7125 lines
729 KiB
Text
7125 lines
729 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
|
|
|
|
- #306900 - HEMOPHILIA B; HEMB
|
|
|
|
|
|
- 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=306900"><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">#306900</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/306900"><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="#inheritance">Inheritance</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="#diagnosis">Diagnosis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneTherapy">Gene Therapy</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<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=HEMOPHILIA B" 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=17869&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Severe hemophilia B </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17870&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Moderate hemophilia B </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17871&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mild hemophilia B </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17997&Typ=Pat" title="Bleeding disorder in hemophilia B carriers" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Bleeding disorder in hemop… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=13896&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hemophilia B </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1495/" 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/3315" 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/hemophilia" 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=306900[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=169793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Severe hemophilia B</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Moderate hemophilia B</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mild hemophilia B</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=177929" title="Bleeding disorder in hemophilia B carriers" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Bleeding disorder in hemop…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hemophilia B</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:12259" 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/306900" 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/OMIA000438/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:306900" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 41788008, 767712006<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> D67<br />
|
|
|
|
|
|
<strong>ICD9CM:</strong> 286.1<br />
|
|
|
|
|
|
<strong>ORPHA:</strong> 169793, 169796, 169799, 177929, 98879<br />
|
|
|
|
|
|
<strong>DO:</strong> 12259<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>
|
|
306900
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HEMOPHILIA B; HEMB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CHRISTMAS DISEASE<br />
|
|
FACTOR IX DEFICIENCY<br />
|
|
F9 DEFICIENCY<br />
|
|
PLASMA THROMBOPLASTIN COMPONENT DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
HEMOPHILIA B(M), INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
HEMOPHILIA B LEYDEN, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/739?start=-3&limit=10&highlight=739">
|
|
Xq27.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hemophilia B
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/306900"> 306900 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
F9
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/300746"> 300746 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/306900" 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/306900" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/306900" 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">
|
|
|
|
- X-linked recessive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845977</a>, <a href="https://bioportal.bioontology.org/search?q=C1279481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1279481</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Factor IX deficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/767712006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">767712006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/41788008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">41788008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D67" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D67</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/286.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">286.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008533&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008533</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">
|
|
|
|
- Factor IX deficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/767712006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">767712006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/41788008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">41788008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D67" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D67</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/286.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">286.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008533&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008533</a>]</span><br /> -
|
|
PTT prolonged <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409675001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409675001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240671&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240671</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003645</a>]</span><br /> -
|
|
PT normal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844369&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844369</a>]</span><br /> -
|
|
Platelet count normal <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165555003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165555003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427564&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427564</a>]</span><br /> -
|
|
Platelet function normal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0855741&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0855741</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">
|
|
|
|
- Patient with factor IX Leyden variants (see, e.g., <a href="/entry/300746#0001">300746.0001</a>) have bleeding in childhood that improves or resolves after puberty<br /> -
|
|
Patients with hemophilia B(M) variants (see, e.g., <a href="/entry/300746#0030">300746.0030</a>) also have prolonged PT<br /> -
|
|
Phenotypically indistinguishable from hemophilia A (<a href="/entry/306700">306700</a>)<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 coagulation factor IX gene (F9, <a href="/entry/300746#0001">300746.0001</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 hemophilia B (HEMB), also known as Christmas disease, is caused by mutation in the gene encoding coagulation factor IX (F9; <a href="/entry/300746">300746</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>Hemophilia B (HEMB), which results from factor IX deficiency, is phenotypically indistinguishable from hemophilia A (<a href="/entry/306700">306700</a>), which results from coagulation factor VIII (F8; <a href="/entry/300841">300841</a>) deficiency. The classic laboratory findings in hemophilia B include a prolonged activated partial thromboplastin time (aPTT) and a normal prothrombin time (PT) (<a href="#78" class="mim-tip-reference" title="Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R. <strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong> Am. J. Hemat. 43: 177-182, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>] [<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8352232">Lefkowitz et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8352232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Early studies made a distinction between cross-reactive-material (CRM)-negative and CRM-positive hemophilia B mutants. This classification referred to detection of the F9 antigen in plasma, even in the presence of decreased F9 activity. Detection of the antigen indicated the presence of a dysfunctional F9 protein. <a href="#105" class="mim-tip-reference" title="Roberts, H. R., Grizzle, J. E., McLester, W. D., Penick, G. D. <strong>Genetic variants of hemophilia B: detection by means of a specific PTC inhibitor.</strong> J. Clin. Invest. 47: 360-365, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12066779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12066779</a>] [<a href="https://doi.org/10.1172/JCI105732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12066779">Roberts et al. (1968)</a> found that about 90% of patients with hemophilia B were CRM-negative, whereas about 10% were CRM-positive. However, <a href="#7" class="mim-tip-reference" title="Bertina, R. M., Veltkamp, J. J. <strong>The abnormal factor IX of hemophilia B+ variants.</strong> Thromb. Haemost. 40: 335-349, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/734633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">734633</a>]" pmid="734633">Bertina and Veltkamp (1978)</a> found that a rather large proportion of the hemophilia B patients could be characterized as hemophilia B CRM+. They identified 14 cases of hemophilia B CRM+ from 11 families among a group of 33 patients. After immunologic and activity comparisons, they found at least 7 different factor IX variants. <a href="#7" class="mim-tip-reference" title="Bertina, R. M., Veltkamp, J. J. <strong>The abnormal factor IX of hemophilia B+ variants.</strong> Thromb. Haemost. 40: 335-349, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/734633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">734633</a>]" pmid="734633">Bertina and Veltkamp (1978)</a> noted the high heterogeneity within this group. In an editorial on variants of vitamin K-dependent coagulation factors, <a href="#6" class="mim-tip-reference" title="Bertina, R. M., Briet, E., Veltkamp, J. J. <strong>Variants of vitamin K dependent coagulation factors. (Editorial)</strong> Acta Haemat. 62: 1-3, 1979."None>Bertina et al. (1979)</a> stated that 9 defective variants of factor II, 5 variants of factor X, and many variants (about 180 pedigrees) of factor IX had been identified. At least one variant of factor VII (Padua) was also known. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12066779+734633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#1" class="mim-tip-reference" title="Aggeler, P. M., White, S. G., Glendening, M. B., Page, E. W., Leake, T. B., Bates, G. <strong>Plasma thromboplastin component (PTC) deficiency: a new disease resembling hemophilia.</strong> Proc. Soc. Exp. Biol. Med. 79: 692-694, 1952.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14920537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14920537</a>] [<a href="https://doi.org/10.3181/00379727-79-19488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14920537">Aggeler et al. (1952)</a> described a 16-year-old white male with a hemophilia-like disorder in which there appeared to be a deficiency of a coagulation factor, which the authors called 'plasma thromboplastin component' (PTC). They cited reports indicating that blood from some patients with hemophilia was capable of correcting the coagulation defect in other cases of hemophilia in vitro. The authors concluded that these patients had a combined defect of PTC deficiency and 'true' hemophilia (hemophilia A). It was not clear at that time if the disorder was hereditary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14920537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#8" class="mim-tip-reference" title="Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R. <strong>Christmas disease: a condition previously mistaken for haemophilia.</strong> Brit. Med. J. 2: 1378-1382, 1952.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12997790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12997790</a>] [<a href="https://doi.org/10.1136/bmj.2.4799.1378" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12997790">Biggs et al. (1952)</a> in the December 27 (Christmas) issue of the British Medical Journal reported a 5-year-old boy, with a surname of 'Christmas' who had this disorder, as well as other patients, some of whom came from families showing a typical X-linked pattern of inheritance, <a href="#8" class="mim-tip-reference" title="Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R. <strong>Christmas disease: a condition previously mistaken for haemophilia.</strong> Brit. Med. J. 2: 1378-1382, 1952.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12997790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12997790</a>] [<a href="https://doi.org/10.1136/bmj.2.4799.1378" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12997790">Biggs et al. (1952)</a> defended the familial eponym in the following way: 'The naming of clinical disorders after patients was introduced by Sir Jonathan Hutchinson and is now familiar from serological research; it has the advantage that no hypothetical implication is attached to such a name.' <a href="#34" class="mim-tip-reference" title="Giangrande, P. L. F. <strong>Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors.</strong> Brit. J. Haemat. 121: 703-712, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12780784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12780784</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2003.04333.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12780784">Giangrande (2003)</a> provided historical information concerning the patient Stephen Christmas (1947-1993), whose mutation in the F9 gene (<a href="/entry/300746#0109">300746.0109</a>) was reported by <a href="#115" class="mim-tip-reference" title="Taylor, S. A. M., Duffin, J., Cameron, C., Teitel, J., Garvey, B., Lillicrap, D. P. <strong>Characterization of the original Christmas disease mutation (cysteine 206-to-serine): from clinical recognition to molecular pathogenesis.</strong> Thromb. Haemost. 67: 63-65, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1615485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1615485</a>]" pmid="1615485">Taylor et al. (1992)</a> and his physicians. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12997790+1615485+12780784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Hemophilia B(M)</em></strong></p><p>
|
|
A subset of hemophilia B patients have a prolonged prothrombin time when exposed to bovine (or ox) brain tissue, which serves as a source of thromboplastin, or tissue factor (F3; <a href="/entry/134390">134390</a>); these CRM+ patients are classified as having hemophilia B(M) (<a href="#78" class="mim-tip-reference" title="Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R. <strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong> Am. J. Hemat. 43: 177-182, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>] [<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8352232">Lefkowitz et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8352232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 workers (e.g., <a href="#94" class="mim-tip-reference" title="Nour-Eldin, F., Wilkinson, J. F. <strong>Factor-VII deficiency with Christmas disease in one family.</strong> Lancet 273: 1173-1176, 1959. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13666001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13666001</a>] [<a href="https://doi.org/10.1016/s0140-6736(59)91184-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13666001">Nour-Eldin and Wilkinson, 1959</a>) observed the combination of factor IX deficiency with factor VII (F7; <a href="/entry/613878">613878</a>) deficiency. However, inheritance was always X-linked, even though F7 is on chromosome 13. <a href="#118" class="mim-tip-reference" title="Verstraete, M., Vermylen, C., Vandenbroucke, J. <strong>Hemophilia B associated with a decreased factor VII activity.</strong> Am. J. Med. Sci. 243: 20-26, 1962.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13925578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13925578</a>] [<a href="https://doi.org/10.1097/00000441-196201000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13925578">Verstraete et al. (1962)</a> reported 4 families in which all affected males had both Christmas disease and factor VII deficiency. The authors suggested that factor VII deficiency was a consistent secondary phenomenon; thus no separate mutation for the combined defect would be necessary. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13925578+13666001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#61" class="mim-tip-reference" title="Hougie, C., Twomey, J. J. <strong>Hemophilia B(M): a new type of factor-IX deficiency.</strong> Lancet 289: 698-700, 1967. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4163943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4163943</a>] [<a href="https://doi.org/10.1016/s0140-6736(67)92179-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4163943">Hougie and Twomey (1967)</a> defined a variant of hemophilia B that differed from the usual form by the presence of a prolonged PT. They presented evidence these patients had a structurally abnormal and inactive form of factor IX that acted as an inhibitor of the normal reaction between factor VII and bovine brain. They called the variant hemophilia B(M), after the initial of the family surname. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4163943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Denson, K. W., Biggs, P., Mannucci, P. M. <strong>An investigation of three patients with Christmas disease due to an abnormal type of factor IX.</strong> J. Clin. Path. 21: 160-165, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4972271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4972271</a>] [<a href="https://doi.org/10.1136/jcp.21.2.160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4972271">Denson et al. (1968)</a> identified 3 blood samples of hemophilia B(M) among samples derived from 27 patients with Christmas disease. In a series of coagulation assays, <a href="#27" class="mim-tip-reference" title="Denson, K. W., Biggs, P., Mannucci, P. M. <strong>An investigation of three patients with Christmas disease due to an abnormal type of factor IX.</strong> J. Clin. Path. 21: 160-165, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4972271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4972271</a>] [<a href="https://doi.org/10.1136/jcp.21.2.160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4972271">Denson et al. (1968)</a> demonstrated that the prolongation of the PT involved inhibition of the reaction between ox brain tissue factor, factor VII, and factor X. Noting that this distinct abnormality had only been observed in patients with factor IX deficiency, the authors postulated that the 'inhibitor' may be an abnormal protein similar to or identical with factor IX. Subsequent studies showed that this inhibitor was an abnormal form of factor IX that was functionally inactive but was antigenically indistinguishable from normal factor IX. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4972271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#78" class="mim-tip-reference" title="Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R. <strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong> Am. J. Hemat. 43: 177-182, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>] [<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8352232">Lefkowitz et al. (1993)</a> noted that the bovine brain tissue in studies of hemophilia B(M) is the source of thromboplastin, or tissue factor (F3; <a href="/entry/134390">134390</a>); PT times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. However, in various studies of factor IX Hilo (<a href="/entry/300746#0031">300746.0031</a>), <a href="#78" class="mim-tip-reference" title="Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R. <strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong> Am. J. Hemat. 43: 177-182, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>] [<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8352232">Lefkowitz et al. (1993)</a> found that either normal F9 or Hilo F9 prolonged the PT regardless of the tissue factor source, but the prolongation required high concentrations of factor IX when rabbit or human brain was used. With bovine thromboplastin, factor IX Hilo was significantly better than normal factor IX at prolonging the PT. In addition, the prolongation times depended on the amounts of factors IX and X used in the assays. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8352232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Hemophilia B Leyden</em></strong></p><p>
|
|
<a href="#117" class="mim-tip-reference" title="Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A. <strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong> Scand. J. Haemat. 7: 82-90, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450691</a>] [<a href="https://doi.org/10.1111/j.1600-0609.1970.tb01873.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5450691">Veltkamp et al. (1970)</a> described a variant of hemophilia B, termed hemophilia B Leyden, in a Dutch family. The disorder was characterized by the disappearance of the bleeding diathesis as the patient aged. In affected individuals, plasma factor IX levels were less than 1% of normal before puberty, but after puberty factor IX activity and antigen levels rose steadily in a 1:1 ratio to a maximum of 50 to 60%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5450691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Briet, E., Bertina, R. M., van Tilburg, N. H., Veltkamp, J. J. <strong>Hemophilia B Leyden: a sex-linked hereditary disorder that improves after puberty.</strong> New Eng. J. Med. 306: 788-790, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7062952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7062952</a>] [<a href="https://doi.org/10.1056/NEJM198204013061306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7062952">Briet et al. (1982)</a> described a similar variant of hemophilia B that took a severe form early in life but remitted after puberty, with an increase in factor IX levels from below 1% of normal to about 50% of normal by age 80 years. Three pedigrees with 27 affected males with this disorder could be traced to a small village in the east of the Netherlands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7062952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 Dutch pedigrees with hemophilia B Leyden, <a href="#104" class="mim-tip-reference" title="Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E. <strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong> Blood 72: 1074, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416069</a>]" pmid="3416069">Reitsma et al. (1988)</a> found that patients with hemophilia B Leyden had a mutation in the promoter region of the F9 gene (<a href="/entry/300746#0001">300746.0001</a>). The findings suggested that a point mutation could lead to a switch from constitutive to steroid hormone-dependent gene expression. The families were probably related. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3416069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#83" class="mim-tip-reference" title="Mandalaki, T., Louizou, C., Dimitriadou, C., Briet, E. <strong>Haemophilia B Leyden in Greece.</strong> Thromb. Haemost. 56: 340-342, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3563965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3563965</a>]" pmid="3563965">Mandalaki et al. (1986)</a> reported a 5-generation Greek family with hemophilia B. The factor IX levels in the 3 patients from the last generation were extremely low, while those of patients in the older generations were much higher. In 1 patient, the rise of factor IX levels appeared between ages 13 and 14 years. In addition, older patients in the family had much milder symptoms compared to the younger patients. The phenotype was similar to hemophilia B Leyden as described by <a href="#117" class="mim-tip-reference" title="Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A. <strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong> Scand. J. Haemat. 7: 82-90, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450691</a>] [<a href="https://doi.org/10.1111/j.1600-0609.1970.tb01873.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5450691">Veltkamp et al. (1970)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3563965+5450691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Manifesting Females</em></strong></p><p>
|
|
<a href="#77" class="mim-tip-reference" title="Lascari, A. D., Hoak, J. C., Taylor, J. C. <strong>Christmas disease in a girl.</strong> Am. J. Dis. Child. 117: 585-588, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5781711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5781711</a>] [<a href="https://doi.org/10.1001/archpedi.1969.02100030587016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5781711">Lascari et al. (1969)</a> described a daughter of a male with hemophilia B who had an XX karyotype, factor IX level of 5%, and hemarthrosis. The factor IX level in the mother was 100%. The girl was thought to be a manifesting heterozygote with unfortunate lyonization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5781711" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#111" class="mim-tip-reference" title="Spinelli, A., Schmid, W., Straub, P. W. <strong>Christmas disease (haemophilia B) in a girl with deletion of the short arm of one X-chromosome (functional Turner syndrome).</strong> Brit. J. Haemat. 34: 129-135, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/952762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">952762</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1976.tb00181.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="952762">Spinelli et al. (1976)</a> observed deletion of the short arm of 1 of the X chromosomes in a female with hemophilia B. Family investigations were negative. <a href="#54" class="mim-tip-reference" title="Hashmi, K. Z., MacIver, J. E., Delamore, I. W. <strong>Christmas disease in a female.</strong> Lancet 312: 965-966, 1978. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/81989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">81989</a>] [<a href="https://doi.org/10.1016/s0140-6736(78)92528-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="81989">Hashmi et al. (1978)</a> reported a girl with Christmas disease. Her father was affected, and her parents were related as first cousins, suggesting possible homozygosity for the defect. They referred to a similar instance of plausible homozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=952762+81989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#122" class="mim-tip-reference" title="Wadelius, C., Lindstedt, M., Pigg, M., Egberg, N., Pettersson, U., Anvret, M. <strong>Hemophilia B in a 46,XX female probably caused by non-random X inactivation.</strong> Clin. Genet. 43: 1-4, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8096443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8096443</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1993.tb04415.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8096443">Wadelius et al. (1993)</a> reported a female with hemophilia B with factor IX activity of about 1%. Her father had severe hemophilia B. No chromosomal abnormality could be detected, and DNA analysis gave no indication of deletions or mutations of TaqI cleavage sites in the F9 gene. Analysis of the methylation pattern of locus DXS255 indicated that the expression of hemophilia B in this girl was caused by nonrandom X inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8096443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#119" class="mim-tip-reference" title="Vianna-Morgante, A. M., Batista, D. A. S., Levisky, R. B., Zatz, M. <strong>X;autosome translocations in females with X-linked recessive diseases. (Abstract)</strong> 7th International Congress of Human Genetics, Berlin 1986. P. 97."None>Vianna-Morgante et al. (1986)</a> observed de novo t(X;1)(q27;q23) in a girl with hemophilia B who had no affected relatives. In a full description of the case, <a href="#74" class="mim-tip-reference" title="Krepischi-Santos, A. C. V., Carneiro, J. D. A., Svartman, M., Bendit, I., Odone-Filho, V., Vianna-Morgante, A. M. <strong>Deletion of the factor IX gene as a result of translocation t(X;1) in a girl affected by haemophilia B.</strong> Brit. J. Haemat. 113: 616-620, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11380446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11380446</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02786.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11380446">Krepischi-Santos et al. (2001)</a> stated that the translocated X was preferentially active and that methylation analysis of the DXS255 locus confirmed the skewed X inactivation with the paternal allele being the active one. Molecular analysis showed deletion of at least part of the F9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11380446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Nisen, P., Stamberg, J., Ehrenpreis, R., Velasco, S., Shende, A., Engelberg, J., Karayalcin, G., Waber, L. <strong>The molecular basis of severe hemophilia B in a girl.</strong> New Eng. J. Med. 315: 1139-1142, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3093864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3093864</a>] [<a href="https://doi.org/10.1056/NEJM198610303151806" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3093864">Nisen et al. (1986)</a> described hemophilia B in a girl with the karyotype 46,X,del(X)q27. They showed that the X chromosome with the deletion was inactivated in all cells. The mother's identical twin sister had a son with severe hemophilia B. The proband was also lacking the paternal factor VIII gene, indicating that the deletion had occurred in the paternal X chromosome and had included the factor VIII locus. However, both the maternal and the paternal factor IX loci were present. The interpretation applied by <a href="#93" class="mim-tip-reference" title="Nisen, P., Stamberg, J., Ehrenpreis, R., Velasco, S., Shende, A., Engelberg, J., Karayalcin, G., Waber, L. <strong>The molecular basis of severe hemophilia B in a girl.</strong> New Eng. J. Med. 315: 1139-1142, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3093864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3093864</a>] [<a href="https://doi.org/10.1056/NEJM198610303151806" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3093864">Nisen et al. (1986)</a> was that inactivation of the deleted, paternally derived X chromosome in all cells had provided the opportunity for expression of the hemophilia B gene which the proband had inherited from her mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3093864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 sequencing the complete factor IX gene in 2 sisters with hemophilia B with different phenotypes and no family history of hemorrhagic diathesis, <a href="#22" class="mim-tip-reference" title="Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M. <strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong> Blood 96: 1585-1587, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942410</a>]" pmid="10942410">Costa et al. (2000)</a> found a common 5-prime splice site mutation in intron 3 (<a href="/entry/300746#0107">300746.0107</a>) and an additional missense mutation (I344T; <a href="/entry/300746#0108">300746.0108</a>) in 1 sister. The presence of dysfunctional antigen in the latter strongly suggested that these mutations were in trans. Neither mutation was found in leukocyte DNA from the asymptomatic parents, but the mother was a somatic mosaic for the shared splice site mutation. The somatic mosaicism in the mother for the splice site mutation was demonstrated by studies of buccal and uroepithelial cells. The missense mutation was presumed to have resulted from a de novo mutation in the father's gametes. The compound heterozygous proband was a 14-year-old girl with moderate hemophilia B, manifest by hematomas, hemarthrosis, and epistaxis. A sister suffered only from rare hematomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a population-based survey in the Netherlands, <a href="#100" class="mim-tip-reference" title="Plug, I., Mauser-Bunschoten, E. P., Brocker-Vriends, A. H. J. T., van Amstel, H. K. P., van der Bom, J. G., van Diemen-Homan, J. E. M., Willemse, J., Rosendaal, F. R. <strong>Bleeding in carriers of hemophilia.</strong> Blood 108: 52-56, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16551972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16551972</a>] [<a href="https://doi.org/10.1182/blood-2005-09-3879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16551972">Plug et al. (2006)</a> found that female carriers of hemophilia A and B bled more frequently than noncarrier women, especially after medical procedures, such as tooth extraction or tonsillectomy. Reduced clotting factor levels correlated with a mild hemophilia phenotype. Variation in clotting levels was attributed to lyonization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16551972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Chronic synovitis occurs in about 10% of Indian patients with severe hemophilia. <a href="#33" class="mim-tip-reference" title="Ghosh, K., Shankarkumar, U., Shetty, S., Mohanty, D. <strong>Chronic synovitis and HLA B27 in patients with severe haemophilia.</strong> Lancet 361: 933-934, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12648975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12648975</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)12763-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12648975">Ghosh et al. (2003)</a> reported an association between the development of chronic synovitis in patients with hemophilia and the HLA-B27 allele (<a href="/entry/142830#0001">142830.0001</a>). They studied 473 patients, 424 with hemophilia A and 49 with hemophilia B. Twenty-one (64%) of 33 patients with both disorders had HLA-B27, compared to 23 (5%) of 440 with severe hemophilia without synovitis (odds ratio of 31.6). There were 3 sib pairs with hemophilia in whom only 1 sib had synovitis; all the affected sibs had the HLA-B27 allele, whereas the unaffected sibs did not. Chronic synovitis presented as swelling of the joint with heat and redness and absence of response to treatment with factor concentrate. <a href="#33" class="mim-tip-reference" title="Ghosh, K., Shankarkumar, U., Shetty, S., Mohanty, D. <strong>Chronic synovitis and HLA B27 in patients with severe haemophilia.</strong> Lancet 361: 933-934, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12648975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12648975</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)12763-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12648975">Ghosh et al. (2003)</a> suggested that patients with HLA-B27 may not be able to easily downregulate inflammatory mediators after bleeding in the joints, leading to chronic synovitis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12648975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Hemophilia B is classically transmitted as an X-linked recessive disorder. <a href="#26" class="mim-tip-reference" title="Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F. <strong>Germline mosaicism resulting in the transmission of severe hemophilia B from a grandfather with a mild deficiency.</strong> Am. J. Med. Genet. 129A: 13-15, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266608</a>] [<a href="https://doi.org/10.1002/ajmg.a.30162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266608">Cutler et al. (2004)</a> described a family in which the usual pattern of X-linked inheritance of hemophilia B was complicated by mosaicism in the proband's maternal grandfather. The proband was a male infant with severe factor IX deficiency who was initially thought to be a sporadic case. Testing of other family members identified his mother as a carrier and his asymptomatic maternal grandfather as having very mild factor IX deficiency. The causative mutation was identified as a 2-bp deletion (AG within codons 134-135) in the F9 gene (<a href="/entry/300746#0110">300746.0110</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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><strong><em>Acquired Inhibitor</em></strong></p><p>
|
|
