4109 lines
332 KiB
Text
4109 lines
332 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
|
|
|
|
- #142900 - HOLT-ORAM SYNDROME; HOS
|
|
|
|
|
|
- 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=142900"><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">#142900</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/142900"><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="#diagnosis">Diagnosis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cytogenetics">Cytogenetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</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="#nomenclature">Nomenclature</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=HOLT-ORAM SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=1023&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1111/" 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/3457" 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/holt-oram-syndrome" 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=142900[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=392" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/feb5ec20-7730-49a4-9ee1-8894a9e6bc06/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:0060468" 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/142900" 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/OMIA000839/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0060468" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div 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:142900" 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> 19092004<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q87.2<br />
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 392<br />
|
|
|
|
|
|
<strong>DO:</strong> 0060468<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>
|
|
142900
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HOLT-ORAM SYNDROME; HOS
|
|
|
|
</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">
|
|
HOS1<br />
|
|
HEART-HAND SYNDROME<br />
|
|
ATRIODIGITAL DYSPLASIA
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/12/842?start=-3&limit=10&highlight=842">
|
|
12q24.21
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Holt-Oram syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/142900"> 142900 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
TBX5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601620"> 601620 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/142900" 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/142900" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/142900" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Atrial septal defect (ostium secundum type) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204315000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204315000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.11</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0344724&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344724</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001684</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br /> -
|
|
Ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
|
|
Hypoplastic left heart syndrome <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62067003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62067003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q23.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q23.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/746.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">746.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152101&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152101</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004383" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004383</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Vascular </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Patent ductus arteriosus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83330001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83330001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q25.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q25.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/747.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">747.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013274&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013274</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CHEST </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> External Features </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Absent pectoralis major muscle <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4024213&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4024213</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009751</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009751</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Ribs Sternum Clavicles & Scapulae </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pectus excavatum or carinatum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230697</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000766" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000766</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000766" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000766</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Vertebral anomalies <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61367005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61367005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834129&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834129</a>, <a href="https://bioportal.bioontology.org/search?q=C0265343&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265343</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003468" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003468</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003468" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003468</a>]</span><br /> -
