
</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">
|
|
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">
|
|
Perrault, J. L., Malo, J.-L., Bake, B., Renzi, G., Grassino, A.
|
|
<strong>Alpha-1-antitrypsin deficiency: genetic, clinical and functional correlations in a three generation family.</strong>
|
|
Respiration 37: 291-300, 1979.
|
|
|
|
|
|
[PubMed: 314139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000194041]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pierce, J. A., Eisen, A. Z., Dhingra, H. K.
|
|
<strong>Relationship of antitrypsin deficiency to the pathogenesis of emphysema.</strong>
|
|
Trans. Assoc. Am. Phys. 82: 87-97, 1969.
|
|
|
|
|
|
[PubMed: 5310288]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rodriguez-Cintron, W., Guntupalli, K., Fraire, A. E.
|
|
<strong>Bronchiectasis and homozygous (PiZZ) alpha1-antitrypsin deficiency in a young man.</strong>
|
|
Thorax 50: 424-425, 1995.
|
|
|
|
|
|
[PubMed: 7785020]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/thx.50.4.424]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rodriguez-Soriano, J., Fidalgo, I., Camarero, C., Vallo, A., Oliveros, R.
|
|
<strong>Juvenile cirrhosis and membranous glomerulonephritis in a child with alpha-1-antitrypsin deficiency PiSZ.</strong>
|
|
Acta Paediat. Scand. 67: 793-796, 1978.
|
|
|
|
|
|
[PubMed: 309702]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1978.tb16263.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenthal, P., Liebman, W. M., Thaler, M. M.
|
|
<strong>Alpha-1-antitrypsin deficiency and severe infantile liver disease.</strong>
|
|
Am. J. Dis. Child. 133: 1195-1196, 1979.
|
|
|
|
|
|
[PubMed: 315706]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archpedi.1979.02130110103023]
|
|
|
|
|
|
</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">
|
|
Schmitt, M. G., Jr., Phillips, R. B., Matzen, R. N., Rodey, G.
|
|
<strong>Alpha-1-antitrypsin deficiency: a study of the relationship between the Pi system and genetic markers.</strong>
|
|
Am. J. Hum. Genet. 27: 315-321, 1975.
|
|
|
|
|
|
[PubMed: 830072]
|
|
|
|
|
|
|
|
</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">
|
|
Sharp, H. L., Bridges, R. A., Krivit, W., Freier, E. F.
|
|
<strong>Cirrhosis associated with alpha-1-antitrypsin deficiency: a previously unrecognized inherited disorder.</strong>
|
|
J. Lab. Clin. Med. 73: 934-939, 1969.
|
|
|
|
|
|
[PubMed: 4182334]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sigsgaard, T., Brandslund, I., Rasmussen, J. B., Lund, E. D., Varming, H.
|
|
<strong>Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.</strong>
|
|
Pharmacogenetics 4: 135-141, 1994.
|
|
|
|
|
|
[PubMed: 7920693]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00008571-199406000-00004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sigsgaard, T., Pedersen, O. F., Juul, S., Gravesen, S.
|
|
<strong>Respiratory disorders and atopy in cotton, wool and other textile mill workers in Denmark.</strong>
|
|
Am. J. Ind. Med. 22: 163-184, 1992.
|
|
|
|
|
|
[PubMed: 1415284]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajim.4700220204]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Song, S., Morgan, M., Ellis, T., Poirier, A., Chesnut, K., Wang, J., Brantly, M., Muzyczka, N., Byrne, B. J., Atkinson, M., Flotte, T. R.
|
|
<strong>Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 14384-14388, 1998.
|
|
|
|
|
|
[PubMed: 9826709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.95.24.14384]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Starzl, T. E., Porter, K. A., Francavilla, A., Iwatsuki, S.
|
|
<strong>Reversal of hepatic alpha-1-antitrypsin deposition after portacaval shunt.</strong>
|
|
Lancet 322: 424-426, 1983. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 6135912]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(83)90390-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stevens, P. M., Hnilica, V., Johnson, P. C., Bell, R. L.
|
|
<strong>Pathophysiology of hereditary emphysema.</strong>
|
|
Ann. Intern. Med. 74: 672-680, 1971.
|
|
|
|
|
|
[PubMed: 4104410]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-74-5-672]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stockley, R. A.
|
|
<strong>Alpha-1-antitrypsin phenotypes in cor pulmonale due to chronic obstructive airways disease.</strong>
|
|
Quart. J. Med. 48: 419-428, 1979.
|
|
|
|
|
|
[PubMed: 317359]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Talamo, R. C., Allen, J. D., Kahan, M. G., Austen, K. F.
|
|
<strong>Hereditary alpha-1-antitrypsin deficiency.</strong>
|
|
New Eng. J. Med. 278: 345-351, 1968.