The treatment for factor IX deficiency is replacement of the missing coagulation factor by transfusion of plasma from a healthy individual. However, a subset of patients develop IgG antibodies against normal factor IX, which complicates treatment. <a href="#30" class="mim-tip-reference" title="George, J. N., Miller, G. M., Breckenridge, R. T. <strong>Studies on Christmas disease: investigation and treatment of a familial acquired inhibitor of factor IX.</strong> Brit. J. Haemat. 21: 333-342, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4998792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4998792</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1971.tb03445.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4998792">George et al. (1971)</a> reported a family in which 3 of 4 members with Christmas disease developed an inhibitor to factor IX after transfusion. The inhibitor was an IgG antibody directed against the activated form of factor IX (IXa). There was no immunologically detectable factor IX-like material in the affected family members without an inhibitor. The findings were consistent with previous postulates that inhibitors to factor IX develop only in patients with Christmas disease who lack the factor IX antigen. The fourth member of the family, who had no factor IX antigen, was transfused several times, but failed to develop antibodies to factor IX. <a href="#30" class="mim-tip-reference" title="George, J. N., Miller, G. M., Breckenridge, R. T. <strong>Studies on Christmas disease: investigation and treatment of a familial acquired inhibitor of factor IX.</strong> Brit. J. Haemat. 21: 333-342, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4998792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4998792</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1971.tb03445.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4998792">George et al. (1971)</a> noted that inhibitors to factor IX develop infrequently compared to factor VIII, suggesting that there may be a predisposition to the development of an inhibitor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4998792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G. <strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong> Nature 303: 181-182, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6843667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6843667</a>] [<a href="https://doi.org/10.1038/303181a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6843667">Giannelli et al. (1983)</a> noted that treatment of patients with factor IX deficiency with normal plasma resulted in the development of specific anti-F9 antibodies in about 1% of all cases and about 2.5% of severe cases. The authors postulated that this may be due to complete absence of 'self' factor IX in the plasma recipient, such that the immune system regards the infused normal factor IX as foreign. Indeed, 4 patients with factor IX deficiency and F9 antibodies were found to have gross deletions in the F9 gene, resulting in complete absence of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6843667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with severe F9 deficiency who had developed a high-titer antibody, <a href="#55" class="mim-tip-reference" title="Hassan, H. J., Leonardi, A., Guerriero, R., Chelucci, C., Cianetti, L., Ciavarella, N., Ranieri, P., Pilolli, D., Peschle, C. <strong>Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.</strong> Blood 66: 728-730, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2992643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2992643</a>]" pmid="2992643">Hassan et al. (1985)</a> observed a deletion of about 33 kb at the F9 locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2992643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Southern blot analysis of 9 patients, including 2 brothers, with hemophilia B and F9 antibodies, <a href="#85" class="mim-tip-reference" title="Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L. <strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong> J. Clin. Invest. 79: 746-753, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029178</a>] [<a href="https://doi.org/10.1172/JCI112880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3029178">Matthews et al. (1987)</a> found that 2 had a total deletion of the F9 gene. The brothers were shown to have a presumably identical complex rearrangement of the gene involving 2 separate deletions. Five other patients had a structurally intact F9 gene. <a href="#85" class="mim-tip-reference" title="Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L. <strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong> J. Clin. Invest. 79: 746-753, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029178</a>] [<a href="https://doi.org/10.1172/JCI112880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3029178">Matthews et al. (1987)</a> concluded that whereas large structural defects in the F9 gene can predispose the patients to the development of antibody, the phenomenon can also be associated with other defects of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Green, P. M., Bentley, D. R., Mibashan, R. S., Giannelli, F. <strong>Partial deletion by illegitimate recombination of the factor IX gene in a haemophilia B family with two inhibitor patients.</strong> Molec. Biol. Med. 5: 95-106, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3398774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3398774</a>]" pmid="3398774">Green et al. (1988)</a> identified a partial deletion in the F9 gene in a boy and his uncle, both of whom had hemophilia B and inhibitors to factor IX. The mother of the boy was a carrier. The deletion, called 'London-1,' most likely arose by nonhomologous recombination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3398774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#121" class="mim-tip-reference" title="Wadelius, C., Blomback, M., Pettersson, U. <strong>Molecular studies of haemophilia B in Sweden: identification of patients with total deletion of the factor IX gene and without inhibitory antibodies.</strong> Hum. Genet. 81: 13-17, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848757</a>] [<a href="https://doi.org/10.1007/BF00283721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2848757">Wadelius et al. (1988)</a> found total deletion of the F9 gene in 3 affected males in 1 family who did not have antibodies against native factor IX. Two of the patients, who were cousins, had inherited the same maternal HLA haplotype, suggesting that immune gene(s) located at the MHC locus may be important for the development of antibodies against factor IX. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2848757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ljung, R., Petrini, P., Tengborn, L., Sjorin, E. <strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong> Brit. J. Haemat. 113: 81-86, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328285">Ljung et al. (2001)</a> found that 11 (23%) of 48 patients with severe hemophilia B developed inhibitors and all of them had deletions or nonsense mutations. Thus, 11 of 37 (30%) patients with severe hemophilia B as a result of deletion/nonsense mutations developed inhibitors compared with none of 11 patients with missense mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>In a patient with severe F9 deficiency who developed an inhibitor, <a href="#97" class="mim-tip-reference" title="Peake, I. R., Furlong, B. L., Bloom, A. L. <strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong> Lancet 323: 242-243, 1984. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142993</a>] [<a href="https://doi.org/10.1016/s0140-6736(84)90123-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6142993">Peake et al. (1984)</a> detected a deletion in the F9 gene using 4 genomic gene probes. Similar studies of 8 female relatives using this method identified 2 as carriers. Used a genomic probe containing a TaqI polymorphism in the F9 gene, <a href="#36" class="mim-tip-reference" title="Giannelli, F., Anson, D. S., Choo, K. H., Rees, D. J. G., Winship, P. R., Ferrari, N., Rizza, C. R., Brownlee, G. G. <strong>Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency).</strong> Lancet 323: 239-241, 1984. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142992</a>] [<a href="https://doi.org/10.1016/s0140-6736(84)90122-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6142992">Giannelli et al. (1984)</a> successfully identified carriers of Christmas disease in 3 affected families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6142993+6142992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In eukaryotic DNA, a high proportion of CpG dinucleotides are methylated at the cytosine residue to give 5-methylcytosine. The restriction enzyme HhaI will not cleave at methylated CpG sites, but PCR can overcome this limitation. <a href="#126" class="mim-tip-reference" title="Winship, P. R., Rees, D. J. G., Alkan, M. <strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong> Lancet 333: 631-634, 1989. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2564457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2564457</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)92141-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2564457">Winship et al. (1989)</a> used PCR to detect a polymorphic HhaI site located 8 kb 3-prime to the F9 gene and estimated that almost half of female subjects can be expected to be heterozygous at this site. Detection of this marker using PCR was predicted to increase the proportion of persons in whom the carrier state of hemophilia B could be diagnosed, compared to using the restriction enzyme alone, which could be influenced by methylation status. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2564457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Koeberl, D. D., Bottema, C. D. K., Sommer, S. S. <strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong> Am. J. Med. Genet. 35: 600-608, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970704</a>] [<a href="https://doi.org/10.1002/ajmg.1320350435" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1970704">Koeberl et al. (1990)</a> compared RFLP-based carrier detection of an X-linked disease with a direct method involving genomic amplification with transcript sequencing (GAWTS). They pointed out that the RFLP approach 'suffers from multiple levels of uncertainty.' They found that 22 at-risk females were diagnosed by direct testing, whereas only 11 females could be diagnosed by standard RFLP analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1970704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Giannelli, F., Green, P. M., High, K. A., Sommer, S., Lillicrap, D. P., Ludwig, M., Olek, K., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G. <strong>Haemophilia B: database of point mutations and short additions and deletions--third edition, 1992.</strong> Nucleic Acids Res. 20: 2027-2063, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1598234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1598234</a>] [<a href="https://doi.org/10.1093/nar/20.suppl.2027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1598234">Giannelli et al. (1992)</a> used hemophilia B as a model of a genetic disease with marked mutational heterogeneity to lay out an overall strategy for genetic counseling. They started with the construction of a national database which could be used for diagnosis and genetic counseling on the basis of DNA abnormality. In the U.K. there were just over 1,000 patients with hemophilia B and these were probably derived from 500 to 600 families. They characterized the mutation in a group of unrelated patients and in only 1 of 170 patients examined from the Swedish and British series did they fail to find a mutation in the essential regions of the gene. Thus the screening procedures used were capable of detecting all types of mutations. By phenotype/genotype correlations the authors generated information of prognostic value concerning each of those mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1598234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Prenatal Diagnosis</em></strong></p><p>
|
|
In 5 kindreds studied in detail, <a href="#101" class="mim-tip-reference" title="Poon, M.-C., Chui, D. H. K., Patterson, M., Starozik, D. M., Dimnik, L. S., Hoar, D. I. <strong>Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes.</strong> J. Clin. Invest. 79: 1204-1209, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2881949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2881949</a>] [<a href="https://doi.org/10.1172/JCI112938" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2881949">Poon et al. (1987)</a> were able to determine the carrier status of hemophilia B in all 11 females at risk; prenatal diagnosis could be offered to the offspring of each of the 6 carriers identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2881949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#49" class="mim-tip-reference" title="Green, P. M., Montandon, A. J., Bentley, D. R., Giannelli, F. <strong>Genetics and molecular biology of haemophilias A and B.</strong> Blood Coagul. Fibrinolysis 2: 539-565, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1768766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1768766</a>] [<a href="https://doi.org/10.1097/00001721-199108000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1768766">Green et al. (1991)</a> suggested a strategy for facilitating carrier and prenatal diagnosis by identification of all hemophilia B mutations in a given population so that only the relevant parts of the molecule need be focused on when performing amplification mismatch detection (AMD) as developed by <a href="#89" class="mim-tip-reference" title="Montandon, A. J., Green, P. M., Giannelli, F., Bentley, D. R. <strong>Direct detection of point mutations by mismatch analysis: application to haemophilia B.</strong> Nucleic Acids Res. 17: 3347-3358, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2726481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2726481</a>] [<a href="https://doi.org/10.1093/nar/17.9.3347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2726481">Montandon et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1768766+2726481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Linkage studies in the early 1960s suggested that the hemophilia A and B loci were not allelic; hemophilia A was found to be tightly linked to colorblindness (CBD; <a href="/entry/303800">303800</a>) on Xq28, whereas hemophilia B apparently was not linked to colorblindness. In the dog, <a href="#12" class="mim-tip-reference" title="Brinkhous, K. M., Davis, P. D., Graham, J. B., Dodds, W. J. <strong>Expression and linkage of genes for X-linked hemophilias A and B in the dog.</strong> Blood 41: 577-585, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4688873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4688873</a>]" pmid="4688873">Brinkhous et al. (1973)</a> showed that the loci for hemophilias A and B were probably 50 map units or more apart. The genetic distance between the 2 loci was estimated to be about 50 map units in man as well. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4688873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in situ hybridization, <a href="#103" class="mim-tip-reference" title="Purrello, M., Alhadeff, B., Esposito, D., Szabo, P., Rocchi, M., Truett, M., Masiarz, F., Siniscalco, M. <strong>The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.</strong> EMBO J. 4: 725-729, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3924593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3924593</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1985.tb03689.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3924593">Purrello et al. (1985)</a> showed that the loci for hemophilia A and hemophilia B flank the fragile X site (<a href="/entry/300624">300624</a>). The authors believed that this finding, combined with the knowledge that hemophilia B recombines freely with at least 2 loci of the G6PD (<a href="/entry/305900">305900</a>) cluster, supported the Siniscalco hypothesis that the chromosomal segment in which the fragile X site occurs is normally a region of high meiotic recombination (<a href="#112" class="mim-tip-reference" title="Szabo, P., Purrello, M., Rocchi, M., Archidiacono, N., Alhadeff, B., Filippi, G., Toniolo, D., Martini, G., Luzzatto, L., Siniscalco, M. <strong>Cytological mapping of the human glucose-6-phosphate dehydrogenase gene distal to the fragile-X site suggests a high rate of meiotic recombination across this site.</strong> Proc. Nat. Acad. Sci. 81: 7855-7859, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6595664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6595664</a>] [<a href="https://doi.org/10.1073/pnas.81.24.7855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6595664">Szabo et al., 1984</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6595664+3924593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Using genomic DNA probes, <a href="#18" class="mim-tip-reference" title="Chen, S.-H., Yoshitake, S., Chance, P. F., Bray, G. L., Thompson, A. R., Scott, C. R., Kurachi, K. <strong>An intragenic deletion of the factor IX gene in a family with hemophilia B.</strong> J. Clin. Invest. 76: 2161-2164, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3001143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3001143</a>] [<a href="https://doi.org/10.1172/JCI112222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3001143">Chen et al. (1985)</a> identified a partial intragenic deletion in the F9 gene in 7 affected members of a family with severe hemophilia B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a family with severe factor IX deficiency and no detectable factor IX protein, <a href="#116" class="mim-tip-reference" title="Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N. <strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong> Hum. Genet. 79: 273-276, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841226</a>] [<a href="https://doi.org/10.1007/BF00366250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2841226">Taylor et al. (1988)</a> identified a complete deletion of the F9 gene that extended at least 80 kb 3-prime of the gene. The proband did not have antibodies to factor IX, despite total deletion of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2841226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#86" class="mim-tip-reference" title="Matthews, R. J., Peake, I. R., Bloom, A. L., Anson, D. S. <strong>Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene.</strong> J. Med. Genet. 25: 779-780, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907054</a>] [<a href="https://doi.org/10.1136/jmg.25.11.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2907054">Matthews et al. (1988)</a> discussed the family originally reported by <a href="#97" class="mim-tip-reference" title="Peake, I. R., Furlong, B. L., Bloom, A. L. <strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong> Lancet 323: 242-243, 1984. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142993</a>] [<a href="https://doi.org/10.1016/s0140-6736(84)90123-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6142993">Peake et al. (1984)</a> as having an X-chromosome deletion of minimum size 114 kb that included the entire F9 gene. By isolation of further 3-prime flanking probes, they located the 3-prime breakpoint of the deletion to a position 145 kb 3-prime to the start of the F9 gene. Abnormal junction fragments detected at the breakpoint were used in the detection of carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2907054+6142993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with severe hemophilia B, <a href="#108" class="mim-tip-reference" title="Siguret, V., Amselem, S., Vidaud, M., Assouline, Z., Kerbiriou-Nabias, D., Pietu, G., Goossens, M., Larrieu, M. J., Bahnak, B., Meyer, D., Lavergne, J. M. <strong>Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.</strong> Brit. J. Haemat. 70: 411-416, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3219291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3219291</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1988.tb02509.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3219291">Siguret et al. (1988)</a> found loss of the Taq1 restriction site at the 5-prime end of exon 8 of the F9 gene. Using oligonucleotide probes and PCR-amplified DNA for sequencing of the affected region, the authors identified a C-to-T change in the catalytic domain of the protein, resulting in premature termination. The change resulted from a CpG mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3219291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 use of PCR followed by sequencing, <a href="#10" class="mim-tip-reference" title="Bottema, C. D. K., Koeberl, D. D., Sommer, S. S. <strong>Direct carrier testing in 14 families with haemophilia B.</strong> Lancet 334: 526-529, 1989. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2570235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2570235</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)90653-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2570235">Bottema et al. (1989)</a> identified mutations in the F9 gene (see, e.g., <a href="/entry/300746#0051">300746.0051</a>) in all 14 hemophilia B patients studied. Analysis for heterozygosity in at-risk female relatives was then done, either by sequencing the appropriate region or by detection of an altered restriction site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2570235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#49" class="mim-tip-reference" title="Green, P. M., Montandon, A. J., Bentley, D. R., Giannelli, F. <strong>Genetics and molecular biology of haemophilias A and B.</strong> Blood Coagul. Fibrinolysis 2: 539-565, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1768766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1768766</a>] [<a href="https://doi.org/10.1097/00001721-199108000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1768766">Green et al. (1991)</a> provided a list of point mutations that cause hemophilia B. <a href="#109" class="mim-tip-reference" title="Sommer, S. S., Bowie, E. J. W., Ketterling, R. P., Bottema, C. D. K. <strong>Missense mutations and the magnitude of functional deficit: the example of factor IX.</strong> Hum. Genet. 89: 295-297, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601420</a>] [<a href="https://doi.org/10.1007/BF00220543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1601420">Sommer et al. (1992)</a> estimated that missense mutations cause only 59% of moderate and severe hemophilia B and that these mutations are almost always (95%) of independent origin (i.e., de novo mutations). In contrast, missense mutations were found in virtually all (97%) families with mild disease and only a minority of these (41%) were of independent origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1768766+1601420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#39" class="mim-tip-reference" title="Giannelli, F., Green, P. M., High, K. A., Sommer, S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G. <strong>Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993.</strong> Nucleic Acids Res. 21: 3075-3087, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8392713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8392713</a>] [<a href="https://doi.org/10.1093/nar/21.13.3075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8392713">Giannelli et al. (1993)</a> reported on the findings in a database of 806 patients with hemophilia B in whom the defect in factor IX had been identified at the molecular level. A total of 379 independent mutations were described. The list included 234 different amino acid substitutions. There were 13 promoter mutations, 18 mutations in donor splice sites, 15 mutations in acceptor splice sites, and 4 mutations creating cryptic splice sites. In analyses of DNA from 290 families with hemophilia B (203 independent mutations), <a href="#67" class="mim-tip-reference" title="Ketterling, R. P., Vielhaber, E. L., Lind, T. J., Thorland, E. C., Sommer, S. S. <strong>The rates and patterns of deletions in the human factor IX gene.</strong> Am. J. Hum. Genet. 54: 201-213, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8304338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8304338</a>]" pmid="8304338">Ketterling et al. (1994)</a> found 12 deletions more than 20 bp long. Eleven of these were more than 2 kb long and one was 1.1 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8304338+8392713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G. <strong>Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.</strong> Nucleic Acids Res. 24: 103-118, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8594556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8594556</a>] [<a href="https://doi.org/10.1093/nar/24.1.103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8594556">Giannelli et al. (1996)</a> described the sixth edition of their hemophilia B database of point mutations and short (less than 30 bp) additions and deletions. The 1,380 patient entries were ordered by the nucleotide number of their mutation. References to published mutations were given and the laboratories generating the data were indicated. <a href="#41" class="mim-tip-reference" title="Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Figueiredo, M. S., Brownlee, G. G. <strong>Haemophilia B: database of point mutations and short additions and deletions, 7th edition.</strong> Nucleic Acids Res. 25: 133-135, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9016521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9016521</a>] [<a href="https://doi.org/10.1093/nar/25.1.133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9016521">Giannelli et al. (1997)</a> described the seventh edition of their database; 1,535 patient entries were ordered by the nucleotide number of their mutation. When known, details were given on factor IX activity, factor IX antigen in the circulation, presence of inhibitor, and origin of mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9016521+8594556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ljung, R., Petrini, P., Tengborn, L., Sjorin, E. <strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong> Brit. J. Haemat. 113: 81-86, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328285">Ljung et al. (2001)</a> surveyed a series comprising all 77 known families with hemophilia B in Sweden. The disorder was severe in 38, moderate in 10, and mild in 29. A total of 51 different mutations were found. Ten of the mutations, all C-to-T or G-to-A transitions, recurred in 1 to 6 additional families. Using haplotype analysis of 7 polymorphisms in the F9 gene, <a href="#82" class="mim-tip-reference" title="Ljung, R., Petrini, P., Tengborn, L., Sjorin, E. <strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong> Brit. J. Haemat. 113: 81-86, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328285">Ljung et al. (2001)</a> found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate hemophilia, 23 (48%) had a sporadic case compared with 31 families of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations; 11 of 23 of the mothers were proven carriers; and in the remaining 7 families, it was not possible to determine carriership. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#106" class="mim-tip-reference" title="Rogaev, E. I., Grigorenko, A. P., Faskhutdinova, G., Kittler, E. L. W., Moliaka, Y. K. <strong>Genotype analysis identifies the cause of the 'Royal disease.'</strong> Science 326: 817 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19815722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19815722</a>] [<a href="https://doi.org/10.1126/science.1180660" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19815722">Rogaev et al. (2009)</a> identified a splice site mutation in the F9 gene (<a href="/entry/300746#0113">300746.0113</a>) as the causative mutation for the 'Royal disease,' the form of hemophilia transmitted from Queen Victoria to European royal families and transmitted to her granddaughter, Russian Empress Alexandra and her son, Crown Prince Alexei. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19815722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Mutation Rate</em></strong></p><p>
|
|
In an analysis of 1,485 families with hemophilia A or hemophilia B, <a href="#4" class="mim-tip-reference" title="Barrai, I., Cann, H. M., Cavalli-Sforza, L. L., Barbujani, G., De Nicola, P. <strong>Segregation analysis of hemophilia A and B.</strong> Am. J. Hum. Genet. 37: 680-699, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9556658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9556658</a>]" pmid="9556658">Barrai et al. (1985)</a> estimated the proportion of sporadic cases to be 0.166 and 0.078, respectively. The age of maternal grandfathers at birth of the mother of hemophilia B cases was higher than that of appropriate controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9556658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the population of families with hemophilia B at the Malmo Haemophilia Centre, <a href="#87" class="mim-tip-reference" title="Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Kling, S., Nilsson, I. M., Giannelli, F. <strong>Direct estimate of the haemophilia B (factor IX deficiency) mutation rate and of the ratio of the sex-specific mutation rates in Sweden.</strong> Hum. Genet. 89: 319-322, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601423</a>] [<a href="https://doi.org/10.1007/BF00220550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1601423">Montandon et al. (1992)</a> estimated that the overall mutation rate was 4.1 x 10(-6) and that the ratio of male to female specific mutation rates was 11. Three of 13 isolated cases had a new mutation, whereas the other 10 had mothers who carried a new mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1601423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Kling, S., Ljung, R., Sjorin, E., Montandon, J., Green, P., Giannelli, F., Nilsson, I. M. <strong>Origin of mutation in sporadic cases of haemophilia-B.</strong> Europ. J. Haemat. 48: 142-145, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348478</a>] [<a href="https://doi.org/10.1111/j.1600-0609.1992.tb00585.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1348478">Kling et al. (1992)</a> found that 24 of 45 hemophilia B patients in Malmo, Sweden, had no affected family members. Three of 13 families with 1 patient available for study had a do novo mutation, whereas the defect was inherited from a carrier mother in the remaining 10. All 10 of these carrier mothers had de novo mutation, as their fathers were phenotypically normal and the grandmothers were noncarriers. In all 6 of the 10 cases in whom RFLP patterns were informative, the mutation was of paternal origin, and the average age of the father at the birth of the new carrier female was 41.5 years. These data supported a paternal age effect and a higher mutation rate in males than in females regarding factor IX mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 43 families with hemophilia B, <a href="#66" class="mim-tip-reference" title="Ketterling, R. P., Vielhaber, E., Bottema, C. D. K., Schaid, D. J., Cohen, M. P., Sexauer, C. L., Sommer, S. S. <strong>Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.</strong> Am. J. Hum. Genet. 52: 152-166, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434583</a>]" pmid="8434583">Ketterling et al. (1993)</a> found that 25 had a mutation in the female germline and 18 in the male germline. The excess of germline origins in females did not imply an overall excess mutation rate per basepair, because when the mother and maternal grandparents were analyzed, the excess of X chromosomes in females, 4:1, skewed the data in favor of female origins. Bayesian analysis corrected for this bias and indicated that the 25:18 ratio actually represented a predominance of mutations in males. Transitions at the dinucleotide CpG, estimated to account for 36% of mutations in the F9 gene (<a href="#71" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S. <strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong> Am. J. Hum. Genet. 47: 202-217, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>]" pmid="2198809">Koeberl et al., 1990</a>), showed the most striking male predominance of mutation, 11:1. This finding was comparable with previous data suggesting that methylation at CpG dinucleotides is reduced or absent in the female germline (<a href="#29" class="mim-tip-reference" title="Driscoll, D. J., Migeon, B. R. <strong>Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations.</strong> Somat. Cell Molec. Genet. 16: 267-282, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1694309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1694309</a>] [<a href="https://doi.org/10.1007/BF01233363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1694309">Driscoll and Migeon, 1990</a>). This effect, rather than an increased number of replications in the male germ cells, likely accounted for the male excess. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8434583+1694309+2198809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In studies of the patterns of independent mutation resulting in hemophilia B in 127 Caucasian and 44 non-Caucasian patients, <a href="#45" class="mim-tip-reference" title="Gostout, B., Vielhaber, E., Ketterling, R. P., Yoon, H.-S., Bottema, C. D. K., Kasper, C. K., Koerper, M. A., Sommer, S. S. <strong>Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians.</strong> Hum. Molec. Genet. 2: 293-298, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499919</a>] [<a href="https://doi.org/10.1093/hmg/2.3.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499919">Gostout et al. (1993)</a> could find no differences, suggesting either predominance of endogenous processes or common mutagen exposure rather than mutagen exposure specifically associated with non-Caucasian status or non-Western life style. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499919" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#51" class="mim-tip-reference" title="Green, P. M., Saad, S., Lewis, C. M., Giannelli, F. <strong>Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.</strong> Am. J. Hum. Genet. 65: 1572-1579, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577910</a>] [<a href="https://doi.org/10.1086/302651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577910">Green et al. (1999)</a> conducted a population-based study of hemophilia B mutations in the United Kingdom in order to construct a national confidential database of mutations and pedigrees to be used for the provision of carrier and prenatal diagnoses based on mutation detection. This allowed the direct estimate of overall mutation rate, male mutation rate, and female mutation rate for hemophilia B. The values obtained per gamete per generation and the 95% confidence intervals were 7.73 (6.29-9.12) x 10(-6) for overall mutation rate; 18.8 (14.5-22.9) x 10(-6) for male mutation rate; and 2.18 (1.44-3.16) x 10(-6) for female mutation rate. The ratio of male-to-female mutation rates was 8.64 (95% CI, 5.46-14.5). Attempts to detect evidence of gonadal mosaicism for hemophilia B mutation in suitable families did not detect any instances of ovarian mosaicism in 47 available opportunities. This suggested that the risk of a noncarrier mother manifesting as a gonadal mosaic by transmitting the mutation to a second child should be less than 0.062. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Giannelli, F., Anagnostopoulos, T., Green, P. M. <strong>Mutation rates in humans. II. Sporadic mutation-specific rates and rate of detrimental human mutations inferred from hemophilia B.</strong> Am. J. Hum. Genet. 65: 1580-1587, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577911</a>] [<a href="https://doi.org/10.1086/302652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577911">Giannelli et al. (1999)</a> also estimated the rates per base per generation of specific types of mutations, using their direct estimate of the overall mutation rate for hemophilia B and information on the mutations present in the U.K. population as well as those reported year by year in the hemophilia B world database. These rates were as follows: transitions at CpG sites, 9.7 x 10(-8); other transitions, 7.3 x 10(-9); transversions at CpG sites, 5.4 x 10(-9); other transversions, 6.9 x 10(-9); and small deletions/insertions causing frameshifts, 3.2 x 10(-10). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#68" class="mim-tip-reference" title="Ketterling, R. P., Vielhaber, E., Li, X., Drost, J., Schaid, D. J., Kasper, C. K., Phillips, J. A., III, Koerper, M. A., Kim, H., Sexauer, C., Gruppo, R., Ambriz, R., Paredes, R., Sommer, S. S. <strong>Germline origins in the human F9 gene: frequent G:C-to-A:T mosaicism and increased mutations with advanced maternal age.</strong> Hum. Genet. 105: 629-640, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10647899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10647899</a>] [<a href="https://doi.org/10.1007/s004399900158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10647899">Ketterling et al. (1999)</a> estimated the male:female ratio of mutations in the F9 gene by Bayesian analysis of 59 families. The overall ratio was estimated at 3.75. It varied with the type of mutation, from 6.65 and 6.10 for transitions at CpG and A:T to G:C transitions at non-CpG dinucleotides, respectively, to 0.57 and 0.42 for microdeletions/microinsertions and large deletions (more than 1 kb), respectively. The value for the 2 subsets of non-CpG transitions differed (6.10 for A:T to G:C vs 0.80 for G:C to A:T). Somatic mosaicism was detected in 11% of the 45 'origin individuals' for whom the causative mutation was visualized directly by genomic sequencing of leukocyte DNA (estimated sensitivity of approximately 1 part in 20). Four of the 5 defined somatic mosaics had G:C to A:T transitions at non-CpG dinucleotides, hinting that this mutation subtype may occur commonly early in embryogenesis. The age at conception was analyzed for 41 U.S. Caucasian families in which the age of the origin parent and the year of conception for the first carrier/hemophiliac were available. No evidence for a paternal age effect was seen; however, an advanced maternal age effect was observed (P = 0.03) and was particularly prominent in transversions. This suggested that an increased maternal age results in a higher rate of transmitted mutations, whereas the increased number of mitotic replications associated with advanced paternal age has little, if any, effect on the rate of transmitted mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10647899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#81" class="mim-tip-reference" title="Liu, J.-Z., Li, X., Drost, J., Thorland, E. C., Liu, Q., Lind, T., Roberts, S., Wang, H. Y., Sommer, S. S. <strong>The human factor IX gene as germline mutagen test: samples from mainland China have the putatively endogenous pattern of mutation.</strong> Hum. Mutat. 16: 31-36, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10874302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10874302</a>] [<a href="https://doi.org/10.1002/1098-1004(200007)16:1<31::AID-HUMU6>3.0.CO;2-I" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10874302">Liu et al. (2000)</a> found that the pattern of germline mutations in 66 hemophilia B patients from mainland China was similar to that in U.S. Caucasians, blacks, and Mexican Hispanics. The existence of a ubiquitous mutagen or the possibility that multiple mutagens could produce the same pattern of mutation was considered unlikely; the findings were compatible with the inference that endogenous processes predominate in germline mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10874302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ljung, R., Petrini, P., Tengborn, L., Sjorin, E. <strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong> Brit. J. Haemat. 113: 81-86, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328285">Ljung et al. (2001)</a> found that the ratio of male to female mutation rates was 5:3 and that the overall mutation rate per gamete per generation was 5.4 x 10(-6). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="geneTherapy" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneTherapyFold" id="mimGeneTherapyToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneTherapyToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Therapy</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneTherapyFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#32" class="mim-tip-reference" title="Gerrard, A. J., Hudson, D. L., Brownlee, G. G., Watt, F. M. <strong>Towards gene therapy for haemophilia B using primary human keratinocytes.</strong> Nature Genet. 3: 180-183, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499952</a>] [<a href="https://doi.org/10.1038/ng0293-180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499952">Gerrard et al. (1993)</a> introduced a recombinant human F9 cDNA into cultured primary human keratinocytes by means of a defective retroviral vector. In tissue culture, transduced keratinocytes were found to secrete biologically active factor IX. After transplantation of these cells into nude mice, human factor IX was detected in the bloodstream in small quantities for 1 week. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#63" class="mim-tip-reference" title="Kay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B., Chew, A. J., Tai, S. J., Herzog, R. W., Arruda, V., Johnson, F., Scallan, C., Skarsgard, E., Flake, A. W., High, K. A. <strong>Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.</strong> Nature Genet. 24: 257-261, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700178</a>] [<a href="https://doi.org/10.1038/73464" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10700178">Kay et al. (2000)</a> initiated a clinical study of intramuscular injection of an AAV vector expressing human factor IX in adults with severe hemophilia B. The study had a dose-escalation design. Assessment in the first 3 patients of safety and gene transfer and expression showed no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against factor IX. By PCR and Southern blot analyses of muscle biopsies, <a href="#63" class="mim-tip-reference" title="Kay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B., Chew, A. J., Tai, S. J., Herzog, R. W., Arruda, V., Johnson, F., Scallan, C., Skarsgard, E., Flake, A. W., High, K. A. <strong>Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.</strong> Nature Genet. 24: 257-261, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700178</a>] [<a href="https://doi.org/10.1038/73464" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10700178">Kay et al. (2000)</a> found that the vector sequences were present in muscle, and demonstrated expression of factor IX by immunohistochemistry. They observed modest changes in clinical endpoints, including circulating levels of factor IX and frequency of factor IX protein infusion. The evidence of gene expression at low doses of vector suggested that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offered the possibility of converting severe hemophilia B to a milder form of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10700178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Manno, C. S., Chew, A. J., Hutchison, S., Larson, P. J., Herzog, R. W., Arruda, V. R., Tai, S. J., Ragni, M. V., Thompson, A., Ozelo, M., Couto, L. B., Leonard, D. G. B., Johnson, F. A., McClelland, A., Scallan, C., Skarsgard, E., Flake, A. W., Kay, M. A., High, K. A., Glader, B. <strong>AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.</strong> Blood 101: 2963-2972, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12515715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12515715</a>] [<a href="https://doi.org/10.1182/blood-2002-10-3296" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12515715">Manno et al. (2003)</a> investigated the safety of intramuscular injection of a recombinant AAV (rAAV) vector expressing factor IX in patients with hemophilia B. Muscle biopsies of injection sites performed 2 to 10 months after vector administration confirmed gene transfer as evidenced by Southern blot and transgene expression as evidenced by immunohistochemical staining. However, circulating levels of factor IX were less than 2% in all cases and less than 1% in most. <a href="#84" class="mim-tip-reference" title="Manno, C. S., Chew, A. J., Hutchison, S., Larson, P. J., Herzog, R. W., Arruda, V. R., Tai, S. J., Ragni, M. V., Thompson, A., Ozelo, M., Couto, L. B., Leonard, D. G. B., Johnson, F. A., McClelland, A., Scallan, C., Skarsgard, E., Flake, A. W., Kay, M. A., High, K. A., Glader, B. <strong>AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.</strong> Blood 101: 2963-2972, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12515715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12515715</a>] [<a href="https://doi.org/10.1182/blood-2002-10-3296" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12515715">Manno et al. (2003)</a> concluded that the results demonstrated the safety of intramuscular rAAV administration in humans in a manner similar to that used in mice and hemophilic dogs (Herzog et al. (<a href="#57" class="mim-tip-reference" title="Herzog, R. W., Hagstrom, J. N., Kung, S.-H., Tai, S. J., Wilson, J. M., Fisher, K. J., High, K. A. <strong>Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus.</strong> Proc. Nat. Acad. Sci. 94: 5804-5809, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9159155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9159155</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9159155[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.11.5804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9159155">1997</a>, <a href="#58" class="mim-tip-reference" title="Herzog, R. W., Yang, E. Y., Couto, L. B., Hagstrom, J. N., Elwell, D., Fields, P. A., Burton, M., Bellinger, D. A., Read, M. S., Brinkhous, K. M., Podsakoff, G. M., Nichols, T. C., Kurtzman, G. J., High, K. A. <strong>Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.</strong> Nature Med. 5: 56-63, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9883840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9883840</a>] [<a href="https://doi.org/10.1038/4743" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9883840">1999</a>)). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12515715+9159155+9883840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#90" class="mim-tip-reference" title="Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., O'Beirne, J., Smith, K., and 20 others. <strong>Adenovirus-associated virus vector-mediated gene transfer in hemophilia B.</strong> New Eng. J. Med. 365: 2357-2365, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22149959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22149959</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22149959[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/10.1056/NEJMoa1108046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22149959">Nathwani et al. (2011)</a> infused a single dose of a serotype-8-pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX transgene in a peripheral vein in 6 patients with severe hemophilia B (factor IX activity less than 1% of normal values). Study participants were enrolled in 1 of 3 cohorts, with 2 participants in each group, and given a high, intermediate, or low dose of vector. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. AAV-mediated expression of factor IX at 2 to 11% of normal levels was observed in all participants. Four of the 6 discontinued prophylaxis and remained free of spontaneous hemorrhage; in the other 2, the interval between prophylactic injections was increased. Of the 2 participants who received the high dose of vector, 1 had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid-specific T cells in peripheral blood; the other had a slight increase in liver enzyme levels, the cause of which was less clear. Each of these 2 participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained factor IX levels in the range of 3 to 11% of normal values. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22149959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="George, L. A., Sullivan, S. K., Giermasz, A., Rasko, J. E. J., Samelson-Jones, B. J., Ducore, J., Cuker, A., Sullivan, L. M., Majumdar, S., Teitel, J., McGuinn, C. E., Ragni, M. V., and 16 others. <strong>Hemophilia B gene therapy with a high-specific-activity factor IX variant.</strong> New Eng. J. Med. 377: 2215-2227, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29211678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29211678</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29211678[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/10.1056/NEJMoa1708538" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29211678">George et al. (2017)</a> infused a single-stranded AAV vector (known as SPK-9001) consisting of a bioengineered capsid, liver-specific promoter, and factor IX Padua (factor IX-R338L, <a href="/entry/300746#0112">300746.0112</a>) transgene at a dose of 5 x 10(11) vector genomes per kg of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. The naturally occurring gain-of-function factor IX-R338L results in specific activity that is 8 to 12 times as high as nonmutant factor IX. No serious adverse events occurred during or after vector infusion. Vector-derived factor IX coagulant activity was sustained in all the participants, with a mean (+/- SD) steady-state factor IX coagulant activity of 33.7 +/- 18.5% (range, 14-81). On cumulative follow-up of 492 weeks among all the participants (range in individual participants, 28-78 weeks), the annualized bleeding rate was significantly reduced (mean rate, 11.1 events per year (range, 0-48) before vector administration versus 0.4 events per year (range, 0-4) after administration; p = 0.02), as was factor use (mean dose, 2908 IU per kg (range, 0-8090) before vector administration versus 49.3 IU per kg (range, 0-376) after administration; p = 0.004). After vector administration, 8 of 10 participants did not use factor, and 9 of 10 did not have bleeds. An asymptomatic increase in liver enzyme levels developed in 2 participants and resolved with short-term prednisone treatment. <a href="#31" class="mim-tip-reference" title="George, L. A., Sullivan, S. K., Giermasz, A., Rasko, J. E. J., Samelson-Jones, B. J., Ducore, J., Cuker, A., Sullivan, L. M., Majumdar, S., Teitel, J., McGuinn, C. E., Ragni, M. V., and 16 others. <strong>Hemophilia B gene therapy with a high-specific-activity factor IX variant.</strong> New Eng. J. Med. 377: 2215-2227, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29211678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29211678</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29211678[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/10.1056/NEJMoa1708538" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29211678">George et al. (2017)</a> concluded that the transgene factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29211678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#99" class="mim-tip-reference" title="Pipe, S. W., Leebeek, F. W. G., Recht, M., Key, N. S., Castaman, G., Miesbach, W., Lattimore, S., Peerlinck, K., Van der Valk, P., Coppens, M., Kampmann, P., Meijer, K., and 26 others. <strong>Gene therapy with etranacogene dezaparvovec for hemophilia B.</strong> New Eng. J. Med. 388: 706-718, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36812434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36812434</a>] [<a href="https://doi.org/10.1056/NEJMoa2211644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36812434">Pipe et al. (2023)</a> reported the results of an open-label, phase 3 study, after a 6-month lead-in of factor IX prophylaxis, of a 1-time infusion of AAV5 vector expressing the Padua factor IX variant (etranacogene dezaparvovec, 2 x 10(13) genomic copies per kg body weight) to 54 men aged 19 to 75 years (mean age 41.5 years) with hemophilia B with factor IX activity less than 2% of normal, regardless of preexisting AAV5 neutralizing antibodies. The annualized bleeding rate decreased from 4.19 (95% CI, 3.22-5.45) during the lead-in period to 1.51 (95% CI, 0.81-2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36, demonstrating superiority of the gene therapy compared with the factor IX prophylaxis. Factor IX activity had increased from baseline by a mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment. Usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant (p less than 0.001 for all comparisons). Benefits and safety were observed in participants with pretreatment AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36812434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Cuker, A., Kavakli, K., Frenzel, L., Wang, J.-D., Astermark, J., Cerqueira, M. H., Iorio, A., Katsarou-Fasouli, O., Klamroth, R., Shapiro, A. D., Hermans, C., Ishiguro, A., and 12 others. <strong>Gene therapy with fidanacogene elaparvovec in adults with hemophilia B.</strong> New Eng. J. Med. 391: 1108-1118, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39321362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39321362</a>] [<a href="https://doi.org/10.1056/NEJMoa2302982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39321362">Cuker et al. (2024)</a> reported results of a phase 3 open-label study of fidanacogene elaparvovec, an AAV vector designed to deliver transgene production of factor IX Padua (FIX-R338L) for hemophilia B. Forty-five men aged 18 to 62 years (mean 33.2 years) with factor IX levels of 2% or less who had received at least 6 months of therapy with prophylactic factor IX concentrate were infused with a single dose of fidanacogene elaparvovec. Of the 45 participants, 44 completed at least 15 months of follow-up. The primary end point, tested for noninferiority, was the annualized bleeding rate (treated and untreated bleeding episodes) from week 12 to month 15 after treatment with fidanacogene elaparvovec as compared with the prophylaxis lead-in period. The annualized rate of bleeding for all bleeding episodes decreased by 71%, from 4.42 (95% confidence interval (CI), 1.80 to 7.05) at baseline to 1.28 (95% CI, 0.57 to 1.98) after gene therapy, a treatment difference of -3.15 episodes (95% CI, -5.46 to -0.83; p = 0.008). The authors concluded that this result showed the noninferiority and superiority of fidanacogene elaparvovec to prophylaxis. At 15 months, the mean factor IX activity was 26.9% (median, 22.9%; range, 1.9 to 119.0) by 1-stage SynthASil assay. A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days. No infusion-related serious adverse events, thrombotic events, development of factor IX inhibitors, or malignant conditions were observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39321362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#37" class="mim-tip-reference" title="Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G. <strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong> Nature 303: 181-182, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6843667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6843667</a>] [<a href="https://doi.org/10.1038/303181a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6843667">Giannelli et al. (1983)</a> stated that 798 cases of Christmas disease were known in the U.K., corresponding to a frequency of 1 in 30,000 males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6843667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#20" class="mim-tip-reference" title="Connor, J. M., Pettigrew, A. F., Hann, I. M., Forbes, C. D., Lowe, G. D. O., Affara, N. A. <strong>Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland.</strong> J. Med. Genet. 22: 441-446, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4078877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4078877</a>] [<a href="https://doi.org/10.1136/jmg.22.6.441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4078877">Connor et al. (1985)</a>, by total ascertainment, found 28 families with hemophilia B in the west of Scotland (prevalence = 1/26,870 males). Of 26 living obligate carriers, 42% were heterozygous for a TaqI polymorphism recognized by the factor IX genomic probe. Linkage disequilibrium was apparent for this RFLP and hemophilia B in the west of Scotland. This surprising finding suggested that some of these families might be related. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4078877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Soucie, J. M., Evatt, B., Jackson, D., Hemophilia Surveillance System Project Investigators. <strong>Occurrence of hemophilia in the United States.</strong> Am. J. Hemat. 59: 288-294, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9840909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9840909</a>] [<a href="https://doi.org/10.1002/(sici)1096-8652(199812)59:4<288::aid-ajh4>3.0.co;2-i" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9840909">Soucie et al. (1998)</a> studied the frequency of hemophilia A and hemophilia B in 6 U.S. states: Colorado, Georgia, Louisiana, Massachusetts, New York, and Oklahoma. The age-adjusted prevalence of hemophilia in all 6 states in 1994 was 13.4 cases per 100,000 males (10.5 hemophilia A and 2.9 hemophilia B). The prevalence by race/ethnicity was 13.2 cases per 100,000 white, 11.0% among African American, and 11.5% among Hispanic males. Application of age-specific prevalence rates from the 6 surveillance states to the U.S. population resulted in an estimated national population of 13,320 cases of hemophilia A and 3,640 cases of hemophilia B. For the 10-year period 1982 to 1991, the average incidence of hemophilia A and B in the 6 surveillance states was estimated to be 1 in 5,032 live male births. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9840909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#75" class="mim-tip-reference" title="Kundu, R. K., Sangiorgi, F., Wu, L.-Y., Kurachi, K., Anderson, W. F., Maxson, R., Gordon, E. M. <strong>Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice.</strong> Blood 92: 168-174, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9639513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9639513</a>]" pmid="9639513">Kundu et al. (1998)</a> generated a transgenic mouse model of hemophilia B by targeted disruption of the murine f9 gene. The tail bleeding time of hemizygous male mice was markedly prolonged compared with those of normal and carrier female litter mates. Seven of 19 affected male mice died of exsanguination after tail snipping, and 2 affected mice died of umbilical cord bleeding. Ten affected mice survived to 4 months of age. Aside from the factor IX defect, carrier female and hemizygous male mice had no liver pathology by histologic examination, were fertile, and transmitted the mutation in the expected mendelian frequency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9639513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#53" class="mim-tip-reference" title="Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K. <strong>Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.</strong> Thromb. Haemost. 82: 1270-1275, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544912</a>]" pmid="10544912">Gu et al. (1999)</a> found factor IX deficiency in 2 distinct dog breeds. In 1 breed, the disorder was associated with a large deletion mutation, spanning the entire 5-prime region of the F9 gene extending to exon 6. In the second breed, an insertion of approximately 5 kb disrupted exon 8. The insertion was associated with alternative splicing between a donor site 5-prime and acceptor site 3-prime to the normal exon 8 splice junction, with introduction of a new stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10544912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Brooks, M. B., Gu, W., Barnas, J. L., Ray, J., Ray, K. <strong>A line 1 insertion in the factor IX gene segregates with mild hemophilia B in dogs.</strong> Mammalian Genome 14: 788-795, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722728</a>] [<a href="https://doi.org/10.1007/s00335-003-2290-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722728">Brooks et al. (2003)</a> found that mild hemophilia B in a large pedigree of German wirehaired pointers was caused by a line-1 insertion in the factor IX gene. The insert could be traced through at least 5 generations and segregated with the hemophilia B phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In transgenic mice with the hemophilia B Leyden phenotype (-20T-A; <a href="/entry/300746#0001">300746.0001</a>), which usually show amelioration of the disorder after puberty, <a href="#76" class="mim-tip-reference" title="Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K. <strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[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.0902191106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19416882">Kurachi et al. (2009)</a> found that expression of different F9 minigenes with or without the age-related stability element (ASE) in the 5-prime untranslated region resulted in different disease course. Mice lacking the ASE failed to show the Leyden phenotype with only transient F9 expression at puberty, whereas mice with ASE showed normal and sustained pubertal F9 recovery. These changes were not sex-dependent, indicating that testosterone and androgen are not responsible. Further studies showed that the transcription factor Ets1 (<a href="/entry/164720">164720</a>) was the specific ASE-binding protein, and F9 expression was abolished by hypophysectomy, but restored with growth hormone (GH; <a href="/entry/139250">139250</a>) administration in both males and females. These results provided a molecular mechanism for the puberty-related Leyden phenotype. <a href="#76" class="mim-tip-reference" title="Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K. <strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[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.0902191106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19416882">Kurachi et al. (2009)</a> also generated transgenic mice expressing the Brandenberg F9 mutation (-26G-C; <a href="/entry/300746#0097">300746.0097</a>), which showed a severe phenotype without amelioration after puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19416882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Animal Studies of Gene Therapy</em></strong></p><p>
|
|
<a href="#16" class="mim-tip-reference" title="Busby, S., Kumar, A., Joseph, M., Halfpap, L., Insley, M., Berkner, K., Kurachi, K., Woodbury, R. <strong>Expression of active human factor IX in transfected cells.</strong> Nature 316: 271-273, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3894976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3894976</a>] [<a href="https://doi.org/10.1038/316271a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3894976">Busby et al. (1985)</a> transfected baby hamster kidney (BHK) cells with a plasmid containing a gene for human factor IX and a plasmid containing a selectable marker. The cells secreted material that these authors believed to be authentic factor IX. <a href="#2" class="mim-tip-reference" title="Armentano, D., Thompson, A. R., Darlington, G., Woo, S. L. C. <strong>Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: potential for gene therapy of hemophilia B.</strong> Proc. Nat. Acad. Sci. 87: 6141-6145, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385589</a>] [<a href="https://doi.org/10.1073/pnas.87.16.6141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2385589">Armentano et al. (1990)</a> used a recombinant retroviral factor to transfer the human factor IX gene into hepatocytes from 3-week old New Zealand white rabbits. The infected cells produced human factor IX that was indistinguishable from the enzyme derived from normal human plasma. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2385589+3894976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#19" class="mim-tip-reference" title="Choo, K. H., Raphael, K., McAdam, W., Peterson, M. G. <strong>Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.</strong> Nucleic Acids Res. 15: 871-884, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029708</a>] [<a href="https://doi.org/10.1093/nar/15.3.871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3029708">Choo et al. (1987)</a> introduced a full-length human factor IX cDNA containing all the natural mRNA sequences plus some flanking intron sequences combined with a metallothionein promoter. This DNA clone was microinjected into the pronuclei of fertilized murine eggs. The transgenic mice expressed high levels of mRNA, gamma-carboxylated and glycosylated protein, and biologic clotting activity that were indistinguishable from normal human plasma factor IX. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Armentano, D., Thompson, A. R., Darlington, G., Woo, S. L. C. <strong>Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: potential for gene therapy of hemophilia B.</strong> Proc. Nat. Acad. Sci. 87: 6141-6145, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385589</a>] [<a href="https://doi.org/10.1073/pnas.87.16.6141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2385589">Armentano et al. (1990)</a> used a recombinant retroviral factor to transfer the factor IX gene into hepatocytes from 3-week old New Zealand white rabbits. The infected cells produced human factor IX that was indistinguishable from the enzyme derived from normal human plasma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2385589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Axelrod, J. H., Read, M. S., Brinkhous, K. M., Verma, I. M. <strong>Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs.</strong> Proc. Nat. Acad. Sci. 87: 5173-5177, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2367529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2367529</a>] [<a href="https://doi.org/10.1073/pnas.87.13.5173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2367529">Axelrod et al. (1990)</a> demonstrated that primary skin fibroblasts from hemophilic dogs, transduced by recombinant retrovirus containing a canine factor IX cDNA, secreted high levels of biologically active canine factor IX into the medium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2367529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#128" class="mim-tip-reference" title="Yao, S.-N., Wilson, J. M., Nabel, E. G., Kurachi, S., Hachiya, H. L., Kurachi, K. <strong>Expression of human factor IX in rat capillary endothelial cells: toward somatic gene therapy for hemophilia B.</strong> Proc. Nat. Acad. Sci. 88: 8101-8105, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1896457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1896457</a>] [<a href="https://doi.org/10.1073/pnas.88.18.8101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1896457">Yao et al. (1991)</a> infected rat capillary endothelial cells (CECs) with a Moloney murine leukemia virus-derived retrovirus vector that contained human factor IX cDNA. They found that a single RNA transcript of 4.4 kb, predicted by the construct, and a recombinant factor IX of 68 kD identical to purified plasma factor IX were formed. The recombinant factor IX that was produced showed full clotting activity, demonstrating that CECs have an efficient mechanism for posttranslational modifications, including gamma-carboxylation, essential for its biologic activity. These results, in addition to other properties of the endothelium, suggested that CECs could serve as an efficient drug delivery vehicle producing factor IX for somatic gene therapy of hemophilia B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1896457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#64" class="mim-tip-reference" title="Kay, M. A., Rothenberg, S., Landen, C. N., Bellinger, D. A., Leland, F., Toman, C., Finegold, M., Thompson, A. R., Read, M. S., Brinkhous, K. M., Woo, S. L. C. <strong>In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs.</strong> Science 262: 117-119, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8211118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8211118</a>] [<a href="https://doi.org/10.1126/science.8211118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8211118">Kay et al. (1993)</a> developed a method for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, and showed that the method resulted in the persistent expression of exogenous genes. When canine factor IX cDNA was transduced directly into hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reduction of whole blood clotting time and partial thromboplastin time of the treated animals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8211118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#124" class="mim-tip-reference" title="Wang, L., Zoppe, M., Hackeng, T. M., Griffin, J. H., Lee, K.-F., Verma, I. M. <strong>A factor IX-deficient mouse model for hemophilia B gene therapy.</strong> Proc. Nat. Acad. Sci. 94: 11563-11566, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9326649[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.21.11563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9326649">Wang et al. (1997)</a> generated a mouse model in which the gene encoding factor IX was disrupted by homologous recombination. The nullizygous mice were devoid of factor IX antigen in plasma. Consistent with the bleeding disorder, the factor IX coagulant activities for wildtype, heterozygous, and homozygous mice were 92, 53, and less than 5%, respectively, in activated partial thromboplastin time assays. Plasma factor IX activity in the deficient -/- mice was restored by introducing wildtype murine factor IX gene via adenoviral vectors. Thus, these factor IX-deficient mice provided a useful animal model for gene therapy studies of hemophilia B. The factor IX-deficient mice showed extensive bleeding after clipping a portion of the tail and bled to death unless the wound was cauterized. Additionally, in contrast to the normal mice, they showed swollen extremities and extensive hemorrhagic lesions after trauma. Female homozygous -/- mice gave birth without complications. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Schnieke, A. E., Kind, A. J., Ritchie, W. A., Mycock, K., Scott, A. R., Ritchie, M., Wilmut, I., Colman, A., Campbell, K. H. S. <strong>Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts.</strong> Science 278: 2130-2133, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405350</a>] [<a href="https://doi.org/10.1126/science.278.5346.2130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9405350">Schnieke et al. (1997)</a> produced transgenic sheep carrying the human factor IX gene by nuclear transfer. Ovine primary fetal fibroblasts were cotransfected with a neomycin-resistance marker gene (neo) and a human coagulation factor IX genomic construct designed for expression of the encoded protein in sheep milk. Nuclear transfer to enucleated oocytes was performed using either cloned transfectant fibroblasts or a population of neomycin-resistant cells as donors. Six transgenic lambs were liveborn: 3 produced from cloned transfectant cells contained factor IX and neo transgenes, whereas 3 produced from the uncloned population contained the marker gene only. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9405350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Preclinical studies in mice and hemophilic dogs showed that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX into skeletal muscle results in sustained expression of factor IX at levels sufficient to correct the hemophilic phenotype (<a href="#57" class="mim-tip-reference" title="Herzog, R. W., Hagstrom, J. N., Kung, S.-H., Tai, S. J., Wilson, J. M., Fisher, K. J., High, K. A. <strong>Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus.</strong> Proc. Nat. Acad. Sci. 94: 5804-5809, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9159155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9159155</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9159155[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.11.5804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9159155">Herzog et al., 1997</a>; <a href="#58" class="mim-tip-reference" title="Herzog, R. W., Yang, E. Y., Couto, L. B., Hagstrom, J. N., Elwell, D., Fields, P. A., Burton, M., Bellinger, D. A., Read, M. S., Brinkhous, K. M., Podsakoff, G. M., Nichols, T. C., Kurtzman, G. J., High, K. A. <strong>Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.</strong> Nature Med. 5: 56-63, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9883840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9883840</a>] [<a href="https://doi.org/10.1038/4743" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9883840">Herzog et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9159155+9883840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#127" class="mim-tip-reference" title="Yant, S. R., Meuse, L., Chiu, W., Ivics, Z., Izsvak, Z., Kay, M. A. <strong>Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system.</strong> Nature Genet. 25: 35-41, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802653</a>] [<a href="https://doi.org/10.1038/75568" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802653">Yant et al. (2000)</a> described the successful use of transposon technology for the nonhomologous insertion of foreign genes into the genomes of adult mammals using naked DNA. <a href="#127" class="mim-tip-reference" title="Yant, S. R., Meuse, L., Chiu, W., Ivics, Z., Izsvak, Z., Kay, M. A. <strong>Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system.</strong> Nature Genet. 25: 35-41, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802653</a>] [<a href="https://doi.org/10.1038/75568" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802653">Yant et al. (2000)</a> showed that the 'Sleeping Beauty' transposase, the product of a synthetic transposable element, can efficiently insert transposon DNA into the mouse genome in approximately 5 to 6% of transfected mouse liver cells. Chromosomal transposition resulted in long-term expression (greater than 5 months) of human blood coagulation factor IX at levels that were therapeutic in a mouse model of hemophilia B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#79" class="mim-tip-reference" title="Li, H., Haurigot, V., Doyon, Y., Li, T., Wong, S. Y., Bhagwat, A. S., Malani, N., Anguela, X. M., Sharma, R., Ivanciu, L., Murphy, S. L., Finn, J. D., Khazi, F. R., Zhou, S., Paschon, D. E., Rebar, E. J., Bushman, F. D., Gregory, P. D., Holmes, M. C., High, K. A. <strong>In vivo genome editing restores haemostasis in a mouse model of haemophilia.</strong> Nature 475: 217-221, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21706032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21706032</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21706032[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/nature10177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21706032">Li et al. (2011)</a> showed that zinc finger nucleases are able to induce double-strand breaks efficiently when delivered directly to mouse liver and that, when codelivered with an appropriately designed gene targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the zinc finger nuclease-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of hemophilia B, and remained persistent after induced liver regeneration. Thus, <a href="#79" class="mim-tip-reference" title="Li, H., Haurigot, V., Doyon, Y., Li, T., Wong, S. Y., Bhagwat, A. S., Malani, N., Anguela, X. M., Sharma, R., Ivanciu, L., Murphy, S. L., Finn, J. D., Khazi, F. R., Zhou, S., Paschon, D. E., Rebar, E. J., Bushman, F. D., Gregory, P. D., Holmes, M. C., High, K. A. <strong>In vivo genome editing restores haemostasis in a mouse model of haemophilia.</strong> Nature 475: 217-221, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21706032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21706032</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21706032[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/nature10177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21706032">Li et al. (2011)</a> concluded that zinc finger nuclease-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21706032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Bernardi1985" class="mim-tip-reference" title="Bernardi, F., Del Senno, L., Barbieri, R., Buzzoni, D., Gambari, R., Marchetti, G., Conconi, F., Panicucci, F., Positano, M., Pitruzzello, S. <strong>Gene deletion in an Italian haemophilia B subject.</strong> J. Med. Genet. 22: 305-307, 1985.">Bernardi et al. (1985)</a>; <a href="#Blackburn1962" class="mim-tip-reference" title="Blackburn, E. K., Monaghan, J. H., Lederer, H., MacFie, J. M. <strong>Christmas disease associated with primary capillary abnormalities.</strong> Brit. Med. J. 1: 154-156, 1962.">Blackburn et al. (1962)</a>; <a href="#Brown1970" class="mim-tip-reference" title="Brown, P. E., Hougie, C., Roberts, H. R. <strong>The genetic heterogeneity of hemophilia B.</strong> New Eng. J. Med. 283: 61-64, 1970.">Brown et al. (1970)</a>; <a href="#Brownlee1988" class="mim-tip-reference" title="Brownlee, G. G. <strong>Haemophilia B: a review of patient defects, diagnosis with gene probes and prospects for gene therapy.</strong> Recent Adv. Haemat. 5: 251-265, 1988.">Brownlee (1988)</a>; <a href="#Chan1998" class="mim-tip-reference" title="Chan, V., Chan, V. W. Y., Yip, B., Chim, C. S., Chan, T. K. <strong>Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.</strong> Am. J. Hemat. 58: 72-76, 1998.">Chan et al. (1998)</a>; <a href="#Connor1986" class="mim-tip-reference" title="Connor, J. M., Pettigrew, A. F., Shiach, C., Hann, I. M., Lowe, G. D. O., Forbes, C. D. <strong>Application of three intragenic DNA polymorphisms for carrier detection in haemophilia B.</strong> J. Med. Genet. 23: 300-309, 1986.">Connor et al. (1986)</a>; <a href="#Crossley1990" class="mim-tip-reference" title="Crossley, M., Winship, P. R., Austen, D. E. G., Rizza, C. R., Brownlee, G. G. <strong>A less severe form of haemophilia B Leyden.</strong> Nucleic Acids Res. 18: 4633, 1990.">Crossley
|
|
et al. (1990)</a>; <a href="#Crossley1989" class="mim-tip-reference" title="Crossley, P. M., Winship, P. R., Black, A., Rizza, C. R., Brownlee, G. G. <strong>Unusual case of haemophilia B. (Letter)</strong> Lancet 333: 960 only, 1989. Note: Originally Volume 1.">Crossley et al. (1989)</a>; <a href="#Didisheim1962" class="mim-tip-reference" title="Didisheim, P., Vandervoort, R. L. E. <strong>Detection of carriers for factor IX (PTC) deficiency.</strong> Blood 20: 150-155, 1962.">Didisheim and Vandervoort
|
|
(1962)</a>; <a href="#Giannelli1992" class="mim-tip-reference" title="Giannelli, F., Saad, S., Montandon, A. J., Bentley, D. R., Green, P. M. <strong>A new strategy for the genetic counselling of diseases of marked mutational heterogeneity: haemophilia B as a model.</strong> J. Med. Genet. 29: 602-607, 1992.">Giannelli et al. (1992)</a>; <a href="#Girolami1980" class="mim-tip-reference" title="Girolami, A., Dal Bo Zanon, R., De Marco, L., Cappellato, G. <strong>Hemophilia B with associated factor VII deficiency: a distinct variant of hemophilia B with low factor VII activity and normal factor VII antigen.</strong> Blut 40: 267-273, 1980.">Girolami et al. (1980)</a>; <a href="#Goldsmith1979" class="mim-tip-reference" title="Goldsmith, J. C., Roer, M. E. S., Orringer, E. P. <strong>A new treatment strategy for hemophilia B: incorporation of factor IX into red cell ghosts.</strong> Am. J. Hemat. 7: 119-125, 1979.">Goldsmith et
|
|
al. (1979)</a>; <a href="#Green1989" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.">Green et al. (1989)</a>; <a href="#Green1993" class="mim-tip-reference" title="Green, P. M., Mitchell, V. E., McGraw, A., Goldman, E., Giannelli, F. <strong>Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.</strong> Hum. Mutat. 2: 103-107, 1993.">Green et al. (1993)</a>; <a href="#Green1991" class="mim-tip-reference" title="Green, P. M., Montandon, A. J., Ljung, R., Bentley, D. R., Nilsson, I.-M., Kling, S., Giannelli, F. <strong>Haemophilia B mutations in a complete Swedish population sample: a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity.</strong> Brit. J. Haemat. 78: 390-397, 1991.">Green et al.