|
|
Thoracic scoliosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857790&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857790</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002943</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Limbs </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Absent thumb <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278811&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278811</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009777" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009777</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009777" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009777</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=802bce270b78159dd0b03a0ad6f2dc6f" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Hrd5CxQxSdGv4aWXKgqURtdVsrKpYtW_-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=802bce270b78159dd0b03a0ad6f2dc6f" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Bifid thumb <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/51219000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">51219000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4082168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4082168</a>, <a href="https://bioportal.bioontology.org/search?q=C0265608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265608</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009944</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009944</a>]</span><br /> -
|
|
Triphalangeal thumb <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205308004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205308004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q74.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q74.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241397&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241397</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001199" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001199</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001199" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001199</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=35de1477c268a6d42f86f25677a7609c" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/XR34kRDtve34dB3bQseXeWmKYcyc5kau-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=35de1477c268a6d42f86f25677a7609c" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Carpal bone anomalies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840535&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840535</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001191" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001191</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001191" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001191</a>]</span><br /> -
|
|
Upper extremity phocomelia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840536&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840536</a>]</span><br /> -
|
|
Radial-ulnar anomalies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840537&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840537</a>]</span><br /> -
|
|
Asymmetric involvement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840538&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840538</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</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 mutations in the T-Box 5 gene (TBX5, <a href="/entry/601620#0001">601620.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that Holt-Oram syndrome (HOS) is caused by heterozygous mutation in the TBX5 gene (<a href="/entry/601620">601620</a>) on chromosome 12q24.</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>Holt-Oram syndrome is an autosomal dominant disorder characterized by abnormalities of the upper limbs and shoulder girdle, associated with a congenital heart lesion. The typical combination is considered to be a triphalangeal thumb with a secundum atrial septal defect (ASD), but there is a great range in the severity of both the heart and skeletal lesions (summary by <a href="#17" class="mim-tip-reference" title="Hurst, J. A., Hall, C. M., Baraitser, M. <strong>The Holt-Oram syndrome.</strong> J. Med. Genet. 28: 406-410, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1870097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1870097</a>] [<a href="https://doi.org/10.1136/jmg.28.6.406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1870097">Hurst et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1870097" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Although the abnormality of the upper extremities is more extensive in some cases, the characteristic findings in the Holt-Oram syndrome are thumb anomaly and atrial septal defect. The thumb may be absent or may be a triphalangeal, nonopposable, finger-like digit. The thumb metacarpal has both a proximal and a distal epiphyseal ossification center (<a href="#39" class="mim-tip-reference" title="Temtamy, S. A., McKusick, V. A. <strong>The Genetics of Hand Malformations.</strong> New York: Alan R. Liss (pub.) 1978. Pp. 117-133."None>Temtamy and McKusick, 1978</a>).</p><p>This syndrome was first clearly described by <a href="#16" class="mim-tip-reference" title="Holt, M., Oram, S. <strong>Familial heart disease with skeletal malformations.