|
|
|
|
|
|
[PubMed: 4169707]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM196802152780701]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Talamo, R. C., Feingold, M.
|
|
<strong>Infantile cirrhosis with hereditary alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Dis. Child. 125: 845-849, 1973.
|
|
|
|
|
|
[PubMed: 4196606]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archpedi.1973.04160060051011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tarkoff, M. P., Kueppers, F., Miller, W. F.
|
|
<strong>Pulmonary emphysema and alpha-1-antitrypsin deficiency.</strong>
|
|
Am. J. Med. 45: 220-228, 1968.
|
|
|
|
|
|
[PubMed: 5666650]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(68)90040-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Townley, R. G., Ryning, F., Lynch, H. T., Brody, A. W.
|
|
<strong>Obstructive lung disease in hereditary alpha-1-antitrypsin deficiency.</strong>
|
|
JAMA 214: 325-331, 1970.
|
|
|
|
|
|
[PubMed: 5469071]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Udall, J. N., Bloch, K. J., Walker, W. A.
|
|
<strong>Transport of proteases across neonatal intestine and development of liver disease in infants with alpha-1-antitrypsin deficiency.</strong>
|
|
Lancet 319: 1441-1443, 1982. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 6123724]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(82)92454-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weber, W., Weidinger, S.
|
|
<strong>PI S-Cologne: a new variant in the alpha-1-antitrypsin system.</strong>
|
|
Hum. Genet. 80: 102, 1988.
|
|
|
|
|
|
[PubMed: 3262085]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00451468]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weitz, J. I., Silverman, E. K., Thong, B., Campbell, E. J.
|
|
<strong>Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype: evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha-1-proteinase inhibitor.</strong>
|
|
J. Clin. Invest. 89: 766-773, 1992.
|
|
|
|
|
|
[PubMed: 1541671]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115654]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wewers, M. D., Casolaro, A., Sellers, S., Swayze, S. C., McPhaul, K. M., Wittes, J. T., Crystal, R. G.
|
|
<strong>Replacement therapy for alpha-1-antitrypsin deficiency associated with emphysema.</strong>
|
|
New Eng. J. Med. 316: 1055-1062, 1987.
|
|
|
|
|
|
[PubMed: 3494198]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198704233161704]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wiebicke, W., Niggemann, B., Fischer, A.
|
|
<strong>Pulmonary function in children with homozygous alpha-1-protease inhibitor deficiency.</strong>
|
|
Europ. J. Pediat. 155: 603-607, 1996.
|
|
|
|
|
|
[PubMed: 8831086]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01957913]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilcke, J. T. R., Seersholm, N., Kok-Jensen, A., Dirksen, A.
|
|
<strong>Transmitting genetic risk information in families: attitudes about disclosing the identity of relatives.</strong>
|
|
Am. J. Hum. Genet. 65: 902-909, 1999.
|
|
|
|
|
|
[PubMed: 10441594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302531]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, Y., Whitman, I., Molmenti, E., Moore, K., Hippenmeyer, P., Perlmutter, D. H.
|
|
<strong>A lag in intracellular degradation of mutant alpha-1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha-1-antitrypsin deficiency.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 9014-9018, 1994.
|
|
|
|
|
|
[PubMed: 8090762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.91.19.9014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yusa, K., Rashid, S. T., Strick-Marchand, H., Varela, I., Liu, P.-Q., Paschon, D. E., Miranda, E., Ordonez, A., Hannan, N. R. F., Rouhani, F. J., Darche, S., Alexander, G., Marciniak, S. J., Fusaki, N., Hasegawa, M., Holmes, M. C., Di Santo, J. P., Lomas, D. A., Bradley, A., Vallier, L.
|
|
<strong>Targeted gene correction of alpha-1-antitrypsin deficiency in induced pluripotent stem cells.</strong>
|
|
Nature 478: 391-394, 2011.
|
|
|
|
|
|
[PubMed: 21993621]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10424]
|
|
|
|
|
|
</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">
|
|
Anne M. Stumpf - updated : 4/18/2013<br>Ada Hamosh - updated : 11/29/2011<br>Ada Hamosh - updated : 8/17/2010
|
|
</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">
|
|
Carol A. Bocchini : 7/20/2010
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 10/24/2024<br>carol : 10/23/2024<br>carol : 03/22/2022<br>carol : 09/19/2019<br>carol : 09/18/2019<br>carol : 08/04/2016<br>carol : 07/09/2016<br>carol : 7/9/2016<br>carol : 2/10/2016<br>joanna : 2/9/2016<br>alopez : 4/18/2013<br>terry : 8/8/2012<br>alopez : 12/1/2011<br>terry : 11/29/2011<br>terry : 9/1/2010<br>alopez : 8/18/2010<br>terry : 8/17/2010<br>carol : 8/13/2010<br>carol : 8/13/2010
|
|
</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>
|
|
|
|
|