|
|
(1991)</a>; <a href="#Grunebaum1984" class="mim-tip-reference" title="Grunebaum, L., Cazenave, J.-P., Camerino, G., Kloepfer, C., Mandel, J. L., Tolstoshev, P., Jaye, M., de la Salle, H., Lecocq, J. P. <strong>Carrier detection of haemophilia B by using a restriction site polymorphism associated with the coagulation factor IX gene.</strong> J. Clin. Invest. 73: 1491-1495, 1984.">Grunebaum et al. (1984)</a>; <a href="#Hay1986" class="mim-tip-reference" title="Hay, C. W., Robertson, K. A., Yong, S.-L., Thompson, A. R., Growe, G. H., MacGillivray, R. T. A. <strong>Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status.</strong> Blood 67: 1508-1511, 1986.">Hay et al. (1986)</a>; <a href="#Hirosawa1990" class="mim-tip-reference" title="Hirosawa, S., Fahner, J. B., Salier, J.-P., Wu, C.-T., Lovrien, E. W., Kurachi, K. <strong>Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.</strong> Proc. Nat. Acad. Sci. 87: 4421-4425, 1990.">Hirosawa et al.
|
|
(1990)</a>; <a href="#Holmberg1980" class="mim-tip-reference" title="Holmberg, L., Gustavii, B., Cordesius, E., Kristoffersson, A.-C., Ljung, R., Lofberg, L., Stromberg, P., Nilsson, I. M. <strong>Prenatal diagnosis of hemophilia B by an immunoradiometric assay of factor IX.</strong> Blood 56: 397-401, 1980.">Holmberg et al. (1980)</a>; <a href="#Kasper1977" class="mim-tip-reference" title="Kasper, C. K., Osterud, B., Minami, J. Y., Schonick, W., Rapaport, S. I. <strong>Hemophilia B--characterization of genetic variants and detection of carriers.</strong> Blood 50: 351-366, 1977.">Kasper et al. (1977)</a>; <a href="#Ketterling1991" class="mim-tip-reference" title="Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S. <strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong> Hum. Genet. 87: 333-337, 1991.">Ketterling et
|
|
al. (1991)</a>; <a href="#Kitchens1976" class="mim-tip-reference" title="Kitchens, C. S., Levin, J., Smith, W. K. <strong>Hemorrhagic diathesis in a carrier of hemophilia B.</strong> Am. J. Med. 60: 138-143, 1976.">Kitchens et al. (1976)</a>; <a href="#Koeberl1990" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Sommer, S. S. <strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong> Am. J. Med. Genet. 35: 600-608, 1990.">Koeberl et al. (1990)</a>; <a href="#Lillicrap1986" class="mim-tip-reference" title="Lillicrap, D. P., Liddell, M. B., Matthews, R. J., Peake, I. R., Bloom, A. L. <strong>Comparison of phenotypic assessment and the use of two restriction fragment length polymorphisms in the diagnosis of the carrier state in haemophilia B.</strong> Brit. J. Haemat. 62: 557-565, 1986.">Lillicrap
|
|
et al. (1986)</a>; <a href="#Montandon1990" class="mim-tip-reference" title="Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Nilsson, I. M., Giannelli, F. <strong>Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD).</strong> Hum. Genet. 85: 200-204, 1990.">Montandon et al. (1990)</a>; <a href="#Neal1973" class="mim-tip-reference" title="Neal, W. R., Tayloe, D. T., Jr., Cederbaum, A. I., Roberts, H. R. <strong>Detection of genetic variants of haemophilia B with an immunosorbent technique.</strong> Brit. J. Haemat. 25: 63-68, 1973.">Neal et al. (1973)</a>; <a href="#Neuschatz1973" class="mim-tip-reference" title="Neuschatz, J., Necheles, T. F. <strong>Hemophilia B in a phenotypically normal girl with XX (ring): XO mosaicism.</strong> Acta Haemat. 49: 108-113, 1973.">Neuschatz
|
|
and Necheles (1973)</a>; <a href="#Orstavik1985" class="mim-tip-reference" title="Orstavik, K. H., Stormorken, H., Sparr, T. <strong>Hemophilia B(M) in a female.</strong> Thromb. Res. 37: 561-566, 1985.">Orstavik et al. (1985)</a>; <a href="#Orstavik1979" class="mim-tip-reference" title="Orstavik, K. H., Veltkamp, J. J., Bertina, R. M., Hermans, J. <strong>Detection of carriers of haemophilia B.</strong> Brit. J. Haemat. 42: 293-301, 1979.">Orstavik et al. (1979)</a>; <a href="#Peake1989" class="mim-tip-reference" title="Peake, I. R., Matthews, R. J., Bloom, A. L. <strong>Haemophilia B Chicago: severe haemophilia B caused by two deletions and an inversion within the factor IX gene.</strong> Brit. J. Haemat. 71 (suppl. 1): 1, 1989.">Peake et al. (1989)</a>; <a href="#Poort1989" class="mim-tip-reference" title="Poort, S. R., Briet, E., Bertina, R. M., Reitsma, P. H. <strong>A Dutch pedigree with mild hemophilia B with a missense mutation in the first EGF domain [factor IX(Oud en Nieuw Gastel)].</strong> Nucleic Acids Res. 17: 5869, 1989.">Poort et al. (1989)</a>; <a href="#Tanimoto1988" class="mim-tip-reference" title="Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H. <strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong> J. Lab. Clin. Med. 112: 307-313, 1988.">Tanimoto et al. (1988)</a>; <a href="#Taylor1991" class="mim-tip-reference" title="Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P. <strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong> Proc. Nat. Acad. Sci. 88: 39-42, 1991.">Taylor et al. (1991)</a>; <a href="#Vidaud1993" class="mim-tip-reference" title="Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M. <strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong> Hum. Genet. 91: 241-244, 1993.">Vidaud et al. (1993)</a>; <a href="#Wall1967" class="mim-tip-reference" title="Wall, R. L., McConnell, J., Moore, D., Macpherson, C. R., Marson, A. <strong>Christmas disease, color-blindness and blood group Xg(a).</strong> Am. J. Med. 43: 214-226, 1967.">Wall et al. (1967)</a>; <a href="#Whittaker1962" class="mim-tip-reference" title="Whittaker, D. L., Copeland, D. L., Graham, J. B. <strong>Linkage of color blindness with hemophilias A and B.</strong> Am. J. Hum. Genet. 14: 149-158, 1962.">Whittaker et al. (1962)</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="Aggeler1952" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aggeler, P. M., White, S. G., Glendening, M. B., Page, E. W., Leake, T. B., Bates, G.
|
|
<strong>Plasma thromboplastin component (PTC) deficiency: a new disease resembling hemophilia.</strong>
|
|
Proc. Soc. Exp. Biol. Med. 79: 692-694, 1952.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14920537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14920537</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14920537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3181/00379727-79-19488" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Armentano1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Armentano, D., Thompson, A. R., Darlington, G., Woo, S. L. C.
|
|
<strong>Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: potential for gene therapy of hemophilia B.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 6141-6145, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2385589" 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.87.16.6141" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Axelrod1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Axelrod, J. H., Read, M. S., Brinkhous, K. M., Verma, I. M.
|
|
<strong>Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 5173-5177, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2367529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2367529</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2367529" 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.87.13.5173" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Barrai1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barrai, I., Cann, H. M., Cavalli-Sforza, L. L., Barbujani, G., De Nicola, P.
|
|
<strong>Segregation analysis of hemophilia A and B.</strong>
|
|
Am. J. Hum. Genet. 37: 680-699, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9556658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9556658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9556658" 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="Bernardi1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernardi, F., Del Senno, L., Barbieri, R., Buzzoni, D., Gambari, R., Marchetti, G., Conconi, F., Panicucci, F., Positano, M., Pitruzzello, S.
|
|
<strong>Gene deletion in an Italian haemophilia B subject.</strong>
|
|
J. Med. Genet. 22: 305-307, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4045960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4045960</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4045960" 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.22.4.305" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bertina1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Briet, E., Veltkamp, J. J.
|
|
<strong>Variants of vitamin K dependent coagulation factors. (Editorial)</strong>
|
|
Acta Haemat. 62: 1-3, 1979.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bertina1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Veltkamp, J. J.
|
|
<strong>The abnormal factor IX of hemophilia B+ variants.</strong>
|
|
Thromb. Haemost. 40: 335-349, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/734633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">734633</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=734633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Biggs1952" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R.
|
|
<strong>Christmas disease: a condition previously mistaken for haemophilia.</strong>
|
|
Brit. Med. J. 2: 1378-1382, 1952.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12997790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12997790</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12997790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.2.4799.1378" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Blackburn1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blackburn, E. K., Monaghan, J. H., Lederer, H., MacFie, J. M.
|
|
<strong>Christmas disease associated with primary capillary abnormalities.</strong>
|
|
Brit. Med. J. 1: 154-156, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13869677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13869677</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13869677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.1.5272.154" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Bottema1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Sommer, S. S.
|
|
<strong>Direct carrier testing in 14 families with haemophilia B.</strong>
|
|
Lancet 334: 526-529, 1989. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2570235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2570235</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2570235" 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(89)90653-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Briet1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Briet, E., Bertina, R. M., van Tilburg, N. H., Veltkamp, J. J.
|
|
<strong>Hemophilia B Leyden: a sex-linked hereditary disorder that improves after puberty.</strong>
|
|
New Eng. J. Med. 306: 788-790, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7062952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7062952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7062952" 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/NEJM198204013061306" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Brinkhous1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brinkhous, K. M., Davis, P. D., Graham, J. B., Dodds, W. J.
|
|
<strong>Expression and linkage of genes for X-linked hemophilias A and B in the dog.</strong>
|
|
Blood 41: 577-585, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4688873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4688873</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4688873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Brooks2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brooks, M. B., Gu, W., Barnas, J. L., Ray, J., Ray, K.
|
|
<strong>A line 1 insertion in the factor IX gene segregates with mild hemophilia B in dogs.</strong>
|
|
Mammalian Genome 14: 788-795, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722728</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722728" 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/s00335-003-2290-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Brown1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, P. E., Hougie, C., Roberts, H. R.
|
|
<strong>The genetic heterogeneity of hemophilia B.</strong>
|
|
New Eng. J. Med. 283: 61-64, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5420360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5420360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5420360" 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/NEJM197007092830203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Brownlee1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brownlee, G. G.
|
|
<strong>Haemophilia B: a review of patient defects, diagnosis with gene probes and prospects for gene therapy.</strong>
|
|
Recent Adv. Haemat. 5: 251-265, 1988.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Busby1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Busby, S., Kumar, A., Joseph, M., Halfpap, L., Insley, M., Berkner, K., Kurachi, K., Woodbury, R.
|
|
<strong>Expression of active human factor IX in transfected cells.</strong>
|
|
Nature 316: 271-273, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3894976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3894976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3894976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/316271a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Chan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, V. W. Y., Yip, B., Chim, C. S., Chan, T. K.
|
|
<strong>Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.</strong>
|
|
Am. J. Hemat. 58: 72-76, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590153" 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/(sici)1096-8652(199805)58:1<72::aid-ajh13>3.0.co;2-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Chen1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Yoshitake, S., Chance, P. F., Bray, G. L., Thompson, A. R., Scott, C. R., Kurachi, K.
|
|
<strong>An intragenic deletion of the factor IX gene in a family with hemophilia B.</strong>
|
|
J. Clin. Invest. 76: 2161-2164, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3001143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3001143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001143" 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/JCI112222" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Choo1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Choo, K. H., Raphael, K., McAdam, W., Peterson, M. G.
|
|
<strong>Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.</strong>
|
|
Nucleic Acids Res. 15: 871-884, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029708" 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/nar/15.3.871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Connor1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Connor, J. M., Pettigrew, A. F., Hann, I. M., Forbes, C. D., Lowe, G. D. O., Affara, N. A.
|
|
<strong>Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland.</strong>
|
|
J. Med. Genet. 22: 441-446, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4078877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4078877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4078877" 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.22.6.441" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Connor1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Connor, J. M., Pettigrew, A. F., Shiach, C., Hann, I. M., Lowe, G. D. O., Forbes, C. D.
|
|
<strong>Application of three intragenic DNA polymorphisms for carrier detection in haemophilia B.</strong>
|
|
J. Med. Genet. 23: 300-309, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3018248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3018248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3018248" 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.23.4.300" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Costa2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M.
|
|
<strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong>
|
|
Blood 96: 1585-1587, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Crossley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crossley, M., Winship, P. R., Austen, D. E. G., Rizza, C. R., Brownlee, G. G.
|
|
<strong>A less severe form of haemophilia B Leyden.</strong>
|
|
Nucleic Acids Res. 18: 4633, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2388855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2388855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2388855" 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/nar/18.15.4633" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Crossley1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crossley, P. M., Winship, P. R., Black, A., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Unusual case of haemophilia B. (Letter)</strong>
|
|
Lancet 333: 960 only, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2565449" 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(89)92540-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Cuker2024" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cuker, A., Kavakli, K., Frenzel, L., Wang, J.-D., Astermark, J., Cerqueira, M. H., Iorio, A., Katsarou-Fasouli, O., Klamroth, R., Shapiro, A. D., Hermans, C., Ishiguro, A., and 12 others.
|
|
<strong>Gene therapy with fidanacogene elaparvovec in adults with hemophilia B.</strong>
|
|
New Eng. J. Med. 391: 1108-1118, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39321362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39321362</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39321362" 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/NEJMoa2302982" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Cutler2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F.
|
|
<strong>Germline mosaicism resulting in the transmission of severe hemophilia B from a grandfather with a mild deficiency.</strong>
|
|
Am. J. Med. Genet. 129A: 13-15, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266608</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.30162" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Denson1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Denson, K. W., Biggs, P., Mannucci, P. M.
|
|
<strong>An investigation of three patients with Christmas disease due to an abnormal type of factor IX.</strong>
|
|
J. Clin. Path. 21: 160-165, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4972271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4972271</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4972271" 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/jcp.21.2.160" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Didisheim1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Didisheim, P., Vandervoort, R. L. E.
|
|
<strong>Detection of carriers for factor IX (PTC) deficiency.</strong>
|
|
Blood 20: 150-155, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13886232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13886232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13886232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Driscoll1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Driscoll, D. J., Migeon, B. R.
|
|
<strong>Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations.</strong>
|
|
Somat. Cell Molec. Genet. 16: 267-282, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1694309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1694309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1694309" 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/BF01233363" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="George1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, J. N., Miller, G. M., Breckenridge, R. T.
|
|
<strong>Studies on Christmas disease: investigation and treatment of a familial acquired inhibitor of factor IX.</strong>
|
|
Brit. J. Haemat. 21: 333-342, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4998792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4998792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4998792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1971.tb03445.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="George2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, L. A., Sullivan, S. K., Giermasz, A., Rasko, J. E. J., Samelson-Jones, B. J., Ducore, J., Cuker, A., Sullivan, L. M., Majumdar, S., Teitel, J., McGuinn, C. E., Ragni, M. V., and 16 others.
|
|
<strong>Hemophilia B gene therapy with a high-specific-activity factor IX variant.</strong>
|
|
New Eng. J. Med. 377: 2215-2227, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29211678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29211678</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29211678[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=29211678" 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/NEJMoa1708538" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Gerrard1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gerrard, A. J., Hudson, D. L., Brownlee, G. G., Watt, F. M.
|
|
<strong>Towards gene therapy for haemophilia B using primary human keratinocytes.</strong>
|
|
Nature Genet. 3: 180-183, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499952" 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/ng0293-180" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Ghosh2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ghosh, K., Shankarkumar, U., Shetty, S., Mohanty, D.
|
|
<strong>Chronic synovitis and HLA B27 in patients with severe haemophilia.</strong>
|
|
Lancet 361: 933-934, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12648975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12648975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12648975" 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(03)12763-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Giangrande2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giangrande, P. L. F.
|
|
<strong>Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors.</strong>
|
|
Brit. J. Haemat. 121: 703-712, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12780784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12780784</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12780784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2003.04333.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Giannelli1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Anagnostopoulos, T., Green, P. M.
|
|
<strong>Mutation rates in humans. II. Sporadic mutation-specific rates and rate of detrimental human mutations inferred from hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1580-1587, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302652" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Giannelli1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Anson, D. S., Choo, K. H., Rees, D. J. G., Winship, P. R., Ferrari, N., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency).</strong>
|
|
Lancet 323: 239-241, 1984. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6142992" 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)90122-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Giannelli1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong>
|
|
Nature 303: 181-182, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6843667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6843667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6843667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/303181a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Giannelli1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Lillicrap, D. P., Ludwig, M., Olek, K., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--third edition, 1992.</strong>
|
|
Nucleic Acids Res. 20: 2027-2063, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1598234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1598234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1598234" 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/nar/20.suppl.2027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Giannelli1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993.</strong>
|
|
Nucleic Acids Res. 21: 3075-3087, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8392713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8392713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8392713" 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/nar/21.13.3075" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Giannelli1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.</strong>
|
|
Nucleic Acids Res. 24: 103-118, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8594556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8594556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8594556" 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/nar/24.1.103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Giannelli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Figueiredo, M. S., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions, 7th edition.</strong>
|
|
Nucleic Acids Res. 25: 133-135, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9016521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9016521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9016521" 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/nar/25.1.133" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Giannelli1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Saad, S., Montandon, A. J., Bentley, D. R., Green, P. M.
|
|
<strong>A new strategy for the genetic counselling of diseases of marked mutational heterogeneity: haemophilia B as a model.</strong>
|
|
J. Med. Genet. 29: 602-607, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1404290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1404290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1404290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.29.9.602" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Girolami1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Girolami, A., Dal Bo Zanon, R., De Marco, L., Cappellato, G.
|
|
<strong>Hemophilia B with associated factor VII deficiency: a distinct variant of hemophilia B with low factor VII activity and normal factor VII antigen.</strong>
|
|
Blut 40: 267-273, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7370439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7370439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7370439" 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/BF01080186" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Goldsmith1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goldsmith, J. C., Roer, M. E. S., Orringer, E. P.
|
|
<strong>A new treatment strategy for hemophilia B: incorporation of factor IX into red cell ghosts.</strong>
|
|
Am. J. Hemat. 7: 119-125, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/539589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">539589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=539589" 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/ajh.2830070204" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Gostout1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gostout, B., Vielhaber, E., Ketterling, R. P., Yoon, H.-S., Bottema, C. D. K., Kasper, C. K., Koerper, M. A., Sommer, S. S.
|
|
<strong>Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians.</strong>
|
|
Hum. Molec. Genet. 2: 293-298, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499919</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499919" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/2.3.293" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Green1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Bentley, D. R., Mibashan, R. S., Giannelli, F.
|
|
<strong>Partial deletion by illegitimate recombination of the factor IX gene in a haemophilia B family with two inhibitor patients.</strong>
|
|
Molec. Biol. Med. 5: 95-106, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3398774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3398774</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3398774" 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="Green1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F.
|
|
<strong>Molecular pathology of haemophilia B.</strong>
|
|
EMBO J. 8: 1067-1072, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Green1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Mitchell, V. E., McGraw, A., Goldman, E., Giannelli, F.
|
|
<strong>Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.</strong>
|
|
Hum. Mutat. 2: 103-107, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8318985" 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.1380020207" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Green1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Montandon, A. J., Bentley, D. R., Giannelli, F.
|
|
<strong>Genetics and molecular biology of haemophilias A and B.</strong>
|
|
Blood Coagul. Fibrinolysis 2: 539-565, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1768766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1768766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1768766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00001721-199108000-00007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Green1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Montandon, A. J., Ljung, R., Bentley, D. R., Nilsson, I.-M., Kling, S., Giannelli, F.
|
|
<strong>Haemophilia B mutations in a complete Swedish population sample: a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity.</strong>
|
|
Brit. J. Haemat. 78: 390-397, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1873221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1873221</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1873221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1991.tb04453.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Green1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Saad, S., Lewis, C. M., Giannelli, F.
|
|
<strong>Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1572-1579, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577910</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302651" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Grunebaum1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grunebaum, L., Cazenave, J.-P., Camerino, G., Kloepfer, C., Mandel, J. L., Tolstoshev, P., Jaye, M., de la Salle, H., Lecocq, J. P.
|
|
<strong>Carrier detection of haemophilia B by using a restriction site polymorphism associated with the coagulation factor IX gene.</strong>
|
|
J. Clin. Invest. 73: 1491-1495, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6325506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6325506</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6325506" 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/JCI111354" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Gu1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K.
|
|
<strong>Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.</strong>
|
|
Thromb. Haemost. 82: 1270-1275, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10544912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Hashmi1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hashmi, K. Z., MacIver, J. E., Delamore, I. W.
|
|
<strong>Christmas disease in a female.</strong>
|
|
Lancet 312: 965-966, 1978. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/81989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">81989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=81989" 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(78)92528-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Hassan1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hassan, H. J., Leonardi, A., Guerriero, R., Chelucci, C., Cianetti, L., Ciavarella, N., Ranieri, P., Pilolli, D., Peschle, C.
|
|
<strong>Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.</strong>
|
|
Blood 66: 728-730, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2992643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2992643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2992643" 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="56" class="mim-anchor"></a>
|
|
<a id="Hay1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hay, C. W., Robertson, K. A., Yong, S.-L., Thompson, A. R., Growe, G. H., MacGillivray, R. T. A.
|
|
<strong>Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status.</strong>
|
|
Blood 67: 1508-1511, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3008893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3008893</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3008893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Herzog1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Herzog, R. W., Hagstrom, J. N., Kung, S.-H., Tai, S. J., Wilson, J. M., Fisher, K. J., High, K. A.
|
|
<strong>Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 5804-5809, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9159155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9159155</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9159155[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=9159155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.94.11.5804" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Herzog1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Herzog, R. W., Yang, E. Y., Couto, L. B., Hagstrom, J. N., Elwell, D., Fields, P. A., Burton, M., Bellinger, D. A., Read, M. S., Brinkhous, K. M., Podsakoff, G. M., Nichols, T. C., Kurtzman, G. J., High, K. A.
|
|
<strong>Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.</strong>
|
|
Nature Med. 5: 56-63, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9883840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9883840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9883840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/4743" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Hirosawa1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hirosawa, S., Fahner, J. B., Salier, J.-P., Wu, C.-T., Lovrien, E. W., Kurachi, K.
|
|
<strong>Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 4421-4425, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2352926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2352926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2352926" 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.87.12.4421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Holmberg1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Gustavii, B., Cordesius, E., Kristoffersson, A.-C., Ljung, R., Lofberg, L., Stromberg, P., Nilsson, I. M.
|
|
<strong>Prenatal diagnosis of hemophilia B by an immunoradiometric assay of factor IX.</strong>
|
|
Blood 56: 397-401, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7407407/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7407407</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7407407" 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="Hougie1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hougie, C., Twomey, J. J.
|
|
<strong>Hemophilia B(M): a new type of factor-IX deficiency.</strong>
|
|
Lancet 289: 698-700, 1967. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4163943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4163943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4163943" 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(67)92179-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Kasper1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kasper, C. K., Osterud, B., Minami, J. Y., Schonick, W., Rapaport, S. I.
|
|
<strong>Hemophilia B--characterization of genetic variants and detection of carriers.</strong>
|
|
Blood 50: 351-366, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/884315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">884315</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=884315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Kay2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B., Chew, A. J., Tai, S. J., Herzog, R. W., Arruda, V., Johnson, F., Scallan, C., Skarsgard, E., Flake, A. W., High, K. A.
|
|
<strong>Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.</strong>
|
|
Nature Genet. 24: 257-261, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10700178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/73464" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Kay1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kay, M. A., Rothenberg, S., Landen, C. N., Bellinger, D. A., Leland, F., Toman, C., Finegold, M., Thompson, A. R., Read, M. S., Brinkhous, K. M., Woo, S. L. C.
|
|
<strong>In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs.</strong>
|
|
Science 262: 117-119, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8211118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8211118</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8211118" 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.8211118" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Ketterling1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S.