</strong> Brit. Heart J. 22: 236-242, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14402857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14402857</a>] [<a href="https://doi.org/10.1136/hrt.22.2.236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14402857">Holt and Oram (1960)</a>, who observed atrial septal defect in members of 4 generations of a family, associated with 'a congenital anomaly of the thumbs which lay in the same plane as the fingers, their terminal phalanges being curved inwards.' <a href="#26" class="mim-tip-reference" title="McKusick, V. A. <strong>Medical genetics 1960.</strong> J. Chronic Dis. 14: 1-198, 1961. Fig. 45."None>McKusick (1961)</a> reported mother and daughter with atrial septal defect and absent or triphalangeal, fingerlike thumb. In 1966 the daughter gave birth to a male infant with upper extremity phocomelia and ventricular septal defect (VSD). The involvement of the arm was more extensive and the cardiovascular involvement more varied in the families described by <a href="#23" class="mim-tip-reference" title="Lewis, K. B., Bruce, R. A., Baum, D., Motulsky, A. G. <strong>The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis.</strong> JAMA 193: 1080-1086, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5896868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5896868</a>]" pmid="5896868">Lewis et al. (1965)</a> and <a href="#15" class="mim-tip-reference" title="Harris, L. C., Osborne, W. P. <strong>Congenital absence or hypoplasia of the radius with ventricular septal defect: ventriculo-radial dysplasia.</strong> J. Pediat. 68: 265-272, 1966."None>Harris and Osborne (1966)</a> than in the family of <a href="#16" class="mim-tip-reference" title="Holt, M., Oram, S. <strong>Familial heart disease with skeletal malformations.</strong> Brit. Heart J. 22: 236-242, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14402857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14402857</a>] [<a href="https://doi.org/10.1136/hrt.22.2.236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14402857">Holt and Oram (1960)</a>. However, it is not certain that these represented a separate mutation (<a href="#27" class="mim-tip-reference" title="McKusick, V. A. <strong>Personal Communication.</strong> Baltimore, Md. 1966."None>McKusick, 1966</a>). The family reported by <a href="#20" class="mim-tip-reference" title="Kuhn, E., Schaaf, J., Wagner, A. <strong>Primary pulmonary hypertension, congenital heart disease and skeletal anomalies in three generations.</strong> Jpn. Heart J. 4: 205-223, 1963."None>Kuhn et al. (1963)</a> may be an example of the Lewis type of heart-hand syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14402857+5896868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Lenz, W. <strong>Personal Communication.</strong> Munster, Germany 5/1968."None>Lenz (1968)</a> noted that the involvement of the arms in the Holt-Oram syndrome can be sufficiently severe to simulate thalidomide embryopathy.</p><p><a href="#4" class="mim-tip-reference" title="Boehme, D. H., Shotar, A. O. <strong>A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family.</strong> Clin. Genet. 36: 442-450, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2591070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2591070</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1989.tb03374.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2591070">Boehme and Shotar (1989)</a> described a Jordanian family of normal intelligence in which members of 3 generations had complex malformations of the arms combined with variably expressed congenital heart disease. Because of the pedigree pattern, which included 1 instance of male-to-male transmission, they suggested autosomal dominant inheritance, but concluded that the disorder was distinct from HOS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2591070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#32" class="mim-tip-reference" title="Poznanski, A. K., Gall, J. C., Jr., Stern, A. M. <strong>Skeletal manifestations of the Holt-Oram syndrome.</strong> Radiology 94: 45-54, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5410358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5410358</a>] [<a href="https://doi.org/10.1148/10.1148/94.1.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5410358">Poznanski et al. (1970)</a> pointed out that carpal abnormalities, e.g., extra carpal bones, are more specific for the Holt-Oram syndrome than are changes in the thumb. Posteriorly and laterally, protuberant medial epicondyles of the humerus were seen in several patients. The left side was more severely affected in 27 of 39 cases (<a href="#38" class="mim-tip-reference" title="Smith, A. T., Sack, G. H., Jr., Taylor, G. J. <strong>Holt-Oram syndrome.</strong> J. Pediat. 95: 538-543, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/480027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">480027</a>] [<a href="https://doi.org/10.1016/s0022-3476(79)80758-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="480027">Smith et al., 1979</a>). Cardiac involvement may be absent in patients with limb defects; 5 of 39 had normal clinical and EKG findings despite typical limb defects (<a href="#38" class="mim-tip-reference" title="Smith, A. T., Sack, G. H., Jr., Taylor, G. J. <strong>Holt-Oram syndrome.</strong> J. Pediat. 95: 538-543, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/480027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">480027</a>] [<a href="https://doi.org/10.1016/s0022-3476(79)80758-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="480027">Smith et al., 1979</a>). Although a secundum atrial septal defect is most common, a wide variety of other cardiac defects occur, including ventricular septal defects and mitral valve prolapse. Patients with only limb defects may bear offspring with the complete syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=480027+5410358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Glauser, T. A., Zackai, E., Weinberg, P., Clancy, R. <strong>Holt-Oram syndrome associated with the hypoplastic left heart syndrome.