|
|
<strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong>
|
|
Hum. Genet. 87: 333-337, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864609</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1864609" 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/BF00200915" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Ketterling1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Bottema, C. D. K., Schaid, D. J., Cohen, M. P., Sexauer, C. L., Sommer, S. S.
|
|
<strong>Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.</strong>
|
|
Am. J. Hum. Genet. 52: 152-166, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434583" 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="67" class="mim-anchor"></a>
|
|
<a id="Ketterling1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E. L., Lind, T. J., Thorland, E. C., Sommer, S. S.
|
|
<strong>The rates and patterns of deletions in the human factor IX gene.</strong>
|
|
Am. J. Hum. Genet. 54: 201-213, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8304338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8304338</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8304338" 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="68" class="mim-anchor"></a>
|
|
<a id="Ketterling1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Li, X., Drost, J., Schaid, D. J., Kasper, C. K., Phillips, J. A., III, Koerper, M. A., Kim, H., Sexauer, C., Gruppo, R., Ambriz, R., Paredes, R., Sommer, S. S.
|
|
<strong>Germline origins in the human F9 gene: frequent G:C-to-A:T mosaicism and increased mutations with advanced maternal age.</strong>
|
|
Hum. Genet. 105: 629-640, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10647899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10647899</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10647899" 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/s004399900158" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Kitchens1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kitchens, C. S., Levin, J., Smith, W. K.
|
|
<strong>Hemorrhagic diathesis in a carrier of hemophilia B.</strong>
|
|
Am. J. Med. 60: 138-143, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1082713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1082713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1082713" 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(76)90542-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Kling1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kling, S., Ljung, R., Sjorin, E., Montandon, J., Green, P., Giannelli, F., Nilsson, I. M.
|
|
<strong>Origin of mutation in sporadic cases of haemophilia-B.</strong>
|
|
Europ. J. Haemat. 48: 142-145, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348478" 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.1600-0609.1992.tb00585.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Koeberl1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S.
|
|
<strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong>
|
|
Am. J. Hum. Genet. 47: 202-217, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2198809" 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="72" class="mim-anchor"></a>
|
|
<a id="Koeberl1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sarkar, G., Ketterling, R. P., Chen, S.-H., Sommer, S. S.
|
|
<strong>Recurrent nonsense mutations at arginine residues cause severe hemophilia B in unrelated hemophiliacs.</strong>
|
|
Hum. Genet. 84: 387-390, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1969838" 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/BF00195805" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Koeberl1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sommer, S. S.
|
|
<strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong>
|
|
Am. J. Med. Genet. 35: 600-608, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970704</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1970704" 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.1320350435" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Krepischi-Santos2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Krepischi-Santos, A. C. V., Carneiro, J. D. A., Svartman, M., Bendit, I., Odone-Filho, V., Vianna-Morgante, A. M.
|
|
<strong>Deletion of the factor IX gene as a result of translocation t(X;1) in a girl affected by haemophilia B.</strong>
|
|
Brit. J. Haemat. 113: 616-620, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11380446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11380446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11380446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2001.02786.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Kundu1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kundu, R. K., Sangiorgi, F., Wu, L.-Y., Kurachi, K., Anderson, W. F., Maxson, R., Gordon, E. M.
|
|
<strong>Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice.</strong>
|
|
Blood 92: 168-174, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9639513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9639513</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9639513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Kurachi2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K.
|
|
<strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[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=19416882" 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.0902191106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Lascari1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lascari, A. D., Hoak, J. C., Taylor, J. C.
|
|
<strong>Christmas disease in a girl.</strong>
|
|
Am. J. Dis. Child. 117: 585-588, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5781711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5781711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5781711" 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.1969.02100030587016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Lefkowitz1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R.
|
|
<strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong>
|
|
Am. J. Hemat. 43: 177-182, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8352232" 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/ajh.2830430304" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Li2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, H., Haurigot, V., Doyon, Y., Li, T., Wong, S. Y., Bhagwat, A. S., Malani, N., Anguela, X. M., Sharma, R., Ivanciu, L., Murphy, S. L., Finn, J. D., Khazi, F. R., Zhou, S., Paschon, D. E., Rebar, E. J., Bushman, F. D., Gregory, P. D., Holmes, M. C., High, K. A.
|
|
<strong>In vivo genome editing restores haemostasis in a mouse model of haemophilia.</strong>
|
|
Nature 475: 217-221, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21706032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21706032</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21706032[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=21706032" 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/nature10177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Lillicrap1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lillicrap, D. P., Liddell, M. B., Matthews, R. J., Peake, I. R., Bloom, A. L.
|
|
<strong>Comparison of phenotypic assessment and the use of two restriction fragment length polymorphisms in the diagnosis of the carrier state in haemophilia B.</strong>
|
|
Brit. J. Haemat. 62: 557-565, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3006741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3006741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3006741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1986.tb02968.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Liu2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, J.-Z., Li, X., Drost, J., Thorland, E. C., Liu, Q., Lind, T., Roberts, S., Wang, H. Y., Sommer, S. S.
|
|
<strong>The human factor IX gene as germline mutagen test: samples from mainland China have the putatively endogenous pattern of mutation.</strong>
|
|
Hum. Mutat. 16: 31-36, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10874302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10874302</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10874302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1098-1004(200007)16:1<31::AID-HUMU6>3.0.CO;2-I" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Ljung2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ljung, R., Petrini, P., Tengborn, L., Sjorin, E.
|
|
<strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong>
|
|
Brit. J. Haemat. 113: 81-86, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Mandalaki1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mandalaki, T., Louizou, C., Dimitriadou, C., Briet, E.
|
|
<strong>Haemophilia B Leyden in Greece.</strong>
|
|
Thromb. Haemost. 56: 340-342, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3563965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3563965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3563965" 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="Manno2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Manno, C. S., Chew, A. J., Hutchison, S., Larson, P. J., Herzog, R. W., Arruda, V. R., Tai, S. J., Ragni, M. V., Thompson, A., Ozelo, M., Couto, L. B., Leonard, D. G. B., Johnson, F. A., McClelland, A., Scallan, C., Skarsgard, E., Flake, A. W., Kay, M. A., High, K. A., Glader, B.
|
|
<strong>AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.</strong>
|
|
Blood 101: 2963-2972, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12515715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12515715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12515715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2002-10-3296" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Matthews1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L.
|
|
<strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong>
|
|
J. Clin. Invest. 79: 746-753, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029178" 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/JCI112880" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Matthews1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Peake, I. R., Bloom, A. L., Anson, D. S.
|
|
<strong>Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene.</strong>
|
|
J. Med. Genet. 25: 779-780, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907054</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2907054" 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.25.11.779" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Montandon1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Kling, S., Nilsson, I. M., Giannelli, F.
|
|
<strong>Direct estimate of the haemophilia B (factor IX deficiency) mutation rate and of the ratio of the sex-specific mutation rates in Sweden.</strong>
|
|
Hum. Genet. 89: 319-322, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1601423" 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/BF00220550" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Montandon1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Nilsson, I. M., Giannelli, F.
|
|
<strong>Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD).</strong>
|
|
Hum. Genet. 85: 200-204, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2370049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2370049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2370049" 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/BF00193196" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Montandon1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Giannelli, F., Bentley, D. R.
|
|
<strong>Direct detection of point mutations by mismatch analysis: application to haemophilia B.</strong>
|
|
Nucleic Acids Res. 17: 3347-3358, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2726481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2726481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2726481" 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/nar/17.9.3347" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Nathwani2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., O'Beirne, J., Smith, K., and 20 others.
|
|
<strong>Adenovirus-associated virus vector-mediated gene transfer in hemophilia B.</strong>
|
|
New Eng. J. Med. 365: 2357-2365, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22149959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22149959</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22149959[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=22149959" 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/NEJMoa1108046" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Neal1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Neal, W. R., Tayloe, D. T., Jr., Cederbaum, A. I., Roberts, H. R.
|
|
<strong>Detection of genetic variants of haemophilia B with an immunosorbent technique.</strong>
|
|
Brit. J. Haemat. 25: 63-68, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4793126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4793126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4793126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1973.tb01716.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Neuschatz1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Neuschatz, J., Necheles, T. F.
|
|
<strong>Hemophilia B in a phenotypically normal girl with XX (ring): XO mosaicism.</strong>
|
|
Acta Haemat. 49: 108-113, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4196476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4196476</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4196476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000208391" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Nisen1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nisen, P., Stamberg, J., Ehrenpreis, R., Velasco, S., Shende, A., Engelberg, J., Karayalcin, G., Waber, L.
|
|
<strong>The molecular basis of severe hemophilia B in a girl.</strong>
|
|
New Eng. J. Med. 315: 1139-1142, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3093864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3093864</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3093864" 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/NEJM198610303151806" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Nour-Eldin1959" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nour-Eldin, F., Wilkinson, J. F.
|
|
<strong>Factor-VII deficiency with Christmas disease in one family.</strong>
|
|
Lancet 273: 1173-1176, 1959. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13666001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13666001</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13666001" 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(59)91184-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Orstavik1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orstavik, K. H., Stormorken, H., Sparr, T.
|
|
<strong>Hemophilia B(M) in a female.</strong>
|
|
Thromb. Res. 37: 561-566, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3983911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3983911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3983911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0049-3848(85)90088-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Orstavik1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orstavik, K. H., Veltkamp, J. J., Bertina, R. M., Hermans, J.
|
|
<strong>Detection of carriers of haemophilia B.</strong>
|
|
Brit. J. Haemat. 42: 293-301, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/465373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">465373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=465373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1979.tb01133.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Peake1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Furlong, B. L., Bloom, A. L.
|
|
<strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong>
|
|
Lancet 323: 242-243, 1984. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6142993" 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)90123-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Peake1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Matthews, R. J., Bloom, A. L.
|
|
<strong>Haemophilia B Chicago: severe haemophilia B caused by two deletions and an inversion within the factor IX gene.</strong>
|
|
Brit. J. Haemat. 71 (suppl. 1): 1, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Pipe2023" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pipe, S. W., Leebeek, F. W. G., Recht, M., Key, N. S., Castaman, G., Miesbach, W., Lattimore, S., Peerlinck, K., Van der Valk, P., Coppens, M., Kampmann, P., Meijer, K., and 26 others.
|
|
<strong>Gene therapy with etranacogene dezaparvovec for hemophilia B.</strong>
|
|
New Eng. J. Med. 388: 706-718, 2023.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36812434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36812434</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36812434" 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/NEJMoa2211644" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Plug2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Plug, I., Mauser-Bunschoten, E. P., Brocker-Vriends, A. H. J. T., van Amstel, H. K. P., van der Bom, J. G., van Diemen-Homan, J. E. M., Willemse, J., Rosendaal, F. R.
|
|
<strong>Bleeding in carriers of hemophilia.</strong>
|
|
Blood 108: 52-56, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16551972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16551972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16551972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2005-09-3879" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Poon1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poon, M.-C., Chui, D. H. K., Patterson, M., Starozik, D. M., Dimnik, L. S., Hoar, D. I.
|
|
<strong>Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes.</strong>
|
|
J. Clin. Invest. 79: 1204-1209, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2881949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2881949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2881949" 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/JCI112938" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Poort1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poort, S. R., Briet, E., Bertina, R. M., Reitsma, P. H.
|
|
<strong>A Dutch pedigree with mild hemophilia B with a missense mutation in the first EGF domain [factor IX(Oud en Nieuw Gastel)].</strong>
|
|
Nucleic Acids Res. 17: 5869, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2762170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2762170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2762170" 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/nar/17.14.5869" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Purrello1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Purrello, M., Alhadeff, B., Esposito, D., Szabo, P., Rocchi, M., Truett, M., Masiarz, F., Siniscalco, M.
|
|
<strong>The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.</strong>
|
|
EMBO J. 4: 725-729, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3924593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3924593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3924593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1985.tb03689.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Reitsma1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E.
|
|
<strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong>
|
|
Blood 72: 1074, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3416069" 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="Roberts1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roberts, H. R., Grizzle, J. E., McLester, W. D., Penick, G. D.
|
|
<strong>Genetic variants of hemophilia B: detection by means of a specific PTC inhibitor.</strong>
|
|
J. Clin. Invest. 47: 360-365, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12066779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12066779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12066779" 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/JCI105732" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Rogaev2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rogaev, E. I., Grigorenko, A. P., Faskhutdinova, G., Kittler, E. L. W., Moliaka, Y. K.
|
|
<strong>Genotype analysis identifies the cause of the 'Royal disease.'</strong>
|
|
Science 326: 817 only, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19815722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19815722</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19815722" 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.1180660" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Schnieke1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schnieke, A. E., Kind, A. J., Ritchie, W. A., Mycock, K., Scott, A. R., Ritchie, M., Wilmut, I., Colman, A., Campbell, K. H. S.
|
|
<strong>Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts.</strong>
|
|
Science 278: 2130-2133, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9405350" 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.278.5346.2130" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="108" class="mim-anchor"></a>
|
|
<a id="Siguret1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Siguret, V., Amselem, S., Vidaud, M., Assouline, Z., Kerbiriou-Nabias, D., Pietu, G., Goossens, M., Larrieu, M. J., Bahnak, B., Meyer, D., Lavergne, J. M.
|
|
<strong>Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.</strong>
|
|
Brit. J. Haemat. 70: 411-416, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3219291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3219291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3219291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1988.tb02509.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Sommer1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sommer, S. S., Bowie, E. J. W., Ketterling, R. P., Bottema, C. D. K.
|
|
<strong>Missense mutations and the magnitude of functional deficit: the example of factor IX.</strong>
|
|
Hum. Genet. 89: 295-297, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1601420" 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/BF00220543" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="110" class="mim-anchor"></a>
|
|
<a id="Soucie1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Soucie, J. M., Evatt, B., Jackson, D., Hemophilia Surveillance System Project Investigators.
|
|
<strong>Occurrence of hemophilia in the United States.</strong>
|
|
Am. J. Hemat. 59: 288-294, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9840909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9840909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9840909" 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/(sici)1096-8652(199812)59:4<288::aid-ajh4>3.0.co;2-i" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Spinelli1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spinelli, A., Schmid, W., Straub, P. W.
|
|
<strong>Christmas disease (haemophilia B) in a girl with deletion of the short arm of one X-chromosome (functional Turner syndrome).</strong>
|
|
Brit. J. Haemat. 34: 129-135, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/952762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">952762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=952762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1976.tb00181.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Szabo1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Szabo, P., Purrello, M., Rocchi, M., Archidiacono, N., Alhadeff, B., Filippi, G., Toniolo, D., Martini, G., Luzzatto, L., Siniscalco, M.
|
|
<strong>Cytological mapping of the human glucose-6-phosphate dehydrogenase gene distal to the fragile-X site suggests a high rate of meiotic recombination across this site.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 7855-7859, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6595664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6595664</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6595664" 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.81.24.7855" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="113" class="mim-anchor"></a>
|
|
<a id="Tanimoto1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H.
|
|
<strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong>
|
|
J. Lab. Clin. Med. 112: 307-313, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3411192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3411192</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3411192" 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="114" class="mim-anchor"></a>
|
|
<a id="Taylor1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P.
|
|
<strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong>
|
|
Proc. Nat. Acad. Sci. 88: 39-42, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1986380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1986380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1986380" 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.88.1.39" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="115" class="mim-anchor"></a>
|
|
<a id="Taylor1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Duffin, J., Cameron, C., Teitel, J., Garvey, B., Lillicrap, D. P.
|
|
<strong>Characterization of the original Christmas disease mutation (cysteine 206-to-serine): from clinical recognition to molecular pathogenesis.</strong>
|
|
Thromb. Haemost. 67: 63-65, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1615485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1615485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1615485" 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="116" class="mim-anchor"></a>
|
|
<a id="Taylor1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N.
|
|
<strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong>
|
|
Hum. Genet. 79: 273-276, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841226</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2841226" 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/BF00366250" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="117" class="mim-anchor"></a>
|
|
<a id="Veltkamp1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A.
|
|
<strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong>
|
|
Scand. J. Haemat. 7: 82-90, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5450691" 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.1600-0609.1970.tb01873.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="118" class="mim-anchor"></a>
|
|
<a id="Verstraete1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verstraete, M., Vermylen, C., Vandenbroucke, J.
|
|
<strong>Hemophilia B associated with a decreased factor VII activity.</strong>
|
|
Am. J. Med. Sci. 243: 20-26, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13925578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13925578</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13925578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00000441-196201000-00003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="119" class="mim-anchor"></a>
|
|
<a id="Vianna-Morgante1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vianna-Morgante, A. M., Batista, D. A. S., Levisky, R. B., Zatz, M.
|
|
<strong>X;autosome translocations in females with X-linked recessive diseases. (Abstract)</strong>
|
|
7th International Congress of Human Genetics, Berlin 1986. P. 97.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="120" class="mim-anchor"></a>
|
|
<a id="Vidaud1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M.
|
|
<strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong>
|
|
Hum. Genet. 91: 241-244, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8478007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8478007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8478007" 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/BF00218264" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="121" class="mim-anchor"></a>
|
|
<a id="Wadelius1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wadelius, C., Blomback, M., Pettersson, U.
|
|
<strong>Molecular studies of haemophilia B in Sweden: identification of patients with total deletion of the factor IX gene and without inhibitory antibodies.</strong>
|
|
Hum. Genet. 81: 13-17, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2848757" 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/BF00283721" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="122" class="mim-anchor"></a>
|
|
<a id="Wadelius1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wadelius, C., Lindstedt, M., Pigg, M., Egberg, N., Pettersson, U., Anvret, M.
|
|
<strong>Hemophilia B in a 46,XX female probably caused by non-random X inactivation.</strong>
|
|
Clin. Genet. 43: 1-4, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8096443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8096443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8096443" 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.1399-0004.1993.tb04415.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="123" class="mim-anchor"></a>
|
|
<a id="Wall1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wall, R. L., McConnell, J., Moore, D., Macpherson, C. R., Marson, A.
|
|
<strong>Christmas disease, color-blindness and blood group Xg(a).</strong>
|
|
Am. J. Med. 43: 214-226, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5298508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5298508</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5298508" 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(67)90166-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="124" class="mim-anchor"></a>
|
|
<a id="Wang1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, L., Zoppe, M., Hackeng, T. M., Griffin, J. H., Lee, K.-F., Verma, I. M.
|
|
<strong>A factor IX-deficient mouse model for hemophilia B gene therapy.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 11563-11566, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9326649[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=9326649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.94.21.11563" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="125" class="mim-anchor"></a>
|
|
<a id="Whittaker1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whittaker, D. L., Copeland, D. L., Graham, J. B.
|
|
<strong>Linkage of color blindness with hemophilias A and B.</strong>
|
|
Am. J. Hum. Genet. 14: 149-158, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14006651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14006651</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14006651" 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="126" class="mim-anchor"></a>
|
|
<a id="Winship1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Winship, P. R., Rees, D. J. G., Alkan, M.
|
|
<strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong>
|
|
Lancet 333: 631-634, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2564457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2564457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2564457" 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(89)92141-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="127" class="mim-anchor"></a>
|
|
<a id="Yant2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yant, S. R., Meuse, L., Chiu, W., Ivics, Z., Izsvak, Z., Kay, M. A.
|
|
<strong>Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system.</strong>
|
|
Nature Genet. 25: 35-41, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/75568" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="128" class="mim-anchor"></a>
|
|
<a id="Yao1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yao, S.-N., Wilson, J. M., Nabel, E. G., Kurachi, S., Hachiya, H. L., Kurachi, K.
|
|
<strong>Expression of human factor IX in rat capillary endothelial cells: toward somatic gene therapy for hemophilia B.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 8101-8105, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1896457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1896457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1896457" 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.88.18.8101" 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">
|
|
Ada Hamosh - updated : 10/16/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 03/09/2023<br>Ada Hamosh - updated : 01/23/2018<br>Ada Hamosh - updated : 9/8/2014<br>Ada Hamosh - updated : 8/24/2011<br>Ada Hamosh - updated : 12/29/2009<br>Cassandra L. Kniffin - updated : 11/25/2009<br>Cassandra L. Kniffin - updated : 12/3/2008<br>Cassandra L. Kniffin - reorganized : 10/21/2008<br>Cassandra L. Kniffin - updated : 11/13/2007<br>Victor A. McKusick - updated : 1/11/2005<br>Victor A. McKusick - updated : 4/22/2004<br>Victor A. McKusick - updated : 9/4/2003<br>Victor A. McKusick - updated : 7/18/2003<br>Ada Hamosh - updated : 9/12/2002<br>Victor A. McKusick - updated : 9/20/2001<br>Victor A. McKusick - updated : 6/26/2001<br>Victor A. McKusick - updated : 6/22/2001<br>Victor A. McKusick - updated : 1/10/2001<br>Victor A. McKusick - updated : 9/22/2000<br>Victor A. McKusick - updated : 8/17/2000<br>Ada Hamosh - updated : 4/28/2000<br>Victor A. McKusick - updated : 3/1/2000<br>Victor A. McKusick - updated : 1/14/2000<br>Victor A. McKusick - updated : 1/13/2000<br>Victor A. McKusick - updated : 12/20/1999<br>Ada Hamosh - updated : 7/28/1999<br>Victor A. McKusick - updated : 2/14/1999<br>Victor A. McKusick - updated : 8/17/1998<br>Victor A. McKusick - updated : 7/13/1998<br>Victor A. McKusick - updated : 12/18/1997<br>Victor A. McKusick - updated : 11/6/1997<br>Victor A. McKusick - updated : 9/16/1997<br>Victor A. McKusick - updated : 3/21/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 10/16/2024
|
|
</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 : 03/10/2023<br>alopez : 03/09/2023<br>alopez : 01/23/2018<br>carol : 10/17/2016<br>carol : 11/06/2014<br>alopez : 9/8/2014<br>alopez : 9/8/2014<br>terry : 2/29/2012<br>terry : 1/18/2012<br>alopez : 8/25/2011<br>terry : 8/24/2011<br>carol : 4/11/2011<br>carol : 4/7/2011<br>alopez : 1/5/2010<br>terry : 12/29/2009<br>wwang : 12/2/2009<br>carol : 12/2/2009<br>ckniffin : 11/25/2009<br>ckniffin : 11/25/2009<br>terry : 6/5/2009<br>terry : 4/9/2009<br>terry : 4/9/2009<br>wwang : 12/4/2008<br>ckniffin : 12/3/2008<br>terry : 11/19/2008<br>carol : 10/21/2008<br>ckniffin : 10/15/2008<br>carol : 10/9/2008<br>terry : 8/26/2008<br>wwang : 11/20/2007<br>ckniffin : 11/13/2007<br>carol : 11/27/2006<br>terry : 11/10/2005<br>wwang : 1/14/2005<br>wwang : 1/12/2005<br>terry : 1/11/2005<br>terry : 4/22/2004<br>alopez : 4/7/2004<br>carol : 3/17/2004<br>cwells : 9/30/2003<br>terry : 9/4/2003<br>tkritzer : 7/29/2003<br>terry : 7/18/2003<br>carol : 7/7/2003<br>alopez : 9/12/2002<br>cwells : 9/12/2002<br>mcapotos : 1/2/2002<br>mcapotos : 9/27/2001<br>terry : 9/20/2001<br>mcapotos : 7/5/2001<br>mcapotos : 7/5/2001<br>mcapotos : 6/26/2001<br>terry : 6/26/2001<br>terry : 6/22/2001<br>mcapotos : 3/27/2001<br>cwells : 1/17/2001<br>terry : 1/10/2001<br>mcapotos : 10/3/2000<br>mcapotos : 9/22/2000<br>carol : 8/18/2000<br>terry : 8/17/2000<br>alopez : 5/1/2000<br>terry : 4/28/2000<br>alopez : 3/1/2000<br>terry : 3/1/2000<br>mgross : 2/21/2000<br>terry : 1/14/2000<br>terry : 1/13/2000<br>carol : 12/27/1999<br>terry : 12/20/1999<br>terry : 9/21/1999<br>alopez : 7/30/1999<br>carol : 7/28/1999<br>kayiaros : 7/8/1999<br>kayiaros : 7/8/1999<br>carol : 2/14/1999<br>carol : 2/5/1999<br>psherman : 1/8/1999<br>dkim : 12/15/1998<br>dkim : 12/10/1998<br>dkim : 9/22/1998<br>dkim : 9/22/1998<br>carol : 8/18/1998<br>terry : 8/17/1998<br>dkim : 7/21/1998<br>carol : 7/16/1998<br>terry : 7/13/1998<br>alopez : 5/21/1998<br>mark : 12/18/1997<br>terry : 12/16/1997<br>terry : 11/13/1997<br>terry : 11/6/1997<br>mark : 9/22/1997<br>terry : 9/16/1997<br>terry : 9/16/1997<br>alopez : 7/29/1997<br>alopez : 7/8/1997<br>terry : 5/28/1997<br>terry : 3/21/1997<br>terry : 3/17/1997<br>mark : 11/12/1996<br>terry : 10/24/1996<br>mark : 7/22/1996<br>mark : 7/9/1996<br>mark : 3/30/1996<br>terry : 3/12/1996<br>mark : 12/20/1995<br>jason : 7/19/1994<br>carol : 5/23/1994<br>terry : 4/26/1994<br>warfield : 4/20/1994<br>mimadm : 4/15/1994<br>pfoster : 4/5/1994
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>#</strong> 306900
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HEMOPHILIA B; HEMB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CHRISTMAS DISEASE<br />
|
|
FACTOR IX DEFICIENCY<br />
|
|
F9 DEFICIENCY<br />
|
|
PLASMA THROMBOPLASTIN COMPONENT DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
HEMOPHILIA B(M), INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
HEMOPHILIA B LEYDEN, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 41788008, 767712006;
|
|
|
|
|
|
<strong>ICD10CM:</strong> D67;
|
|
|
|
|
|
<strong>ICD9CM:</strong> 286.1;
|
|
|
|
|
|
<strong>ORPHA:</strong> 169793, 169796, 169799, 177929, 98879;
|
|
|
|
|
|
<strong>DO:</strong> 12259;
|
|
|
|
|
|
</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">
|
|
Xq27.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hemophilia B
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
306900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
F9
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300746
|
|
</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 hemophilia B (HEMB), also known as Christmas disease, is caused by mutation in the gene encoding coagulation factor IX (F9; 300746).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hemophilia B (HEMB), which results from factor IX deficiency, is phenotypically indistinguishable from hemophilia A (306700), which results from coagulation factor VIII (F8; 300841) deficiency. The classic laboratory findings in hemophilia B include a prolonged activated partial thromboplastin time (aPTT) and a normal prothrombin time (PT) (Lefkowitz et al., 1993). </p><p>Early studies made a distinction between cross-reactive-material (CRM)-negative and CRM-positive hemophilia B mutants. This classification referred to detection of the F9 antigen in plasma, even in the presence of decreased F9 activity. Detection of the antigen indicated the presence of a dysfunctional F9 protein. Roberts et al. (1968) found that about 90% of patients with hemophilia B were CRM-negative, whereas about 10% were CRM-positive. However, Bertina and Veltkamp (1978) found that a rather large proportion of the hemophilia B patients could be characterized as hemophilia B CRM+. They identified 14 cases of hemophilia B CRM+ from 11 families among a group of 33 patients. After immunologic and activity comparisons, they found at least 7 different factor IX variants. Bertina and Veltkamp (1978) noted the high heterogeneity within this group. In an editorial on variants of vitamin K-dependent coagulation factors, Bertina et al. (1979) stated that 9 defective variants of factor II, 5 variants of factor X, and many variants (about 180 pedigrees) of factor IX had been identified. At least one variant of factor VII (Padua) was also known. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Aggeler et al. (1952) described a 16-year-old white male with a hemophilia-like disorder in which there appeared to be a deficiency of a coagulation factor, which the authors called 'plasma thromboplastin component' (PTC). They cited reports indicating that blood from some patients with hemophilia was capable of correcting the coagulation defect in other cases of hemophilia in vitro. The authors concluded that these patients had a combined defect of PTC deficiency and 'true' hemophilia (hemophilia A). It was not clear at that time if the disorder was hereditary. </p><p>Biggs et al. (1952) in the December 27 (Christmas) issue of the British Medical Journal reported a 5-year-old boy, with a surname of 'Christmas' who had this disorder, as well as other patients, some of whom came from families showing a typical X-linked pattern of inheritance, Biggs et al. (1952) defended the familial eponym in the following way: 'The naming of clinical disorders after patients was introduced by Sir Jonathan Hutchinson and is now familiar from serological research; it has the advantage that no hypothetical implication is attached to such a name.' Giangrande (2003) provided historical information concerning the patient Stephen Christmas (1947-1993), whose mutation in the F9 gene (300746.0109) was reported by Taylor et al. (1992) and his physicians. </p><p><strong><em>Hemophilia B(M)</em></strong></p><p>
|
|
A subset of hemophilia B patients have a prolonged prothrombin time when exposed to bovine (or ox) brain tissue, which serves as a source of thromboplastin, or tissue factor (F3; 134390); these CRM+ patients are classified as having hemophilia B(M) (Lefkowitz et al., 1993). </p><p>Several workers (e.g., Nour-Eldin and Wilkinson, 1959) observed the combination of factor IX deficiency with factor VII (F7; 613878) deficiency. However, inheritance was always X-linked, even though F7 is on chromosome 13. Verstraete et al. (1962) reported 4 families in which all affected males had both Christmas disease and factor VII deficiency. The authors suggested that factor VII deficiency was a consistent secondary phenomenon; thus no separate mutation for the combined defect would be necessary. </p><p>Hougie and Twomey (1967) defined a variant of hemophilia B that differed from the usual form by the presence of a prolonged PT. They presented evidence these patients had a structurally abnormal and inactive form of factor IX that acted as an inhibitor of the normal reaction between factor VII and bovine brain. They called the variant hemophilia B(M), after the initial of the family surname. </p><p>Denson et al. (1968) identified 3 blood samples of hemophilia B(M) among samples derived from 27 patients with Christmas disease. In a series of coagulation assays, Denson et al. (1968) demonstrated that the prolongation of the PT involved inhibition of the reaction between ox brain tissue factor, factor VII, and factor X. Noting that this distinct abnormality had only been observed in patients with factor IX deficiency, the authors postulated that the 'inhibitor' may be an abnormal protein similar to or identical with factor IX. Subsequent studies showed that this inhibitor was an abnormal form of factor IX that was functionally inactive but was antigenically indistinguishable from normal factor IX. </p><p>Lefkowitz et al. (1993) noted that the bovine brain tissue in studies of hemophilia B(M) is the source of thromboplastin, or tissue factor (F3; 134390); PT times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. However, in various studies of factor IX Hilo (300746.0031), Lefkowitz et al. (1993) found that either normal F9 or Hilo F9 prolonged the PT regardless of the tissue factor source, but the prolongation required high concentrations of factor IX when rabbit or human brain was used. With bovine thromboplastin, factor IX Hilo was significantly better than normal factor IX at prolonging the PT. In addition, the prolongation times depended on the amounts of factors IX and X used in the assays. </p><p><strong><em>Hemophilia B Leyden</em></strong></p><p>
|
|
Veltkamp et al. (1970) described a variant of hemophilia B, termed hemophilia B Leyden, in a Dutch family. The disorder was characterized by the disappearance of the bleeding diathesis as the patient aged. In affected individuals, plasma factor IX levels were less than 1% of normal before puberty, but after puberty factor IX activity and antigen levels rose steadily in a 1:1 ratio to a maximum of 50 to 60%. </p><p>Briet et al. (1982) described a similar variant of hemophilia B that took a severe form early in life but remitted after puberty, with an increase in factor IX levels from below 1% of normal to about 50% of normal by age 80 years. Three pedigrees with 27 affected males with this disorder could be traced to a small village in the east of the Netherlands. </p><p>In affected members of 2 Dutch pedigrees with hemophilia B Leyden, Reitsma et al. (1988) found that patients with hemophilia B Leyden had a mutation in the promoter region of the F9 gene (300746.0001). The findings suggested that a point mutation could lead to a switch from constitutive to steroid hormone-dependent gene expression. The families were probably related. </p><p>Mandalaki et al. (1986) reported a 5-generation Greek family with hemophilia B. The factor IX levels in the 3 patients from the last generation were extremely low, while those of patients in the older generations were much higher. In 1 patient, the rise of factor IX levels appeared between ages 13 and 14 years. In addition, older patients in the family had much milder symptoms compared to the younger patients. The phenotype was similar to hemophilia B Leyden as described by Veltkamp et al. (1970). </p><p><strong><em>Manifesting Females</em></strong></p><p>
|
|
Lascari et al. (1969) described a daughter of a male with hemophilia B who had an XX karyotype, factor IX level of 5%, and hemarthrosis. The factor IX level in the mother was 100%. The girl was thought to be a manifesting heterozygote with unfortunate lyonization. </p><p>Spinelli et al. (1976) observed deletion of the short arm of 1 of the X chromosomes in a female with hemophilia B. Family investigations were negative. Hashmi et al. (1978) reported a girl with Christmas disease. Her father was affected, and her parents were related as first cousins, suggesting possible homozygosity for the defect. They referred to a similar instance of plausible homozygosity. </p><p>Wadelius et al. (1993) reported a female with hemophilia B with factor IX activity of about 1%. Her father had severe hemophilia B. No chromosomal abnormality could be detected, and DNA analysis gave no indication of deletions or mutations of TaqI cleavage sites in the F9 gene. Analysis of the methylation pattern of locus DXS255 indicated that the expression of hemophilia B in this girl was caused by nonrandom X inactivation. </p><p>Vianna-Morgante et al. (1986) observed de novo t(X;1)(q27;q23) in a girl with hemophilia B who had no affected relatives. In a full description of the case, Krepischi-Santos et al. (2001) stated that the translocated X was preferentially active and that methylation analysis of the DXS255 locus confirmed the skewed X inactivation with the paternal allele being the active one. Molecular analysis showed deletion of at least part of the F9 gene. </p><p>Nisen et al. (1986) described hemophilia B in a girl with the karyotype 46,X,del(X)q27. They showed that the X chromosome with the deletion was inactivated in all cells. The mother's identical twin sister had a son with severe hemophilia B. The proband was also lacking the paternal factor VIII gene, indicating that the deletion had occurred in the paternal X chromosome and had included the factor VIII locus. However, both the maternal and the paternal factor IX loci were present. The interpretation applied by Nisen et al. (1986) was that inactivation of the deleted, paternally derived X chromosome in all cells had provided the opportunity for expression of the hemophilia B gene which the proband had inherited from her mother. </p><p>By sequencing the complete factor IX gene in 2 sisters with hemophilia B with different phenotypes and no family history of hemorrhagic diathesis, Costa et al. (2000) found a common 5-prime splice site mutation in intron 3 (300746.0107) and an additional missense mutation (I344T; 300746.0108) in 1 sister. The presence of dysfunctional antigen in the latter strongly suggested that these mutations were in trans. Neither mutation was found in leukocyte DNA from the asymptomatic parents, but the mother was a somatic mosaic for the shared splice site mutation. The somatic mosaicism in the mother for the splice site mutation was demonstrated by studies of buccal and uroepithelial cells. The missense mutation was presumed to have resulted from a de novo mutation in the father's gametes. The compound heterozygous proband was a 14-year-old girl with moderate hemophilia B, manifest by hematomas, hemarthrosis, and epistaxis. A sister suffered only from rare hematomas. </p><p>In a population-based survey in the Netherlands, Plug et al. (2006) found that female carriers of hemophilia A and B bled more frequently than noncarrier women, especially after medical procedures, such as tooth extraction or tonsillectomy. Reduced clotting factor levels correlated with a mild hemophilia phenotype. Variation in clotting levels was attributed to lyonization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Chronic synovitis occurs in about 10% of Indian patients with severe hemophilia. Ghosh et al. (2003) reported an association between the development of chronic synovitis in patients with hemophilia and the HLA-B27 allele (142830.0001). They studied 473 patients, 424 with hemophilia A and 49 with hemophilia B. Twenty-one (64%) of 33 patients with both disorders had HLA-B27, compared to 23 (5%) of 440 with severe hemophilia without synovitis (odds ratio of 31.6). There were 3 sib pairs with hemophilia in whom only 1 sib had synovitis; all the affected sibs had the HLA-B27 allele, whereas the unaffected sibs did not. Chronic synovitis presented as swelling of the joint with heat and redness and absence of response to treatment with factor concentrate. Ghosh et al. (2003) suggested that patients with HLA-B27 may not be able to easily downregulate inflammatory mediators after bleeding in the joints, leading to chronic synovitis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hemophilia B is classically transmitted as an X-linked recessive disorder. Cutler et al. (2004) described a family in which the usual pattern of X-linked inheritance of hemophilia B was complicated by mosaicism in the proband's maternal grandfather. The proband was a male infant with severe factor IX deficiency who was initially thought to be a sporadic case. Testing of other family members identified his mother as a carrier and his asymptomatic maternal grandfather as having very mild factor IX deficiency. The causative mutation was identified as a 2-bp deletion (AG within codons 134-135) in the F9 gene (300746.0110). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Acquired Inhibitor</em></strong></p><p>
|
|
The treatment for factor IX deficiency is replacement of the missing coagulation factor by transfusion of plasma from a healthy individual. However, a subset of patients develop IgG antibodies against normal factor IX, which complicates treatment. George et al. (1971) reported a family in which 3 of 4 members with Christmas disease developed an inhibitor to factor IX after transfusion. The inhibitor was an IgG antibody directed against the activated form of factor IX (IXa). There was no immunologically detectable factor IX-like material in the affected family members without an inhibitor. The findings were consistent with previous postulates that inhibitors to factor IX develop only in patients with Christmas disease who lack the factor IX antigen. The fourth member of the family, who had no factor IX antigen, was transfused several times, but failed to develop antibodies to factor IX. George et al. (1971) noted that inhibitors to factor IX develop infrequently compared to factor VIII, suggesting that there may be a predisposition to the development of an inhibitor. </p><p>Giannelli et al. (1983) noted that treatment of patients with factor IX deficiency with normal plasma resulted in the development of specific anti-F9 antibodies in about 1% of all cases and about 2.5% of severe cases. The authors postulated that this may be due to complete absence of 'self' factor IX in the plasma recipient, such that the immune system regards the infused normal factor IX as foreign. Indeed, 4 patients with factor IX deficiency and F9 antibodies were found to have gross deletions in the F9 gene, resulting in complete absence of the protein. </p><p>In a patient with severe F9 deficiency who had developed a high-titer antibody, Hassan et al. (1985) observed a deletion of about 33 kb at the F9 locus. </p><p>By Southern blot analysis of 9 patients, including 2 brothers, with hemophilia B and F9 antibodies, Matthews et al. (1987) found that 2 had a total deletion of the F9 gene. The brothers were shown to have a presumably identical complex rearrangement of the gene involving 2 separate deletions. Five other patients had a structurally intact F9 gene. Matthews et al. (1987) concluded that whereas large structural defects in the F9 gene can predispose the patients to the development of antibody, the phenomenon can also be associated with other defects of the gene. </p><p>Green et al. (1988) identified a partial deletion in the F9 gene in a boy and his uncle, both of whom had hemophilia B and inhibitors to factor IX. The mother of the boy was a carrier. The deletion, called 'London-1,' most likely arose by nonhomologous recombination. </p><p>Wadelius et al. (1988) found total deletion of the F9 gene in 3 affected males in 1 family who did not have antibodies against native factor IX. Two of the patients, who were cousins, had inherited the same maternal HLA haplotype, suggesting that immune gene(s) located at the MHC locus may be important for the development of antibodies against factor IX. </p><p>Ljung et al. (2001) found that 11 (23%) of 48 patients with severe hemophilia B developed inhibitors and all of them had deletions or nonsense mutations. Thus, 11 of 37 (30%) patients with severe hemophilia B as a result of deletion/nonsense mutations developed inhibitors compared with none of 11 patients with missense mutations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe F9 deficiency who developed an inhibitor, Peake et al. (1984) detected a deletion in the F9 gene using 4 genomic gene probes. Similar studies of 8 female relatives using this method identified 2 as carriers. Used a genomic probe containing a TaqI polymorphism in the F9 gene, Giannelli et al. (1984) successfully identified carriers of Christmas disease in 3 affected families. </p><p>In eukaryotic DNA, a high proportion of CpG dinucleotides are methylated at the cytosine residue to give 5-methylcytosine. The restriction enzyme HhaI will not cleave at methylated CpG sites, but PCR can overcome this limitation. Winship et al. (1989) used PCR to detect a polymorphic HhaI site located 8 kb 3-prime to the F9 gene and estimated that almost half of female subjects can be expected to be heterozygous at this site. Detection of this marker using PCR was predicted to increase the proportion of persons in whom the carrier state of hemophilia B could be diagnosed, compared to using the restriction enzyme alone, which could be influenced by methylation status. </p><p>Koeberl et al. (1990) compared RFLP-based carrier detection of an X-linked disease with a direct method involving genomic amplification with transcript sequencing (GAWTS). They pointed out that the RFLP approach 'suffers from multiple levels of uncertainty.' They found that 22 at-risk females were diagnosed by direct testing, whereas only 11 females could be diagnosed by standard RFLP analysis. </p><p>Giannelli et al. (1992) used hemophilia B as a model of a genetic disease with marked mutational heterogeneity to lay out an overall strategy for genetic counseling. They started with the construction of a national database which could be used for diagnosis and genetic counseling on the basis of DNA abnormality. In the U.K. there were just over 1,000 patients with hemophilia B and these were probably derived from 500 to 600 families. They characterized the mutation in a group of unrelated patients and in only 1 of 170 patients examined from the Swedish and British series did they fail to find a mutation in the essential regions of the gene. Thus the screening procedures used were capable of detecting all types of mutations. By phenotype/genotype correlations the authors generated information of prognostic value concerning each of those mutations. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
|
|
In 5 kindreds studied in detail, Poon et al. (1987) were able to determine the carrier status of hemophilia B in all 11 females at risk; prenatal diagnosis could be offered to the offspring of each of the 6 carriers identified. </p><p>Green et al. (1991) suggested a strategy for facilitating carrier and prenatal diagnosis by identification of all hemophilia B mutations in a given population so that only the relevant parts of the molecule need be focused on when performing amplification mismatch detection (AMD) as developed by Montandon et al. (1989). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Linkage studies in the early 1960s suggested that the hemophilia A and B loci were not allelic; hemophilia A was found to be tightly linked to colorblindness (CBD; 303800) on Xq28, whereas hemophilia B apparently was not linked to colorblindness. In the dog, Brinkhous et al. (1973) showed that the loci for hemophilias A and B were probably 50 map units or more apart. The genetic distance between the 2 loci was estimated to be about 50 map units in man as well. </p><p>By in situ hybridization, Purrello et al. (1985) showed that the loci for hemophilia A and hemophilia B flank the fragile X site (300624). The authors believed that this finding, combined with the knowledge that hemophilia B recombines freely with at least 2 loci of the G6PD (305900) cluster, supported the Siniscalco hypothesis that the chromosomal segment in which the fragile X site occurs is normally a region of high meiotic recombination (Szabo et al., 1984). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using genomic DNA probes, Chen et al. (1985) identified a partial intragenic deletion in the F9 gene in 7 affected members of a family with severe hemophilia B. </p><p>In affected members of a family with severe factor IX deficiency and no detectable factor IX protein, Taylor et al. (1988) identified a complete deletion of the F9 gene that extended at least 80 kb 3-prime of the gene. The proband did not have antibodies to factor IX, despite total deletion of the gene. </p><p>Matthews et al. (1988) discussed the family originally reported by Peake et al. (1984) as having an X-chromosome deletion of minimum size 114 kb that included the entire F9 gene. By isolation of further 3-prime flanking probes, they located the 3-prime breakpoint of the deletion to a position 145 kb 3-prime to the start of the F9 gene. Abnormal junction fragments detected at the breakpoint were used in the detection of carriers. </p><p>In a patient with severe hemophilia B, Siguret et al. (1988) found loss of the Taq1 restriction site at the 5-prime end of exon 8 of the F9 gene. Using oligonucleotide probes and PCR-amplified DNA for sequencing of the affected region, the authors identified a C-to-T change in the catalytic domain of the protein, resulting in premature termination. The change resulted from a CpG mutation. </p><p>By use of PCR followed by sequencing, Bottema et al. (1989) identified mutations in the F9 gene (see, e.g., 300746.0051) in all 14 hemophilia B patients studied. Analysis for heterozygosity in at-risk female relatives was then done, either by sequencing the appropriate region or by detection of an altered restriction site. </p><p>Green et al. (1991) provided a list of point mutations that cause hemophilia B. Sommer et al. (1992) estimated that missense mutations cause only 59% of moderate and severe hemophilia B and that these mutations are almost always (95%) of independent origin (i.e., de novo mutations). In contrast, missense mutations were found in virtually all (97%) families with mild disease and only a minority of these (41%) were of independent origin. </p><p>Giannelli et al. (1993) reported on the findings in a database of 806 patients with hemophilia B in whom the defect in factor IX had been identified at the molecular level. A total of 379 independent mutations were described. The list included 234 different amino acid substitutions. There were 13 promoter mutations, 18 mutations in donor splice sites, 15 mutations in acceptor splice sites, and 4 mutations creating cryptic splice sites. In analyses of DNA from 290 families with hemophilia B (203 independent mutations), Ketterling et al. (1994) found 12 deletions more than 20 bp long. Eleven of these were more than 2 kb long and one was 1.1 kb. </p><p>Giannelli et al. (1996) described the sixth edition of their hemophilia B database of point mutations and short (less than 30 bp) additions and deletions. The 1,380 patient entries were ordered by the nucleotide number of their mutation. References to published mutations were given and the laboratories generating the data were indicated. Giannelli et al. (1997) described the seventh edition of their database; 1,535 patient entries were ordered by the nucleotide number of their mutation. When known, details were given on factor IX activity, factor IX antigen in the circulation, presence of inhibitor, and origin of mutation. </p><p>Ljung et al. (2001) surveyed a series comprising all 77 known families with hemophilia B in Sweden. The disorder was severe in 38, moderate in 10, and mild in 29. A total of 51 different mutations were found. Ten of the mutations, all C-to-T or G-to-A transitions, recurred in 1 to 6 additional families. Using haplotype analysis of 7 polymorphisms in the F9 gene, Ljung et al. (2001) found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate hemophilia, 23 (48%) had a sporadic case compared with 31 families of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations; 11 of 23 of the mothers were proven carriers; and in the remaining 7 families, it was not possible to determine carriership. </p><p>Rogaev et al. (2009) identified a splice site mutation in the F9 gene (300746.0113) as the causative mutation for the 'Royal disease,' the form of hemophilia transmitted from Queen Victoria to European royal families and transmitted to her granddaughter, Russian Empress Alexandra and her son, Crown Prince Alexei. </p><p><strong><em>Mutation Rate</em></strong></p><p>
|
|
In an analysis of 1,485 families with hemophilia A or hemophilia B, Barrai et al. (1985) estimated the proportion of sporadic cases to be 0.166 and 0.078, respectively. The age of maternal grandfathers at birth of the mother of hemophilia B cases was higher than that of appropriate controls. </p><p>In the population of families with hemophilia B at the Malmo Haemophilia Centre, Montandon et al. (1992) estimated that the overall mutation rate was 4.1 x 10(-6) and that the ratio of male to female specific mutation rates was 11. Three of 13 isolated cases had a new mutation, whereas the other 10 had mothers who carried a new mutation. </p><p>Kling et al. (1992) found that 24 of 45 hemophilia B patients in Malmo, Sweden, had no affected family members. Three of 13 families with 1 patient available for study had a do novo mutation, whereas the defect was inherited from a carrier mother in the remaining 10. All 10 of these carrier mothers had de novo mutation, as their fathers were phenotypically normal and the grandmothers were noncarriers. In all 6 of the 10 cases in whom RFLP patterns were informative, the mutation was of paternal origin, and the average age of the father at the birth of the new carrier female was 41.5 years. These data supported a paternal age effect and a higher mutation rate in males than in females regarding factor IX mutations. </p><p>Among 43 families with hemophilia B, Ketterling et al. (1993) found that 25 had a mutation in the female germline and 18 in the male germline. The excess of germline origins in females did not imply an overall excess mutation rate per basepair, because when the mother and maternal grandparents were analyzed, the excess of X chromosomes in females, 4:1, skewed the data in favor of female origins. Bayesian analysis corrected for this bias and indicated that the 25:18 ratio actually represented a predominance of mutations in males. Transitions at the dinucleotide CpG, estimated to account for 36% of mutations in the F9 gene (Koeberl et al., 1990), showed the most striking male predominance of mutation, 11:1. This finding was comparable with previous data suggesting that methylation at CpG dinucleotides is reduced or absent in the female germline (Driscoll and Migeon, 1990). This effect, rather than an increased number of replications in the male germ cells, likely accounted for the male excess. </p><p>In studies of the patterns of independent mutation resulting in hemophilia B in 127 Caucasian and 44 non-Caucasian patients, Gostout et al. (1993) could find no differences, suggesting either predominance of endogenous processes or common mutagen exposure rather than mutagen exposure specifically associated with non-Caucasian status or non-Western life style. </p><p>Green et al. (1999) conducted a population-based study of hemophilia B mutations in the United Kingdom in order to construct a national confidential database of mutations and pedigrees to be used for the provision of carrier and prenatal diagnoses based on mutation detection. This allowed the direct estimate of overall mutation rate, male mutation rate, and female mutation rate for hemophilia B. The values obtained per gamete per generation and the 95% confidence intervals were 7.73 (6.29-9.12) x 10(-6) for overall mutation rate; 18.8 (14.5-22.9) x 10(-6) for male mutation rate; and 2.18 (1.44-3.16) x 10(-6) for female mutation rate. The ratio of male-to-female mutation rates was 8.64 (95% CI, 5.46-14.5). Attempts to detect evidence of gonadal mosaicism for hemophilia B mutation in suitable families did not detect any instances of ovarian mosaicism in 47 available opportunities. This suggested that the risk of a noncarrier mother manifesting as a gonadal mosaic by transmitting the mutation to a second child should be less than 0.062. </p><p>Giannelli et al. (1999) also estimated the rates per base per generation of specific types of mutations, using their direct estimate of the overall mutation rate for hemophilia B and information on the mutations present in the U.K. population as well as those reported year by year in the hemophilia B world database. These rates were as follows: transitions at CpG sites, 9.7 x 10(-8); other transitions, 7.3 x 10(-9); transversions at CpG sites, 5.4 x 10(-9); other transversions, 6.9 x 10(-9); and small deletions/insertions causing frameshifts, 3.2 x 10(-10). </p><p>Ketterling et al. (1999) estimated the male:female ratio of mutations in the F9 gene by Bayesian analysis of 59 families. The overall ratio was estimated at 3.75. It varied with the type of mutation, from 6.65 and 6.10 for transitions at CpG and A:T to G:C transitions at non-CpG dinucleotides, respectively, to 0.57 and 0.42 for microdeletions/microinsertions and large deletions (more than 1 kb), respectively. The value for the 2 subsets of non-CpG transitions differed (6.10 for A:T to G:C vs 0.80 for G:C to A:T). Somatic mosaicism was detected in 11% of the 45 'origin individuals' for whom the causative mutation was visualized directly by genomic sequencing of leukocyte DNA (estimated sensitivity of approximately 1 part in 20). Four of the 5 defined somatic mosaics had G:C to A:T transitions at non-CpG dinucleotides, hinting that this mutation subtype may occur commonly early in embryogenesis. The age at conception was analyzed for 41 U.S. Caucasian families in which the age of the origin parent and the year of conception for the first carrier/hemophiliac were available. No evidence for a paternal age effect was seen; however, an advanced maternal age effect was observed (P = 0.03) and was particularly prominent in transversions. This suggested that an increased maternal age results in a higher rate of transmitted mutations, whereas the increased number of mitotic replications associated with advanced paternal age has little, if any, effect on the rate of transmitted mutation. </p><p>Liu et al. (2000) found that the pattern of germline mutations in 66 hemophilia B patients from mainland China was similar to that in U.S. Caucasians, blacks, and Mexican Hispanics. The existence of a ubiquitous mutagen or the possibility that multiple mutagens could produce the same pattern of mutation was considered unlikely; the findings were compatible with the inference that endogenous processes predominate in germline mutations. </p><p>Ljung et al. (2001) found that the ratio of male to female mutation rates was 5:3 and that the overall mutation rate per gamete per generation was 5.4 x 10(-6). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Therapy</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Gerrard et al. (1993) introduced a recombinant human F9 cDNA into cultured primary human keratinocytes by means of a defective retroviral vector. In tissue culture, transduced keratinocytes were found to secrete biologically active factor IX. After transplantation of these cells into nude mice, human factor IX was detected in the bloodstream in small quantities for 1 week. </p><p>Kay et al. (2000) initiated a clinical study of intramuscular injection of an AAV vector expressing human factor IX in adults with severe hemophilia B. The study had a dose-escalation design. Assessment in the first 3 patients of safety and gene transfer and expression showed no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against factor IX. By PCR and Southern blot analyses of muscle biopsies, Kay et al. (2000) found that the vector sequences were present in muscle, and demonstrated expression of factor IX by immunohistochemistry. They observed modest changes in clinical endpoints, including circulating levels of factor IX and frequency of factor IX protein infusion. The evidence of gene expression at low doses of vector suggested that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offered the possibility of converting severe hemophilia B to a milder form of the disease. </p><p>Manno et al. (2003) investigated the safety of intramuscular injection of a recombinant AAV (rAAV) vector expressing factor IX in patients with hemophilia B. Muscle biopsies of injection sites performed 2 to 10 months after vector administration confirmed gene transfer as evidenced by Southern blot and transgene expression as evidenced by immunohistochemical staining. However, circulating levels of factor IX were less than 2% in all cases and less than 1% in most. Manno et al. (2003) concluded that the results demonstrated the safety of intramuscular rAAV administration in humans in a manner similar to that used in mice and hemophilic dogs (Herzog et al. (1997, 1999)). </p><p>Nathwani et al. (2011) infused a single dose of a serotype-8-pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX transgene in a peripheral vein in 6 patients with severe hemophilia B (factor IX activity less than 1% of normal values). Study participants were enrolled in 1 of 3 cohorts, with 2 participants in each group, and given a high, intermediate, or low dose of vector. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. AAV-mediated expression of factor IX at 2 to 11% of normal levels was observed in all participants. Four of the 6 discontinued prophylaxis and remained free of spontaneous hemorrhage; in the other 2, the interval between prophylactic injections was increased. Of the 2 participants who received the high dose of vector, 1 had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid-specific T cells in peripheral blood; the other had a slight increase in liver enzyme levels, the cause of which was less clear. Each of these 2 participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained factor IX levels in the range of 3 to 11% of normal values. </p><p>George et al. (2017) infused a single-stranded AAV vector (known as SPK-9001) consisting of a bioengineered capsid, liver-specific promoter, and factor IX Padua (factor IX-R338L, 300746.0112) transgene at a dose of 5 x 10(11) vector genomes per kg of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. The naturally occurring gain-of-function factor IX-R338L results in specific activity that is 8 to 12 times as high as nonmutant factor IX. No serious adverse events occurred during or after vector infusion. Vector-derived factor IX coagulant activity was sustained in all the participants, with a mean (+/- SD) steady-state factor IX coagulant activity of 33.7 +/- 18.5% (range, 14-81). On cumulative follow-up of 492 weeks among all the participants (range in individual participants, 28-78 weeks), the annualized bleeding rate was significantly reduced (mean rate, 11.1 events per year (range, 0-48) before vector administration versus 0.4 events per year (range, 0-4) after administration; p = 0.02), as was factor use (mean dose, 2908 IU per kg (range, 0-8090) before vector administration versus 49.3 IU per kg (range, 0-376) after administration; p = 0.004). After vector administration, 8 of 10 participants did not use factor, and 9 of 10 did not have bleeds. An asymptomatic increase in liver enzyme levels developed in 2 participants and resolved with short-term prednisone treatment. George et al. (2017) concluded that the transgene factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use. </p><p>Pipe et al. (2023) reported the results of an open-label, phase 3 study, after a 6-month lead-in of factor IX prophylaxis, of a 1-time infusion of AAV5 vector expressing the Padua factor IX variant (etranacogene dezaparvovec, 2 x 10(13) genomic copies per kg body weight) to 54 men aged 19 to 75 years (mean age 41.5 years) with hemophilia B with factor IX activity less than 2% of normal, regardless of preexisting AAV5 neutralizing antibodies. The annualized bleeding rate decreased from 4.19 (95% CI, 3.22-5.45) during the lead-in period to 1.51 (95% CI, 0.81-2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36, demonstrating superiority of the gene therapy compared with the factor IX prophylaxis. Factor IX activity had increased from baseline by a mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment. Usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant (p less than 0.001 for all comparisons). Benefits and safety were observed in participants with pretreatment AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. </p><p>Cuker et al. (2024) reported results of a phase 3 open-label study of fidanacogene elaparvovec, an AAV vector designed to deliver transgene production of factor IX Padua (FIX-R338L) for hemophilia B. Forty-five men aged 18 to 62 years (mean 33.2 years) with factor IX levels of 2% or less who had received at least 6 months of therapy with prophylactic factor IX concentrate were infused with a single dose of fidanacogene elaparvovec. Of the 45 participants, 44 completed at least 15 months of follow-up. The primary end point, tested for noninferiority, was the annualized bleeding rate (treated and untreated bleeding episodes) from week 12 to month 15 after treatment with fidanacogene elaparvovec as compared with the prophylaxis lead-in period. The annualized rate of bleeding for all bleeding episodes decreased by 71%, from 4.42 (95% confidence interval (CI), 1.80 to 7.05) at baseline to 1.28 (95% CI, 0.57 to 1.98) after gene therapy, a treatment difference of -3.15 episodes (95% CI, -5.46 to -0.83; p = 0.008). The authors concluded that this result showed the noninferiority and superiority of fidanacogene elaparvovec to prophylaxis. At 15 months, the mean factor IX activity was 26.9% (median, 22.9%; range, 1.9 to 119.0) by 1-stage SynthASil assay. A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels (or both) starting between 11 and 123 days. No infusion-related serious adverse events, thrombotic events, development of factor IX inhibitors, or malignant conditions were observed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Giannelli et al. (1983) stated that 798 cases of Christmas disease were known in the U.K., corresponding to a frequency of 1 in 30,000 males. </p><p>Connor et al. (1985), by total ascertainment, found 28 families with hemophilia B in the west of Scotland (prevalence = 1/26,870 males). Of 26 living obligate carriers, 42% were heterozygous for a TaqI polymorphism recognized by the factor IX genomic probe. Linkage disequilibrium was apparent for this RFLP and hemophilia B in the west of Scotland. This surprising finding suggested that some of these families might be related. </p><p>Soucie et al. (1998) studied the frequency of hemophilia A and hemophilia B in 6 U.S. states: Colorado, Georgia, Louisiana, Massachusetts, New York, and Oklahoma. The age-adjusted prevalence of hemophilia in all 6 states in 1994 was 13.4 cases per 100,000 males (10.5 hemophilia A and 2.9 hemophilia B). The prevalence by race/ethnicity was 13.2 cases per 100,000 white, 11.0% among African American, and 11.5% among Hispanic males. Application of age-specific prevalence rates from the 6 surveillance states to the U.S. population resulted in an estimated national population of 13,320 cases of hemophilia A and 3,640 cases of hemophilia B. For the 10-year period 1982 to 1991, the average incidence of hemophilia A and B in the 6 surveillance states was estimated to be 1 in 5,032 live male births. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kundu et al. (1998) generated a transgenic mouse model of hemophilia B by targeted disruption of the murine f9 gene. The tail bleeding time of hemizygous male mice was markedly prolonged compared with those of normal and carrier female litter mates. Seven of 19 affected male mice died of exsanguination after tail snipping, and 2 affected mice died of umbilical cord bleeding. Ten affected mice survived to 4 months of age. Aside from the factor IX defect, carrier female and hemizygous male mice had no liver pathology by histologic examination, were fertile, and transmitted the mutation in the expected mendelian frequency. </p><p>Gu et al. (1999) found factor IX deficiency in 2 distinct dog breeds. In 1 breed, the disorder was associated with a large deletion mutation, spanning the entire 5-prime region of the F9 gene extending to exon 6. In the second breed, an insertion of approximately 5 kb disrupted exon 8. The insertion was associated with alternative splicing between a donor site 5-prime and acceptor site 3-prime to the normal exon 8 splice junction, with introduction of a new stop codon. </p><p>Brooks et al. (2003) found that mild hemophilia B in a large pedigree of German wirehaired pointers was caused by a line-1 insertion in the factor IX gene. The insert could be traced through at least 5 generations and segregated with the hemophilia B phenotype. </p><p>In transgenic mice with the hemophilia B Leyden phenotype (-20T-A; 300746.0001), which usually show amelioration of the disorder after puberty, Kurachi et al. (2009) found that expression of different F9 minigenes with or without the age-related stability element (ASE) in the 5-prime untranslated region resulted in different disease course. Mice lacking the ASE failed to show the Leyden phenotype with only transient F9 expression at puberty, whereas mice with ASE showed normal and sustained pubertal F9 recovery. These changes were not sex-dependent, indicating that testosterone and androgen are not responsible. Further studies showed that the transcription factor Ets1 (164720) was the specific ASE-binding protein, and F9 expression was abolished by hypophysectomy, but restored with growth hormone (GH; 139250) administration in both males and females. These results provided a molecular mechanism for the puberty-related Leyden phenotype. Kurachi et al. (2009) also generated transgenic mice expressing the Brandenberg F9 mutation (-26G-C; 300746.0097), which showed a severe phenotype without amelioration after puberty. </p><p><strong><em>Animal Studies of Gene Therapy</em></strong></p><p>
|
|
Busby et al. (1985) transfected baby hamster kidney (BHK) cells with a plasmid containing a gene for human factor IX and a plasmid containing a selectable marker. The cells secreted material that these authors believed to be authentic factor IX. Armentano et al. (1990) used a recombinant retroviral factor to transfer the human factor IX gene into hepatocytes from 3-week old New Zealand white rabbits. The infected cells produced human factor IX that was indistinguishable from the enzyme derived from normal human plasma. </p><p>Choo et al. (1987) introduced a full-length human factor IX cDNA containing all the natural mRNA sequences plus some flanking intron sequences combined with a metallothionein promoter. This DNA clone was microinjected into the pronuclei of fertilized murine eggs. The transgenic mice expressed high levels of mRNA, gamma-carboxylated and glycosylated protein, and biologic clotting activity that were indistinguishable from normal human plasma factor IX. </p><p>Armentano et al. (1990) used a recombinant retroviral factor to transfer the factor IX gene into hepatocytes from 3-week old New Zealand white rabbits. The infected cells produced human factor IX that was indistinguishable from the enzyme derived from normal human plasma. </p><p>Axelrod et al. (1990) demonstrated that primary skin fibroblasts from hemophilic dogs, transduced by recombinant retrovirus containing a canine factor IX cDNA, secreted high levels of biologically active canine factor IX into the medium. </p><p>Yao et al. (1991) infected rat capillary endothelial cells (CECs) with a Moloney murine leukemia virus-derived retrovirus vector that contained human factor IX cDNA. They found that a single RNA transcript of 4.4 kb, predicted by the construct, and a recombinant factor IX of 68 kD identical to purified plasma factor IX were formed. The recombinant factor IX that was produced showed full clotting activity, demonstrating that CECs have an efficient mechanism for posttranslational modifications, including gamma-carboxylation, essential for its biologic activity. These results, in addition to other properties of the endothelium, suggested that CECs could serve as an efficient drug delivery vehicle producing factor IX for somatic gene therapy of hemophilia B. </p><p>Kay et al. (1993) developed a method for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, and showed that the method resulted in the persistent expression of exogenous genes. When canine factor IX cDNA was transduced directly into hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reduction of whole blood clotting time and partial thromboplastin time of the treated animals. </p><p>Wang et al. (1997) generated a mouse model in which the gene encoding factor IX was disrupted by homologous recombination. The nullizygous mice were devoid of factor IX antigen in plasma. Consistent with the bleeding disorder, the factor IX coagulant activities for wildtype, heterozygous, and homozygous mice were 92, 53, and less than 5%, respectively, in activated partial thromboplastin time assays. Plasma factor IX activity in the deficient -/- mice was restored by introducing wildtype murine factor IX gene via adenoviral vectors. Thus, these factor IX-deficient mice provided a useful animal model for gene therapy studies of hemophilia B. The factor IX-deficient mice showed extensive bleeding after clipping a portion of the tail and bled to death unless the wound was cauterized. Additionally, in contrast to the normal mice, they showed swollen extremities and extensive hemorrhagic lesions after trauma. Female homozygous -/- mice gave birth without complications. </p><p>Schnieke et al. (1997) produced transgenic sheep carrying the human factor IX gene by nuclear transfer. Ovine primary fetal fibroblasts were cotransfected with a neomycin-resistance marker gene (neo) and a human coagulation factor IX genomic construct designed for expression of the encoded protein in sheep milk. Nuclear transfer to enucleated oocytes was performed using either cloned transfectant fibroblasts or a population of neomycin-resistant cells as donors. Six transgenic lambs were liveborn: 3 produced from cloned transfectant cells contained factor IX and neo transgenes, whereas 3 produced from the uncloned population contained the marker gene only. </p><p>Preclinical studies in mice and hemophilic dogs showed that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX into skeletal muscle results in sustained expression of factor IX at levels sufficient to correct the hemophilic phenotype (Herzog et al., 1997; Herzog et al., 1999). </p><p>Yant et al. (2000) described the successful use of transposon technology for the nonhomologous insertion of foreign genes into the genomes of adult mammals using naked DNA. Yant et al. (2000) showed that the 'Sleeping Beauty' transposase, the product of a synthetic transposable element, can efficiently insert transposon DNA into the mouse genome in approximately 5 to 6% of transfected mouse liver cells. Chromosomal transposition resulted in long-term expression (greater than 5 months) of human blood coagulation factor IX at levels that were therapeutic in a mouse model of hemophilia B. </p><p>Li et al. (2011) showed that zinc finger nucleases are able to induce double-strand breaks efficiently when delivered directly to mouse liver and that, when codelivered with an appropriately designed gene targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the zinc finger nuclease-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of hemophilia B, and remained persistent after induced liver regeneration. Thus, Li et al. (2011) concluded that zinc finger nuclease-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Bernardi et al. (1985); Blackburn et al. (1962); Brown et al. (1970);
|
|
Brownlee (1988); Chan et al. (1998); Connor et al. (1986); Crossley
|
|
et al. (1990); Crossley et al. (1989); Didisheim and Vandervoort
|
|
(1962); Giannelli et al. (1992); Girolami et al. (1980); Goldsmith et
|
|
al. (1979); Green et al. (1989); Green et al. (1993); Green et al.
|
|
(1991); Grunebaum et al. (1984); Hay et al. (1986); Hirosawa et al.
|
|
(1990); Holmberg et al. (1980); Kasper et al. (1977); Ketterling et
|
|
al. (1991); Kitchens et al. (1976); Koeberl et al. (1990); Lillicrap
|
|
et al. (1986); Montandon et al. (1990); Neal et al. (1973); Neuschatz
|
|
and Necheles (1973); Orstavik et al. (1985); Orstavik et al. (1979);
|
|
Peake et al. (1989); Poort et al. (1989); Tanimoto et al. (1988);
|
|
Taylor et al. (1991); Vidaud et al. (1993); Wall et al. (1967);
|
|
Whittaker et al. (1962)
|
|
</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">
|
|
Aggeler, P. M., White, S. G., Glendening, M. B., Page, E. W., Leake, T. B., Bates, G.
|
|
<strong>Plasma thromboplastin component (PTC) deficiency: a new disease resembling hemophilia.</strong>
|
|
Proc. Soc. Exp. Biol. Med. 79: 692-694, 1952.
|
|
|
|
|
|
[PubMed: 14920537]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3181/00379727-79-19488]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Armentano, D., Thompson, A. R., Darlington, G., Woo, S. L. C.
|
|
<strong>Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: potential for gene therapy of hemophilia B.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 6141-6145, 1990.
|
|
|
|
|
|
[PubMed: 2385589]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.16.6141]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Axelrod, J. H., Read, M. S., Brinkhous, K. M., Verma, I. M.
|
|
<strong>Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 5173-5177, 1990.
|
|
|
|
|
|
[PubMed: 2367529]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.13.5173]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barrai, I., Cann, H. M., Cavalli-Sforza, L. L., Barbujani, G., De Nicola, P.
|
|
<strong>Segregation analysis of hemophilia A and B.</strong>
|
|
Am. J. Hum. Genet. 37: 680-699, 1985.
|
|
|
|
|
|
[PubMed: 9556658]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernardi, F., Del Senno, L., Barbieri, R., Buzzoni, D., Gambari, R., Marchetti, G., Conconi, F., Panicucci, F., Positano, M., Pitruzzello, S.
|
|
<strong>Gene deletion in an Italian haemophilia B subject.</strong>
|
|
J. Med. Genet. 22: 305-307, 1985.
|
|
|
|
|
|
[PubMed: 4045960]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.22.4.305]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Briet, E., Veltkamp, J. J.
|
|
<strong>Variants of vitamin K dependent coagulation factors. (Editorial)</strong>
|
|
Acta Haemat. 62: 1-3, 1979.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Veltkamp, J. J.
|
|
<strong>The abnormal factor IX of hemophilia B+ variants.</strong>
|
|
Thromb. Haemost. 40: 335-349, 1978.
|
|
|
|
|
|
[PubMed: 734633]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R.
|
|
<strong>Christmas disease: a condition previously mistaken for haemophilia.</strong>
|
|
Brit. Med. J. 2: 1378-1382, 1952.
|
|
|
|
|
|
[PubMed: 12997790]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.2.4799.1378]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blackburn, E. K., Monaghan, J. H., Lederer, H., MacFie, J. M.
|
|
<strong>Christmas disease associated with primary capillary abnormalities.</strong>
|
|
Brit. Med. J. 1: 154-156, 1962.
|
|
|
|
|
|
[PubMed: 13869677]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.1.5272.154]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Sommer, S. S.
|
|
<strong>Direct carrier testing in 14 families with haemophilia B.</strong>
|
|
Lancet 334: 526-529, 1989. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: 2570235]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)90653-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Briet, E., Bertina, R. M., van Tilburg, N. H., Veltkamp, J. J.
|
|
<strong>Hemophilia B Leyden: a sex-linked hereditary disorder that improves after puberty.</strong>
|
|
New Eng. J. Med. 306: 788-790, 1982.
|
|
|
|
|
|
[PubMed: 7062952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198204013061306]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brinkhous, K. M., Davis, P. D., Graham, J. B., Dodds, W. J.
|
|
<strong>Expression and linkage of genes for X-linked hemophilias A and B in the dog.</strong>
|
|
Blood 41: 577-585, 1973.
|
|
|
|
|
|
[PubMed: 4688873]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brooks, M. B., Gu, W., Barnas, J. L., Ray, J., Ray, K.
|
|
<strong>A line 1 insertion in the factor IX gene segregates with mild hemophilia B in dogs.</strong>
|
|
Mammalian Genome 14: 788-795, 2003.
|
|
|
|
|
|
[PubMed: 14722728]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00335-003-2290-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, P. E., Hougie, C., Roberts, H. R.
|
|
<strong>The genetic heterogeneity of hemophilia B.</strong>
|
|
New Eng. J. Med. 283: 61-64, 1970.
|
|
|
|
|
|
[PubMed: 5420360]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197007092830203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brownlee, G. G.
|
|
<strong>Haemophilia B: a review of patient defects, diagnosis with gene probes and prospects for gene therapy.</strong>
|
|
Recent Adv. Haemat. 5: 251-265, 1988.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Busby, S., Kumar, A., Joseph, M., Halfpap, L., Insley, M., Berkner, K., Kurachi, K., Woodbury, R.
|
|
<strong>Expression of active human factor IX in transfected cells.</strong>
|
|
Nature 316: 271-273, 1985.
|
|
|
|
|
|
[PubMed: 3894976]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/316271a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, V. W. Y., Yip, B., Chim, C. S., Chan, T. K.
|
|
<strong>Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.</strong>
|
|
Am. J. Hemat. 58: 72-76, 1998.
|
|
|
|
|
|
[PubMed: 9590153]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8652(199805)58:1<72::aid-ajh13>3.0.co;2-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Yoshitake, S., Chance, P. F., Bray, G. L., Thompson, A. R., Scott, C. R., Kurachi, K.
|
|
<strong>An intragenic deletion of the factor IX gene in a family with hemophilia B.</strong>
|
|
J. Clin. Invest. 76: 2161-2164, 1985.
|
|
|
|
|
|
[PubMed: 3001143]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112222]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Choo, K. H., Raphael, K., McAdam, W., Peterson, M. G.
|
|
<strong>Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.</strong>
|
|
Nucleic Acids Res. 15: 871-884, 1987.
|
|
|
|
|
|
[PubMed: 3029708]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/15.3.871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Connor, J. M., Pettigrew, A. F., Hann, I. M., Forbes, C. D., Lowe, G. D. O., Affara, N. A.
|
|
<strong>Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland.</strong>
|
|
J. Med. Genet. 22: 441-446, 1985.
|
|
|
|
|
|
[PubMed: 4078877]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.22.6.441]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Connor, J. M., Pettigrew, A. F., Shiach, C., Hann, I. M., Lowe, G. D. O., Forbes, C. D.
|
|
<strong>Application of three intragenic DNA polymorphisms for carrier detection in haemophilia B.</strong>
|
|
J. Med. Genet. 23: 300-309, 1986.
|
|
|
|
|
|
[PubMed: 3018248]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.23.4.300]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M.
|
|
<strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong>
|
|
Blood 96: 1585-1587, 2000.
|
|
|
|
|
|
[PubMed: 10942410]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crossley, M., Winship, P. R., Austen, D. E. G., Rizza, C. R., Brownlee, G. G.
|
|
<strong>A less severe form of haemophilia B Leyden.</strong>
|
|
Nucleic Acids Res. 18: 4633, 1990.
|
|
|
|
|
|
[PubMed: 2388855]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/18.15.4633]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crossley, P. M., Winship, P. R., Black, A., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Unusual case of haemophilia B. (Letter)</strong>
|
|
Lancet 333: 960 only, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 2565449]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)92540-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cuker, A., Kavakli, K., Frenzel, L., Wang, J.-D., Astermark, J., Cerqueira, M. H., Iorio, A., Katsarou-Fasouli, O., Klamroth, R., Shapiro, A. D., Hermans, C., Ishiguro, A., and 12 others.
|
|
<strong>Gene therapy with fidanacogene elaparvovec in adults with hemophilia B.</strong>
|
|
New Eng. J. Med. 391: 1108-1118, 2024.
|
|
|
|
|
|
[PubMed: 39321362]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa2302982]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F.
|
|
<strong>Germline mosaicism resulting in the transmission of severe hemophilia B from a grandfather with a mild deficiency.</strong>
|
|
Am. J. Med. Genet. 129A: 13-15, 2004.
|
|
|
|
|
|
[PubMed: 15266608]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30162]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Denson, K. W., Biggs, P., Mannucci, P. M.
|
|
<strong>An investigation of three patients with Christmas disease due to an abnormal type of factor IX.</strong>
|
|
J. Clin. Path. 21: 160-165, 1968.
|
|
|
|
|
|
[PubMed: 4972271]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jcp.21.2.160]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Didisheim, P., Vandervoort, R. L. E.
|
|
<strong>Detection of carriers for factor IX (PTC) deficiency.</strong>
|
|
Blood 20: 150-155, 1962.
|
|
|
|
|
|
[PubMed: 13886232]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Driscoll, D. J., Migeon, B. R.
|
|
<strong>Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations.</strong>
|
|
Somat. Cell Molec. Genet. 16: 267-282, 1990.
|
|
|
|
|
|
[PubMed: 1694309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01233363]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
George, J. N., Miller, G. M., Breckenridge, R. T.
|
|
<strong>Studies on Christmas disease: investigation and treatment of a familial acquired inhibitor of factor IX.</strong>
|
|
Brit. J. Haemat. 21: 333-342, 1971.
|
|
|
|
|
|
[PubMed: 4998792]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1971.tb03445.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
George, L. A., Sullivan, S. K., Giermasz, A., Rasko, J. E. J., Samelson-Jones, B. J., Ducore, J., Cuker, A., Sullivan, L. M., Majumdar, S., Teitel, J., McGuinn, C. E., Ragni, M. V., and 16 others.
|
|
<strong>Hemophilia B gene therapy with a high-specific-activity factor IX variant.</strong>
|
|
New Eng. J. Med. 377: 2215-2227, 2017.
|
|
|
|
|
|
[PubMed: 29211678]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1708538]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gerrard, A. J., Hudson, D. L., Brownlee, G. G., Watt, F. M.
|
|
<strong>Towards gene therapy for haemophilia B using primary human keratinocytes.</strong>
|
|
Nature Genet. 3: 180-183, 1993.
|
|
|
|
|
|
[PubMed: 8499952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0293-180]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ghosh, K., Shankarkumar, U., Shetty, S., Mohanty, D.
|
|
<strong>Chronic synovitis and HLA B27 in patients with severe haemophilia.</strong>
|
|
Lancet 361: 933-934, 2003.
|
|
|
|
|
|
[PubMed: 12648975]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(03)12763-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giangrande, P. L. F.
|
|
<strong>Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors.</strong>
|
|
Brit. J. Haemat. 121: 703-712, 2003.
|
|
|
|
|
|
[PubMed: 12780784]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2003.04333.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Anagnostopoulos, T., Green, P. M.
|
|
<strong>Mutation rates in humans. II. Sporadic mutation-specific rates and rate of detrimental human mutations inferred from hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1580-1587, 1999.
|
|
|
|
|
|
[PubMed: 10577911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302652]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Anson, D. S., Choo, K. H., Rees, D. J. G., Winship, P. R., Ferrari, N., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency).</strong>
|
|
Lancet 323: 239-241, 1984. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 6142992]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(84)90122-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong>
|
|
Nature 303: 181-182, 1983.
|
|
|
|
|
|
[PubMed: 6843667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/303181a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Lillicrap, D. P., Ludwig, M., Olek, K., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--third edition, 1992.</strong>
|
|
Nucleic Acids Res. 20: 2027-2063, 1992.
|
|
|
|
|
|
[PubMed: 1598234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/20.suppl.2027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993.</strong>
|
|
Nucleic Acids Res. 21: 3075-3087, 1993.
|
|
|
|
|
|
[PubMed: 8392713]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/21.13.3075]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.</strong>
|
|
Nucleic Acids Res. 24: 103-118, 1996.
|
|
|
|
|
|
[PubMed: 8594556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/24.1.103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Figueiredo, M. S., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions, 7th edition.</strong>
|
|
Nucleic Acids Res. 25: 133-135, 1997.
|
|
|
|
|
|
[PubMed: 9016521]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/25.1.133]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Saad, S., Montandon, A. J., Bentley, D. R., Green, P. M.
|
|
<strong>A new strategy for the genetic counselling of diseases of marked mutational heterogeneity: haemophilia B as a model.</strong>
|
|
J. Med. Genet. 29: 602-607, 1992.
|
|
|
|
|
|
[PubMed: 1404290]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.29.9.602]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Girolami, A., Dal Bo Zanon, R., De Marco, L., Cappellato, G.
|
|
<strong>Hemophilia B with associated factor VII deficiency: a distinct variant of hemophilia B with low factor VII activity and normal factor VII antigen.</strong>
|
|
Blut 40: 267-273, 1980.
|
|
|
|
|
|
[PubMed: 7370439]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01080186]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goldsmith, J. C., Roer, M. E. S., Orringer, E. P.
|
|
<strong>A new treatment strategy for hemophilia B: incorporation of factor IX into red cell ghosts.</strong>
|
|
Am. J. Hemat. 7: 119-125, 1979.
|
|
|
|
|
|
[PubMed: 539589]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830070204]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gostout, B., Vielhaber, E., Ketterling, R. P., Yoon, H.-S., Bottema, C. D. K., Kasper, C. K., Koerper, M. A., Sommer, S. S.
|
|
<strong>Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians.</strong>
|
|
Hum. Molec. Genet. 2: 293-298, 1993.
|
|
|
|
|
|
[PubMed: 8499919]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.3.293]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Bentley, D. R., Mibashan, R. S., Giannelli, F.
|
|
<strong>Partial deletion by illegitimate recombination of the factor IX gene in a haemophilia B family with two inhibitor patients.</strong>
|
|
Molec. Biol. Med. 5: 95-106, 1988.
|
|
|
|
|
|
[PubMed: 3398774]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F.
|
|
<strong>Molecular pathology of haemophilia B.</strong>
|
|
EMBO J. 8: 1067-1072, 1989.
|
|
|
|
|
|
[PubMed: 2743975]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1989.tb03474.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Mitchell, V. E., McGraw, A., Goldman, E., Giannelli, F.
|
|
<strong>Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.</strong>
|
|
Hum. Mutat. 2: 103-107, 1993.
|
|
|
|
|
|
[PubMed: 8318985]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380020207]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Montandon, A. J., Bentley, D. R., Giannelli, F.
|
|
<strong>Genetics and molecular biology of haemophilias A and B.</strong>
|
|
Blood Coagul. Fibrinolysis 2: 539-565, 1991.
|
|
|
|
|
|
[PubMed: 1768766]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00001721-199108000-00007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Montandon, A. J., Ljung, R., Bentley, D. R., Nilsson, I.-M., Kling, S., Giannelli, F.
|
|
<strong>Haemophilia B mutations in a complete Swedish population sample: a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity.</strong>
|
|
Brit. J. Haemat. 78: 390-397, 1991.
|
|
|
|
|
|
[PubMed: 1873221]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb04453.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Saad, S., Lewis, C. M., Giannelli, F.
|
|
<strong>Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1572-1579, 1999.
|
|
|
|
|
|
[PubMed: 10577910]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302651]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grunebaum, L., Cazenave, J.-P., Camerino, G., Kloepfer, C., Mandel, J. L., Tolstoshev, P., Jaye, M., de la Salle, H., Lecocq, J. P.
|
|
<strong>Carrier detection of haemophilia B by using a restriction site polymorphism associated with the coagulation factor IX gene.</strong>
|
|
J. Clin. Invest. 73: 1491-1495, 1984.
|
|
|
|
|
|
[PubMed: 6325506]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI111354]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K.
|
|
<strong>Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.</strong>
|
|
Thromb. Haemost. 82: 1270-1275, 1999.
|
|
|
|
|
|
[PubMed: 10544912]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hashmi, K. Z., MacIver, J. E., Delamore, I. W.
|
|
<strong>Christmas disease in a female.</strong>
|
|
Lancet 312: 965-966, 1978. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: 81989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(78)92528-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hassan, H. J., Leonardi, A., Guerriero, R., Chelucci, C., Cianetti, L., Ciavarella, N., Ranieri, P., Pilolli, D., Peschle, C.
|
|
<strong>Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.</strong>
|
|
Blood 66: 728-730, 1985.
|
|
|
|
|
|
[PubMed: 2992643]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hay, C. W., Robertson, K. A., Yong, S.-L., Thompson, A. R., Growe, G. H., MacGillivray, R. T. A.