</strong> Clin. Genet. 36: 69-72, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2766565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2766565</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1989.tb03369.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2766565">Glauser et al. (1989)</a> described a family in which the father had atrial septal defect and a hypoplastic thumb, and a son had triphalangeal thumb and syndactyly of digits 1 and 2 on the left with aplasia of the right thumb, and hypoplastic left heart syndrome with large atrial septal defect, coarctation of the aorta, patent ductus arteriosus (PDA), severe aortic stenosis, small left ventricle, and pulmonary hypertension. An older sister of this son had atrial septal defect but no clinically or radiologically apparent abnormalities of the upper limbs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2766565" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Moens, P., De Smet, L., Fabry, G., Fryns, J. P. <strong>Holt-Oram syndrome: postaxial and central polydactyly as variable manifestation in a four generation family.</strong> Genet. Counsel. 4: 277-280, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8110414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8110414</a>]" pmid="8110414">Moens et al. (1993)</a> reported a 4-generation family with HOS. In addition to the typical changes in the thumb and atrial septal defect, there was postaxial/central polydactyly in some family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8110414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E. <strong>The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome).</strong> New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8114858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8114858</a>] [<a href="https://doi.org/10.1056/NEJM199403313301302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8114858">Basson et al. (1994)</a> reported 2 extensively affected kindreds with HOS showing linkage to chromosome 12. The first family was previously reported by <a href="#11" class="mim-tip-reference" title="Gall, J. C., Jr., Stern, A. M., Cohen, M. M., Adams, M. S., Davidson, R. T. <strong>Holt-Oram syndrome: clinical and genetic study of a large family.</strong> Am. J. Hum. Genet. 18: 187-200, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5904863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5904863</a>]" pmid="5904863">Gall et al. (1966)</a>. Of 49 at-risk family members in 5 generations, 26 (11 male and 15 female) were affected. Each affected member was the offspring of an affected parent, thereby confirming the high penetrance of the disease gene. All affected members had some skeletal abnormalities, although many of these were subtle and detected only by radiography. Skeletal deformities generally manifested as deformities of the thenar and carpal bones, occasionally in association with mildly hypoplastic clavicles and shortened radii. Thenar abnormalities included distal displacement of the thenar eminence in the presence or absence of a triphalangeal digit. Only one subject had an aplastic thumb on one side; the contralateral thumb was triphalangeal. None of the subjects had phocomelia or severe ectromelia. All affected members had cardiovascular disease. Septal defects were present in 15 of the surviving family members; 4 had atrial septal defects, 9 had ventricular septal defects, and 2 had both. The atrial septal defects were all of the ostium secundum type, except for one which involved an ostium primum defect. Four had required surgical correction of hemodynamically significant defects. One member of the family died of complications related to a complete atrioventricular canal defect. Eisenmenger syndrome, resulting from an uncorrected ventricular septal defect, was present in 1. Cardiac conduction disease, including bradycardia, atrioventricular block, atrial fibrillation, and sinus node dysfunction, was present in 11 of the surviving affected family members, and 6 required permanent pacemakers. The second family studied by <a href="#2" class="mim-tip-reference" title="Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E. <strong>The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome).</strong> New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8114858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8114858</a>] [<a href="https://doi.org/10.1056/NEJM199403313301302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8114858">Basson et al. (1994)</a> had 18 affected members (10 male and 8 female) surviving with HOS. All had skeletal abnormalities, which were typically more severe than those found in the first family. Bilateral frank phocomelia or severe ectromelia characterized by hypoplastic humeri, radii, and clavicles, with thenar aplasia and carpal and digital deformities, was present in 7. On the other hand, congenital cardiovascular disease was milder and less frequent in the second family in which 6 had cardiac disease, all consisting of atrial septal defect of the ostium secundum type. Surgery for the septal defect had been required in 3 of these. Only one member of the family had conduction disease (incomplete right bundle branch block), and none had patent ductus arteriosus or superior vena cava anomaly, which were present in members of the first kindred. Since the 2 families showed the same linkage relationship to markers on 12q, the disorders are probably due to different mutations in the same gene, which is important to the development of both the limbs and the cardiovascular system. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5904863+8114858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D. <strong>Holt-Oram syndrome: a clinical genetic study.</strong> J. Med. Genet. 33: 300-307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8730285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8730285</a>] [<a href="https://doi.org/10.1136/jmg.33.4.300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8730285">Newbury-Ecob et al. (1996)</a> reported a detailed study of a large cohort of patients that included 44 familial and 11 sporadic cases. Association of cardiac and radial abnormalities was a criterion for inclusion of familial cases. Limb defects were found in all affected persons. The thumb was the most commonly affected structure, although in 7 of 44 cases, the thumbs were normal. In most cases, the thumb defects (absence in 19/44, hypoplasia in 17/44, triphalangeal thumbs in 8/44) were associated with hypoplastic thenar or limited supination of the forearm. Radial hypoplasia (18/44) was more frequent than absence of radius (10/44). Ulnar hypoplasia occurred only in patients with radial defects. Most patients had narrow, sloping shoulders. Limb defects were always bilateral and often asymmetrical, the left side being more severely affected. Cardiac involvement was found in 95% of familial cases; secundum atrial septal defect (15) and ventricular septal defect (11) were the most common defects. In 17 of the familial cases, only ECG abnormalities were found. Both cardiac and limb abnormalities were more severe in the sporadic group. <a href="#29" class="mim-tip-reference" title="Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D. <strong>Holt-Oram syndrome: a clinical genetic study.</strong> J. Med. Genet. 33: 300-307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8730285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8730285</a>] [<a href="https://doi.org/10.1136/jmg.33.4.300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8730285">Newbury-Ecob et al. (1996)</a> found a significant positive correlation (r = 0.49) between severity of the limb and cardiac defects. The patients with atrial septal defects had more severe limb abnormalities. Correlation between sibs was greater than that between parent and offspring. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8730285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Sletten, L. J., Pierpont, M. E. M. <strong>Variation in severity of cardiac disease in Holt-Oram syndrome.</strong> Am. J. Med. Genet. 65: 128-132, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8911604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8911604</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19961016)65:2<128::AID-AJMG9>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8911604">Sletten and Pierpont (1996)</a> described a family in which the proband had hypoplastic left thumb, hypoplastic left ventricle and endocardial cushion defect. His mother, aunt, uncle, grandfather and some other relatives had less pronounced manifestations of HOS. Analysis of the literature showed that single cardiovascular malformations (CVM) such as ASD, VSD, or PDA were reported in 125 of 189 cases (66%), and 33 patients (17.5%) had more complex cardiac defects (hypoplastic left heart, total anomalous pulmonary venous return, truncus arteriosus). <a href="#37" class="mim-tip-reference" title="Sletten, L. J., Pierpont, M. E. M. <strong>Variation in severity of cardiac disease in Holt-Oram syndrome.</strong> Am. J. Med. Genet. 65: 128-132, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8911604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8911604</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19961016)65:2<128::AID-AJMG9>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8911604">Sletten and Pierpont (1996)</a> emphasized that the proportion of severe CVM in patients with HOS has been underestimated and should be considered in counseling families with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8911604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Kantaputra, P. N., Yamasaki, K., Ishida, T., Kishino, T., Niikawa, N. <strong>A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family.</strong> Am. J. Med. Genet. 111: 301-306, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210327</a>] [<a href="https://doi.org/10.1002/ajmg.10596" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12210327">Kantaputra et al. (2002)</a> described a Thai family in which the mother and 3 offspring were affected with a dominantly inherited malformation syndrome with short stature, upper limb anomaly, and minor craniofacial anomalies suggestive of HOS; however, molecular studies did not reveal any mutations in the TBX5 gene. One of the offspring, a 23-year-old man, was cardiologically asymptomatic, although echocardiography revealed he had a quadricuspid aortic valve associated with mild aortic regurgitation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Tseng, Y.-R., Su, Y.-N., Lu, F. L., Jeng, S.-F., Hsieh, W.-S., Chen, C.-Y., Chou, H.-C., Peng, S. S.-F. <strong>Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (Letter)</strong> Am. J. Med. Genet. 143A: 1012-1014, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17366586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17366586</a>] [<a href="https://doi.org/10.1002/ajmg.a.31672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17366586">Tseng et al. (2007)</a> reported a Taiwanese male infant with genetically confirmed HOS and right lung agenesis. He presented at birth with severe respiratory distress, sloping shoulder, and absence of bilateral thumbs and radii. Cardiac ultrasound showed atrial and ventricular septal defects, patent ductus arteriosus, and dextroposition of the heart. Chest CT scan showed absence of the right lung and bronchial tree. He also had absence of the right pulmonary artery and vein. <a href="#41" class="mim-tip-reference" title="Tseng, Y.