|
|
<strong>Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status.</strong>
|
|
Blood 67: 1508-1511, 1986.
|
|
|
|
|
|
[PubMed: 3008893]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Herzog, R. W., Hagstrom, J. N., Kung, S.-H., Tai, S. J., Wilson, J. M., Fisher, K. J., High, K. A.
|
|
<strong>Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 5804-5809, 1997.
|
|
|
|
|
|
[PubMed: 9159155]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.11.5804]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Herzog, R. W., Yang, E. Y., Couto, L. B., Hagstrom, J. N., Elwell, D., Fields, P. A., Burton, M., Bellinger, D. A., Read, M. S., Brinkhous, K. M., Podsakoff, G. M., Nichols, T. C., Kurtzman, G. J., High, K. A.
|
|
<strong>Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.</strong>
|
|
Nature Med. 5: 56-63, 1999.
|
|
|
|
|
|
[PubMed: 9883840]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/4743]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirosawa, S., Fahner, J. B., Salier, J.-P., Wu, C.-T., Lovrien, E. W., Kurachi, K.
|
|
<strong>Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 4421-4425, 1990.
|
|
|
|
|
|
[PubMed: 2352926]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.12.4421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Gustavii, B., Cordesius, E., Kristoffersson, A.-C., Ljung, R., Lofberg, L., Stromberg, P., Nilsson, I. M.
|
|
<strong>Prenatal diagnosis of hemophilia B by an immunoradiometric assay of factor IX.</strong>
|
|
Blood 56: 397-401, 1980.
|
|
|
|
|
|
[PubMed: 7407407]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hougie, C., Twomey, J. J.
|
|
<strong>Hemophilia B(M): a new type of factor-IX deficiency.</strong>
|
|
Lancet 289: 698-700, 1967. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 4163943]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(67)92179-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kasper, C. K., Osterud, B., Minami, J. Y., Schonick, W., Rapaport, S. I.
|
|
<strong>Hemophilia B--characterization of genetic variants and detection of carriers.</strong>
|
|
Blood 50: 351-366, 1977.
|
|
|
|
|
|
[PubMed: 884315]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B., Chew, A. J., Tai, S. J., Herzog, R. W., Arruda, V., Johnson, F., Scallan, C., Skarsgard, E., Flake, A. W., High, K. A.
|
|
<strong>Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.</strong>
|
|
Nature Genet. 24: 257-261, 2000.
|
|
|
|
|
|
[PubMed: 10700178]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/73464]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kay, M. A., Rothenberg, S., Landen, C. N., Bellinger, D. A., Leland, F., Toman, C., Finegold, M., Thompson, A. R., Read, M. S., Brinkhous, K. M., Woo, S. L. C.
|
|
<strong>In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs.</strong>
|
|
Science 262: 117-119, 1993.
|
|
|
|
|
|
[PubMed: 8211118]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.8211118]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S.
|
|
<strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong>
|
|
Hum. Genet. 87: 333-337, 1991.
|
|
|
|
|
|
[PubMed: 1864609]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00200915]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Bottema, C. D. K., Schaid, D. J., Cohen, M. P., Sexauer, C. L., Sommer, S. S.
|
|
<strong>Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.</strong>
|
|
Am. J. Hum. Genet. 52: 152-166, 1993.
|
|
|
|
|
|
[PubMed: 8434583]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E. L., Lind, T. J., Thorland, E. C., Sommer, S. S.
|
|
<strong>The rates and patterns of deletions in the human factor IX gene.</strong>
|
|
Am. J. Hum. Genet. 54: 201-213, 1994.
|
|
|
|
|
|
[PubMed: 8304338]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Li, X., Drost, J., Schaid, D. J., Kasper, C. K., Phillips, J. A., III, Koerper, M. A., Kim, H., Sexauer, C., Gruppo, R., Ambriz, R., Paredes, R., Sommer, S. S.
|
|
<strong>Germline origins in the human F9 gene: frequent G:C-to-A:T mosaicism and increased mutations with advanced maternal age.</strong>
|
|
Hum. Genet. 105: 629-640, 1999.
|
|
|
|
|
|
[PubMed: 10647899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004399900158]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kitchens, C. S., Levin, J., Smith, W. K.
|
|
<strong>Hemorrhagic diathesis in a carrier of hemophilia B.</strong>
|
|
Am. J. Med. 60: 138-143, 1976.
|
|
|
|
|
|
[PubMed: 1082713]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(76)90542-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kling, S., Ljung, R., Sjorin, E., Montandon, J., Green, P., Giannelli, F., Nilsson, I. M.
|
|
<strong>Origin of mutation in sporadic cases of haemophilia-B.</strong>
|
|
Europ. J. Haemat. 48: 142-145, 1992.
|
|
|
|
|
|
[PubMed: 1348478]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0609.1992.tb00585.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S.
|
|
<strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong>
|
|
Am. J. Hum. Genet. 47: 202-217, 1990.
|
|
|
|
|
|
[PubMed: 2198809]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sarkar, G., Ketterling, R. P., Chen, S.-H., Sommer, S. S.
|
|
<strong>Recurrent nonsense mutations at arginine residues cause severe hemophilia B in unrelated hemophiliacs.</strong>
|
|
Hum. Genet. 84: 387-390, 1990.
|
|
|
|
|
|
[PubMed: 1969838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00195805]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sommer, S. S.
|
|
<strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong>
|
|
Am. J. Med. Genet. 35: 600-608, 1990.
|
|
|
|
|
|
[PubMed: 1970704]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320350435]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Krepischi-Santos, A. C. V., Carneiro, J. D. A., Svartman, M., Bendit, I., Odone-Filho, V., Vianna-Morgante, A. M.
|
|
<strong>Deletion of the factor IX gene as a result of translocation t(X;1) in a girl affected by haemophilia B.</strong>
|
|
Brit. J. Haemat. 113: 616-620, 2001.
|
|
|
|
|
|
[PubMed: 11380446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2001.02786.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kundu, R. K., Sangiorgi, F., Wu, L.-Y., Kurachi, K., Anderson, W. F., Maxson, R., Gordon, E. M.
|
|
<strong>Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice.</strong>
|
|
Blood 92: 168-174, 1998.
|
|
|
|
|
|
[PubMed: 9639513]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K.
|
|
<strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.
|
|
|
|
|
|
[PubMed: 19416882]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0902191106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lascari, A. D., Hoak, J. C., Taylor, J. C.
|
|
<strong>Christmas disease in a girl.</strong>
|
|
Am. J. Dis. Child. 117: 585-588, 1969.
|
|
|
|
|
|
[PubMed: 5781711]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archpedi.1969.02100030587016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R.
|
|
<strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong>
|
|
Am. J. Hemat. 43: 177-182, 1993.
|
|
|
|
|
|
[PubMed: 8352232]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830430304]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, H., Haurigot, V., Doyon, Y., Li, T., Wong, S. Y., Bhagwat, A. S., Malani, N., Anguela, X. M., Sharma, R., Ivanciu, L., Murphy, S. L., Finn, J. D., Khazi, F. R., Zhou, S., Paschon, D. E., Rebar, E. J., Bushman, F. D., Gregory, P. D., Holmes, M. C., High, K. A.
|
|
<strong>In vivo genome editing restores haemostasis in a mouse model of haemophilia.</strong>
|
|
Nature 475: 217-221, 2011.
|
|
|
|
|
|
[PubMed: 21706032]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lillicrap, D. P., Liddell, M. B., Matthews, R. J., Peake, I. R., Bloom, A. L.
|
|
<strong>Comparison of phenotypic assessment and the use of two restriction fragment length polymorphisms in the diagnosis of the carrier state in haemophilia B.</strong>
|
|
Brit. J. Haemat. 62: 557-565, 1986.
|
|
|
|
|
|
[PubMed: 3006741]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1986.tb02968.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, J.-Z., Li, X., Drost, J., Thorland, E. C., Liu, Q., Lind, T., Roberts, S., Wang, H. Y., Sommer, S. S.
|
|
<strong>The human factor IX gene as germline mutagen test: samples from mainland China have the putatively endogenous pattern of mutation.</strong>
|
|
Hum. Mutat. 16: 31-36, 2000.
|
|
|
|
|
|
[PubMed: 10874302]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1098-1004(200007)16:1<31::AID-HUMU6>3.0.CO;2-I]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ljung, R., Petrini, P., Tengborn, L., Sjorin, E.
|
|
<strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong>
|
|
Brit. J. Haemat. 113: 81-86, 2001.
|
|
|
|
|
|
[PubMed: 11328285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2001.02759.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mandalaki, T., Louizou, C., Dimitriadou, C., Briet, E.
|
|
<strong>Haemophilia B Leyden in Greece.</strong>
|
|
Thromb. Haemost. 56: 340-342, 1986.
|
|
|
|
|
|
[PubMed: 3563965]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Manno, C. S., Chew, A. J., Hutchison, S., Larson, P. J., Herzog, R. W., Arruda, V. R., Tai, S. J., Ragni, M. V., Thompson, A., Ozelo, M., Couto, L. B., Leonard, D. G. B., Johnson, F. A., McClelland, A., Scallan, C., Skarsgard, E., Flake, A. W., Kay, M. A., High, K. A., Glader, B.
|
|
<strong>AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.</strong>
|
|
Blood 101: 2963-2972, 2003.
|
|
|
|
|
|
[PubMed: 12515715]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2002-10-3296]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L.
|
|
<strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong>
|
|
J. Clin. Invest. 79: 746-753, 1987.
|
|
|
|
|
|
[PubMed: 3029178]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112880]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Peake, I. R., Bloom, A. L., Anson, D. S.
|
|
<strong>Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene.</strong>
|
|
J. Med. Genet. 25: 779-780, 1988.
|
|
|
|
|
|
[PubMed: 2907054]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.25.11.779]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Kling, S., Nilsson, I. M., Giannelli, F.
|
|
<strong>Direct estimate of the haemophilia B (factor IX deficiency) mutation rate and of the ratio of the sex-specific mutation rates in Sweden.</strong>
|
|
Hum. Genet. 89: 319-322, 1992.
|
|
|
|
|
|
[PubMed: 1601423]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220550]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Nilsson, I. M., Giannelli, F.
|
|
<strong>Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD).</strong>
|
|
Hum. Genet. 85: 200-204, 1990.
|
|
|
|
|
|
[PubMed: 2370049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00193196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Giannelli, F., Bentley, D. R.
|
|
<strong>Direct detection of point mutations by mismatch analysis: application to haemophilia B.</strong>
|
|
Nucleic Acids Res. 17: 3347-3358, 1989.
|
|
|
|
|
|
[PubMed: 2726481]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/17.9.3347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., O'Beirne, J., Smith, K., and 20 others.
|
|
<strong>Adenovirus-associated virus vector-mediated gene transfer in hemophilia B.</strong>
|
|
New Eng. J. Med. 365: 2357-2365, 2011.
|
|
|
|
|
|
[PubMed: 22149959]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1108046]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Neal, W. R., Tayloe, D. T., Jr., Cederbaum, A. I., Roberts, H. R.
|
|
<strong>Detection of genetic variants of haemophilia B with an immunosorbent technique.</strong>
|
|
Brit. J. Haemat. 25: 63-68, 1973.
|
|
|
|
|
|
[PubMed: 4793126]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1973.tb01716.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Neuschatz, J., Necheles, T. F.
|
|
<strong>Hemophilia B in a phenotypically normal girl with XX (ring): XO mosaicism.</strong>
|
|
Acta Haemat. 49: 108-113, 1973.
|
|
|
|
|
|
[PubMed: 4196476]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000208391]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nisen, P., Stamberg, J., Ehrenpreis, R., Velasco, S., Shende, A., Engelberg, J., Karayalcin, G., Waber, L.
|
|
<strong>The molecular basis of severe hemophilia B in a girl.</strong>
|
|
New Eng. J. Med. 315: 1139-1142, 1986.
|
|
|
|
|
|
[PubMed: 3093864]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198610303151806]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nour-Eldin, F., Wilkinson, J. F.
|
|
<strong>Factor-VII deficiency with Christmas disease in one family.</strong>
|
|
Lancet 273: 1173-1176, 1959. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 13666001]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(59)91184-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orstavik, K. H., Stormorken, H., Sparr, T.
|
|
<strong>Hemophilia B(M) in a female.</strong>
|
|
Thromb. Res. 37: 561-566, 1985.
|
|
|
|
|
|
[PubMed: 3983911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0049-3848(85)90088-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orstavik, K. H., Veltkamp, J. J., Bertina, R. M., Hermans, J.
|
|
<strong>Detection of carriers of haemophilia B.</strong>
|
|
Brit. J. Haemat. 42: 293-301, 1979.
|
|
|
|
|
|
[PubMed: 465373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1979.tb01133.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Furlong, B. L., Bloom, A. L.
|
|
<strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong>
|
|
Lancet 323: 242-243, 1984. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 6142993]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(84)90123-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Matthews, R. J., Bloom, A. L.
|
|
<strong>Haemophilia B Chicago: severe haemophilia B caused by two deletions and an inversion within the factor IX gene.</strong>
|
|
Brit. J. Haemat. 71 (suppl. 1): 1, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pipe, S. W., Leebeek, F. W. G., Recht, M., Key, N. S., Castaman, G., Miesbach, W., Lattimore, S., Peerlinck, K., Van der Valk, P., Coppens, M., Kampmann, P., Meijer, K., and 26 others.
|
|
<strong>Gene therapy with etranacogene dezaparvovec for hemophilia B.</strong>
|
|
New Eng. J. Med. 388: 706-718, 2023.
|
|
|
|
|
|
[PubMed: 36812434]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa2211644]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Plug, I., Mauser-Bunschoten, E. P., Brocker-Vriends, A. H. J. T., van Amstel, H. K. P., van der Bom, J. G., van Diemen-Homan, J. E. M., Willemse, J., Rosendaal, F. R.
|
|
<strong>Bleeding in carriers of hemophilia.</strong>
|
|
Blood 108: 52-56, 2006.
|
|
|
|
|
|
[PubMed: 16551972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2005-09-3879]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poon, M.-C., Chui, D. H. K., Patterson, M., Starozik, D. M., Dimnik, L. S., Hoar, D. I.
|
|
<strong>Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes.</strong>
|
|
J. Clin. Invest. 79: 1204-1209, 1987.
|
|
|
|
|
|
[PubMed: 2881949]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112938]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poort, S. R., Briet, E., Bertina, R. M., Reitsma, P. H.
|
|
<strong>A Dutch pedigree with mild hemophilia B with a missense mutation in the first EGF domain [factor IX(Oud en Nieuw Gastel)].</strong>
|
|
Nucleic Acids Res. 17: 5869, 1989.
|
|
|
|
|
|
[PubMed: 2762170]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/17.14.5869]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Purrello, M., Alhadeff, B., Esposito, D., Szabo, P., Rocchi, M., Truett, M., Masiarz, F., Siniscalco, M.
|
|
<strong>The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.</strong>
|
|
EMBO J. 4: 725-729, 1985.
|
|
|
|
|
|
[PubMed: 3924593]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1985.tb03689.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E.
|
|
<strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong>
|
|
Blood 72: 1074, 1988.
|
|
|
|
|
|
[PubMed: 3416069]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roberts, H. R., Grizzle, J. E., McLester, W. D., Penick, G. D.
|
|
<strong>Genetic variants of hemophilia B: detection by means of a specific PTC inhibitor.</strong>
|
|
J. Clin. Invest. 47: 360-365, 1968.
|
|
|
|
|
|
[PubMed: 12066779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI105732]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rogaev, E. I., Grigorenko, A. P., Faskhutdinova, G., Kittler, E. L. W., Moliaka, Y. K.
|
|
<strong>Genotype analysis identifies the cause of the 'Royal disease.'</strong>
|
|
Science 326: 817 only, 2009.
|
|
|
|
|
|
[PubMed: 19815722]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1180660]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schnieke, A. E., Kind, A. J., Ritchie, W. A., Mycock, K., Scott, A. R., Ritchie, M., Wilmut, I., Colman, A., Campbell, K. H. S.
|
|
<strong>Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts.</strong>
|
|
Science 278: 2130-2133, 1997.
|
|
|
|
|
|
[PubMed: 9405350]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.278.5346.2130]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Siguret, V., Amselem, S., Vidaud, M., Assouline, Z., Kerbiriou-Nabias, D., Pietu, G., Goossens, M., Larrieu, M. J., Bahnak, B., Meyer, D., Lavergne, J. M.
|
|
<strong>Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.</strong>
|
|
Brit. J. Haemat. 70: 411-416, 1988.
|
|
|
|
|
|
[PubMed: 3219291]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb02509.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sommer, S. S., Bowie, E. J. W., Ketterling, R. P., Bottema, C. D. K.
|
|
<strong>Missense mutations and the magnitude of functional deficit: the example of factor IX.</strong>
|
|
Hum. Genet. 89: 295-297, 1992.
|
|
|
|
|
|
[PubMed: 1601420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220543]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soucie, J. M., Evatt, B., Jackson, D., Hemophilia Surveillance System Project Investigators.
|
|
<strong>Occurrence of hemophilia in the United States.</strong>
|
|
Am. J. Hemat. 59: 288-294, 1998.
|
|
|
|
|
|
[PubMed: 9840909]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8652(199812)59:4<288::aid-ajh4>3.0.co;2-i]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spinelli, A., Schmid, W., Straub, P. W.
|
|
<strong>Christmas disease (haemophilia B) in a girl with deletion of the short arm of one X-chromosome (functional Turner syndrome).</strong>
|
|
Brit. J. Haemat. 34: 129-135, 1976.
|
|
|
|
|
|
[PubMed: 952762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1976.tb00181.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Szabo, P., Purrello, M., Rocchi, M., Archidiacono, N., Alhadeff, B., Filippi, G., Toniolo, D., Martini, G., Luzzatto, L., Siniscalco, M.
|
|
<strong>Cytological mapping of the human glucose-6-phosphate dehydrogenase gene distal to the fragile-X site suggests a high rate of meiotic recombination across this site.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 7855-7859, 1984.
|
|
|
|
|
|
[PubMed: 6595664]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.81.24.7855]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H.
|
|
<strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong>
|
|
J. Lab. Clin. Med. 112: 307-313, 1988.
|
|
|
|
|
|
[PubMed: 3411192]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P.
|
|
<strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong>
|
|
Proc. Nat. Acad. Sci. 88: 39-42, 1991.
|
|
|
|
|
|
[PubMed: 1986380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.1.39]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Duffin, J., Cameron, C., Teitel, J., Garvey, B., Lillicrap, D. P.
|
|
<strong>Characterization of the original Christmas disease mutation (cysteine 206-to-serine): from clinical recognition to molecular pathogenesis.</strong>
|
|
Thromb. Haemost. 67: 63-65, 1992.
|
|
|
|
|
|
[PubMed: 1615485]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N.
|
|
<strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong>
|
|
Hum. Genet. 79: 273-276, 1988.
|
|
|
|
|
|
[PubMed: 2841226]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00366250]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A.
|
|
<strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong>
|
|
Scand. J. Haemat. 7: 82-90, 1970.
|
|
|
|
|
|
[PubMed: 5450691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0609.1970.tb01873.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verstraete, M., Vermylen, C., Vandenbroucke, J.
|
|
<strong>Hemophilia B associated with a decreased factor VII activity.</strong>
|
|
Am. J. Med. Sci. 243: 20-26, 1962.
|
|
|
|
|
|
[PubMed: 13925578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00000441-196201000-00003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vianna-Morgante, A. M., Batista, D. A. S., Levisky, R. B., Zatz, M.
|
|
<strong>X;autosome translocations in females with X-linked recessive diseases. (Abstract)</strong>
|
|
7th International Congress of Human Genetics, Berlin 1986. P. 97.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M.
|
|
<strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong>
|
|
Hum. Genet. 91: 241-244, 1993.
|
|
|
|
|
|
[PubMed: 8478007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00218264]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wadelius, C., Blomback, M., Pettersson, U.
|
|
<strong>Molecular studies of haemophilia B in Sweden: identification of patients with total deletion of the factor IX gene and without inhibitory antibodies.</strong>
|
|
Hum. Genet. 81: 13-17, 1988.
|
|
|
|
|
|
[PubMed: 2848757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00283721]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wadelius, C., Lindstedt, M., Pigg, M., Egberg, N., Pettersson, U., Anvret, M.
|
|
<strong>Hemophilia B in a 46,XX female probably caused by non-random X inactivation.</strong>
|
|
Clin. Genet. 43: 1-4, 1993.
|
|
|
|
|
|
[PubMed: 8096443]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1993.tb04415.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wall, R. L., McConnell, J., Moore, D., Macpherson, C. R., Marson, A.
|
|
<strong>Christmas disease, color-blindness and blood group Xg(a).</strong>
|
|
Am. J. Med. 43: 214-226, 1967.
|
|
|
|
|
|
[PubMed: 5298508]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(67)90166-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L., Zoppe, M., Hackeng, T. M., Griffin, J. H., Lee, K.-F., Verma, I. M.
|
|
<strong>A factor IX-deficient mouse model for hemophilia B gene therapy.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 11563-11566, 1997.
|
|
|
|
|
|
[PubMed: 9326649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.21.11563]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whittaker, D. L., Copeland, D. L., Graham, J. B.
|
|
<strong>Linkage of color blindness with hemophilias A and B.</strong>
|
|
Am. J. Hum. Genet. 14: 149-158, 1962.
|
|
|
|
|
|
[PubMed: 14006651]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winship, P. R., Rees, D. J. G., Alkan, M.
|
|
<strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong>
|
|
Lancet 333: 631-634, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 2564457]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)92141-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yant, S. R., Meuse, L., Chiu, W., Ivics, Z., Izsvak, Z., Kay, M. A.
|
|
<strong>Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system.</strong>
|
|
Nature Genet. 25: 35-41, 2000.
|
|
|
|
|
|
[PubMed: 10802653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/75568]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yao, S.-N., Wilson, J. M., Nabel, E. G., Kurachi, S., Hachiya, H. L., Kurachi, K.
|
|
<strong>Expression of human factor IX in rat capillary endothelial cells: toward somatic gene therapy for hemophilia B.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 8101-8105, 1991.
|
|
|
|
|
|
[PubMed: 1896457]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.18.8101]
|
|
|
|
|
|
</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">
|
|
Ada Hamosh - updated : 10/16/2024<br>Ada Hamosh - updated : 03/09/2023<br>Ada Hamosh - updated : 01/23/2018<br>Ada Hamosh - updated : 9/8/2014<br>Ada Hamosh - updated : 8/24/2011<br>Ada Hamosh - updated : 12/29/2009<br>Cassandra L. Kniffin - updated : 11/25/2009<br>Cassandra L. Kniffin - updated : 12/3/2008<br>Cassandra L. Kniffin - reorganized : 10/21/2008<br>Cassandra L. Kniffin - updated : 11/13/2007<br>Victor A. McKusick - updated : 1/11/2005<br>Victor A. McKusick - updated : 4/22/2004<br>Victor A. McKusick - updated : 9/4/2003<br>Victor A. McKusick - updated : 7/18/2003<br>Ada Hamosh - updated : 9/12/2002<br>Victor A. McKusick - updated : 9/20/2001<br>Victor A. McKusick - updated : 6/26/2001<br>Victor A. McKusick - updated : 6/22/2001<br>Victor A. McKusick - updated : 1/10/2001<br>Victor A. McKusick - updated : 9/22/2000<br>Victor A. McKusick - updated : 8/17/2000<br>Ada Hamosh - updated : 4/28/2000<br>Victor A. McKusick - updated : 3/1/2000<br>Victor A. McKusick - updated : 1/14/2000<br>Victor A. McKusick - updated : 1/13/2000<br>Victor A. McKusick - updated : 12/20/1999<br>Ada Hamosh - updated : 7/28/1999<br>Victor A. McKusick - updated : 2/14/1999<br>Victor A. McKusick - updated : 8/17/1998<br>Victor A. McKusick - updated : 7/13/1998<br>Victor A. McKusick - updated : 12/18/1997<br>Victor A. McKusick - updated : 11/6/1997<br>Victor A. McKusick - updated : 9/16/1997<br>Victor A. McKusick - updated : 3/21/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 10/16/2024<br>carol : 03/10/2023<br>alopez : 03/09/2023<br>alopez : 01/23/2018<br>carol : 10/17/2016<br>carol : 11/06/2014<br>alopez : 9/8/2014<br>alopez : 9/8/2014<br>terry : 2/29/2012<br>terry : 1/18/2012<br>alopez : 8/25/2011<br>terry : 8/24/2011<br>carol : 4/11/2011<br>carol : 4/7/2011<br>alopez : 1/5/2010<br>terry : 12/29/2009<br>wwang : 12/2/2009<br>carol : 12/2/2009<br>ckniffin : 11/25/2009<br>ckniffin : 11/25/2009<br>terry : 6/5/2009<br>terry : 4/9/2009<br>terry : 4/9/2009<br>wwang : 12/4/2008<br>ckniffin : 12/3/2008<br>terry : 11/19/2008<br>carol : 10/21/2008<br>ckniffin : 10/15/2008<br>carol : 10/9/2008<br>terry : 8/26/2008<br>wwang : 11/20/2007<br>ckniffin : 11/13/2007<br>carol : 11/27/2006<br>terry : 11/10/2005<br>wwang : 1/14/2005<br>wwang : 1/12/2005<br>terry : 1/11/2005<br>terry : 4/22/2004<br>alopez : 4/7/2004<br>carol : 3/17/2004<br>cwells : 9/30/2003<br>terry : 9/4/2003<br>tkritzer : 7/29/2003<br>terry : 7/18/2003<br>carol : 7/7/2003<br>alopez : 9/12/2002<br>cwells : 9/12/2002<br>mcapotos : 1/2/2002<br>mcapotos : 9/27/2001<br>terry : 9/20/2001<br>mcapotos : 7/5/2001<br>mcapotos : 7/5/2001<br>mcapotos : 6/26/2001<br>terry : 6/26/2001<br>terry : 6/22/2001<br>mcapotos : 3/27/2001<br>cwells : 1/17/2001<br>terry : 1/10/2001<br>mcapotos : 10/3/2000<br>mcapotos : 9/22/2000<br>carol : 8/18/2000<br>terry : 8/17/2000<br>alopez : 5/1/2000<br>terry : 4/28/2000<br>alopez : 3/1/2000<br>terry : 3/1/2000<br>mgross : 2/21/2000<br>terry : 1/14/2000<br>terry : 1/13/2000<br>carol : 12/27/1999<br>terry : 12/20/1999<br>terry : 9/21/1999<br>alopez : 7/30/1999<br>carol : 7/28/1999<br>kayiaros : 7/8/1999<br>kayiaros : 7/8/1999<br>carol : 2/14/1999<br>carol : 2/5/1999<br>psherman : 1/8/1999<br>dkim : 12/15/1998<br>dkim : 12/10/1998<br>dkim : 9/22/1998<br>dkim : 9/22/1998<br>carol : 8/18/1998<br>terry : 8/17/1998<br>dkim : 7/21/1998<br>carol : 7/16/1998<br>terry : 7/13/1998<br>alopez : 5/21/1998<br>mark : 12/18/1997<br>terry : 12/16/1997<br>terry : 11/13/1997<br>terry : 11/6/1997<br>mark : 9/22/1997<br>terry : 9/16/1997<br>terry : 9/16/1997<br>alopez : 7/29/1997<br>alopez : 7/8/1997<br>terry : 5/28/1997<br>terry : 3/21/1997<br>terry : 3/17/1997<br>mark : 11/12/1996<br>terry : 10/24/1996<br>mark : 7/22/1996<br>mark : 7/9/1996<br>mark : 3/30/1996<br>terry : 3/12/1996<br>mark : 12/20/1995<br>jason : 7/19/1994<br>carol : 5/23/1994<br>terry : 4/26/1994<br>warfield : 4/20/1994<br>mimadm : 4/15/1994<br>pfoster : 4/5/1994
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|