-R., Su, Y.-N., Lu, F. L., Jeng, S.-F., Hsieh, W.-S., Chen, C.-Y., Chou, H.-C., Peng, S. S.-F. <strong>Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (Letter)</strong> Am. J. Med. Genet. 143A: 1012-1014, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17366586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17366586</a>] [<a href="https://doi.org/10.1002/ajmg.a.31672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17366586">Tseng et al. (2007)</a> noted that pulmonary anomalies are uncommon in HOS, but may expand the phenotypic abnormalities associated with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17366586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="diagnosis" class="mim-anchor"></a>
|
|
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Brons, J. T. J., Van Geijn, H. P., Wladimiroff, J. W., Van der Harten, J. J., Kwee, M. L., Sobotka-Plojhar, M., Arts, N. F. T. <strong>Prenatal ultrasound diagnosis of the Holt-Oram syndrome.</strong> Prenatal Diag. 8: 175-181, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3287365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3287365</a>] [<a href="https://doi.org/10.1002/pd.1970080303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3287365">Brons et al. (1988)</a> discussed the prenatal diagnosis of HOS in 2 pregnancies. More severe forms of the disorder were excluded early in gestation. In the first fetus, ventricular septal defect, atrial septal defect, and a minor skeletal defect were found at 22 weeks. In a second fetus in the same sibship, no structural abnormalities were discovered until the thirtieth week, when a small atrial septal defect was detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3287365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="cytogenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimCytogeneticsFold" id="mimCytogeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCytogeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCytogeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#34" class="mim-tip-reference" title="Rybak, M., Kozlowski, K., Kleczkowska, A., Lewandowska, J., Sokolowski, J., Soltysik-Wilk, E. <strong>Holt-Oram syndrome associated with ectromelia and chromosomal aberrations.</strong> Am. J. Dis. Child. 121: 490-495, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5581016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5581016</a>] [<a href="https://doi.org/10.1001/archpedi.1971.02100170072008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5581016">Rybak et al. (1971)</a> described many cases in 4 generations of a Polish family and concluded that partial deletion of the long arm of a B-group chromosome was related to the abnormality. They suggested that the single case of <a href="#30" class="mim-tip-reference" title="Ockey, C. H., Feldman, G. V., MacAulay, M. E., Delaney, M. J. <strong>A large deletion of the long arm of chromosome no. 4 in a child with limb abnormalities.</strong> Arch. Dis. Child. 42: 428-434, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4951642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4951642</a>] [<a href="https://doi.org/10.1136/adc.42.224.428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4951642">Ockey et al. (1967)</a> had the Holt-Oram syndrome; a similar deletion of the long arm of a group B chromosome was present. <a href="#35" class="mim-tip-reference" title="Rybak, M. <strong>Personal Communication.</strong> Krakow, Poland 9/7/1981."None>Rybak (1981)</a> reported that the family refused to be restudied with banding techniques. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4951642+5581016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#42" class="mim-tip-reference" title="Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M.-D., Arthuis, M., Jeanson, C. <strong>Two patients with interstitial del (14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin).</strong> Ann. Genet. 27: 237-240, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6335371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6335371</a>]" pmid="6335371">Turleau et al. (1984)</a> described de novo deletion of the q23-q24.2 region of chromosome 14 in a boy with arm and cardiac abnormalities possibly consistent with the Holt-Oram syndrome. In addition, he had mental retardation, synophrys, strabismus, thin upper lip, bilateral pretragian skin tags, and cryptorchidism. Using linkage studies, <a href="#33" class="mim-tip-reference" title="Ruiz, J. C., Legius, E., Cuppens, H., Moens, P., Marynen, P., Cassiman, J.-J. <strong>Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome.</strong> Clin. Genet. 46: 257-259, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7820941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7820941</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1994.tb04237.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7820941">Ruiz et al. (1994)</a> excluded the 14q23-q24 region as the site of the HOS gene in a Belgian family with several affected persons in 4 generations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6335371+7820941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Kristoffersson, U., Mineur, A., Heim, S., Mandahl, N., Mitelman, F. <strong>Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. (Letter)</strong> Am. J. Med. Genet. 28: 229-231, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3674114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3674114</a>] [<a href="https://doi.org/10.1002/ajmg.1320280135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3674114">Kristoffersson et al. (1987)</a> found normal high-resolution karyotypes in 3 patients: a mother, her daughter, and an unrelated woman. <a href="#45" class="mim-tip-reference" title="Yang, S. P., Sherman, S., Derstine, J. B., Schonberg, S. A. <strong>Holt-Oram syndrome gene may be on chromosome 20. (Abstract)</strong> Pediat. Res. 27: 137A only, 1990."None>Yang et al. (1990)</a> described a sporadic case of HOS associated with a de novo pericentric inversion of chromosome 20. The breakpoints in chromosome 20 were at p13 and q13.2. They suggested that the HOS mutation is located at the site of one of these breakpoints. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3674114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E. <strong>Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.</strong> Proc. Nat. Acad. Sci. 96: 2919-2924, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077612</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10077612[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.6.2919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10077612">Basson et al. (1999)</a> described a child with a chromosome 5;12 translocation that caused severe skeletal and composite cardiac malformations. The affected child had left arm phocomelia, right radial hypoplasia, and right thumb aplasia. Cardiac angiography demonstrated a common atrium and a complete atrioventricular canal defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10077612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#40" class="mim-tip-reference" title="Terrett, J. A., Newbury-Ecob, R., Cross, G. S., Fenton, I., Raeburn, J. A., Young, I. D., Brook, J. D. <strong>Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q.</strong> Nature Genet. 6: 401-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8054982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8054982</a>] [<a href="https://doi.org/10.1038/ng0494-401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8054982">Terrett et al. (1994)</a> studied linkage between microsatellite DNA markers and HOS in 7 families. In 5, linkage between HOS and markers on 12q was found, whereas the 2 remaining families, phenotypically indistinguishable from the others, did not show this linkage. Analysis of the family data with the computer program HOMOG indicated that HOS is a heterogeneous disorder. In the five 12q-linked families, <a href="#40" class="mim-tip-reference" title="Terrett, J. A., Newbury-Ecob, R., Cross, G. S., Fenton, I., Raeburn, J. A., Young, I. D., Brook, J. D. <strong>Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q.</strong> Nature Genet. 6: 401-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8054982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8054982</a>] [<a href="https://doi.org/10.1038/ng0494-401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8054982">Terrett et al. (1994)</a> narrowed the assignment to a 21-cM interval in the distal region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8054982" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 each of 2 extensively affected kindreds, <a href="#2" class="mim-tip-reference" title="Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E. <strong>The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome).</strong> New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8114858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8114858</a>] [<a href="https://doi.org/10.1056/NEJM199403313301302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8114858">Basson et al. (1994)</a> demonstrated linkage of HOS to markers in the 12q2 region; combined multipoint lod score = 16.8. Judging by the location of the markers used, HOS probably is in the q21.3-q22 region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8114858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#10" class="mim-tip-reference" title="Fryns, J. P., Bonnet, D., De Smet, L. <strong>Holt-Oram syndrome with associated postaxial and central polysyndactyly: further evidence for genetic heterogeneity in the Holt-Oram syndrome. (Letter)</strong> Genet. Counsel. 7: 323-324, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8985738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8985738</a>]" pmid="8985738">Fryns et al. (1996)</a> reported a family in which linkage to 12q was excluded, thus demonstrating genetic heterogeneity in the Holt-Oram syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8985738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>The Holt-Oram syndrome is inherited as an autosomal dominant trait (<a href="#17" class="mim-tip-reference" title="Hurst, J. A., Hall, C. M., Baraitser, M. <strong>The Holt-Oram syndrome.</strong> J. Med. Genet. 28: 406-410, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1870097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1870097</a>] [<a href="https://doi.org/10.1136/jmg.28.6.406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1870097">Hurst et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1870097" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Braulke, I., Herzog, S., Thies, U., Zoll, B. <strong>Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report.</strong> Clin. Genet. 39: 241-244, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2070544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2070544</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1991.tb03021.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2070544">Braulke et al. (1991)</a> reported a probable instance of germinal mosaicism: an unaffected man fathered 4 offspring with HOS by 3 different women. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2070544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#24" class="mim-tip-reference" title="Li, Q. Y., Newbury-Ecob, R. A., Terrett, J. A., Wilson, D. I., Curtis, A. R. J., Yi, C. H., Gebuhr, T., Bullen, P. J., Robson, S. C., Strachan, T., Bonnet, D., Lyonnet, S., Young, I. D., Raeburn, J. A., Buckler, A. J., Law, D. J., Brook, J. D. <strong>Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.</strong> Nature Genet. 15: 21-29, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988164</a>] [<a href="https://doi.org/10.1038/ng0197-21" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988164">Li et al. (1997)</a> and <a href="#1" class="mim-tip-reference" title="Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E. <strong>Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome.</strong> Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988165</a>] [<a href="https://doi.org/10.1038/ng0197-30" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988165">Basson et al. (1997)</a> demonstrated mutations in the TBX5 gene as the basis of Holt-Oram syndrome (see, e.g., <a href="/entry/601620#0001">601620.0001</a>-<a href="/entry/601620#0005">601620.0005</a>). The dominant phenotype of HOS appears to result from haploinsufficiency of TBX5. The glu69-to-ter mutation (<a href="/entry/601620#0002">601620.0002</a>) identified by <a href="#1" class="mim-tip-reference" title="Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E. <strong>Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome.</strong> Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988165</a>] [<a href="https://doi.org/10.1038/ng0197-30" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988165">Basson et al. (1997)</a> in affected members of one kindred was predicted to encode a markedly truncated TBX5 protein that lacked most T-box residues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8988165+8988164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E. <strong>Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.</strong> Proc. Nat. Acad. Sci. 96: 2919-2924, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077612</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10077612[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.6.2919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10077612">Basson et al. (1999)</a> showed that TBX5 mutations predicted to create null alleles caused substantial abnormalities in both limb and heart. In contrast, missense mutations of the TBX5 gene produced distinct phenotypes: gly80 to arg (<a href="/entry/601620#0004">601620.0004</a>) caused significant cardiac malformations but only minor skeletal abnormalities, whereas 2 mutations of codon 237, arg237 to gln (<a href="/entry/601620#0003">601620.0003</a>) and arg237 to trp (<a href="/entry/601620#0005">601620.0005</a>), caused extensive upper limb malformations but less significant cardiac abnormalities. They noted that residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA, whereas residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10077612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#44" class="mim-tip-reference" title="Yang, J., Hu, D., Xia, J., Yang, Y., Ying, B., Hu, J., Zhou, X. <strong>Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome.</strong> Am. J. Med. Genet. 92: 237-240, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10842287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10842287</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000605)92:4<237::aid-ajmg2>3.0.co;2-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10842287">Yang et al. (2000)</a> analyzed 11 Chinese patients with Holt-Oram syndrome using SSCP analysis of TBX5. The authors identified 3 novel mutations, including a frameshift mutation caused by a deletion of 1 basepair (<a href="/entry/601620#0006">601620.0006</a>), and 2 missense mutations (<a href="/entry/601620#0007">601620.0007</a> and <a href="/entry/601620#0008">601620.0008</a>). The patients with the frameshift mutation had more severe upper limb anomalies, including aplasia/hypoplasia of the arm and thumbs, while those with missense mutations had milder anomalies, such as absent or hypoplastic thumbs, without arm abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10842287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated families with HOS, <a href="#14" class="mim-tip-reference" title="Gruenauer-Kloevekorn, C., Froster, U. G. <strong>Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families.</strong> Ann. Genet. 46: 19-23, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12818525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12818525</a>] [<a href="https://doi.org/10.1016/s0003-3995(03)00006-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12818525">Gruenauer-Kloevekorn and Froster (2003)</a> found the same truncation mutation in all affected members (<a href="/entry/601620#0009">601620.0009</a>). The phenotype was similar in both families and included ASD, hypoplastic deltoid muscles, and hypoplastic or absent thumbs extending to radial defects in 1 patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12818525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J. <strong>Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes.</strong> Am. J. Med. Genet. 140A: 1880-1886, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16892408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16892408</a>] [<a href="https://doi.org/10.1002/ajmg.a.31340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16892408">Borozdin et al. (2006)</a> reported a Czech mother and 2 daughters who were diagnosed with Holt-Oram syndrome, in whom they identified a 2.19 to 2.27-Mb contiguous deletion encompassing the TBX5 and TBX3 (<a href="/entry/601621">601621</a>) genes. Clinical reexamination confirmed the presence of features of ulnar-mammary syndrome (UMS; <a href="/entry/181450">181450</a>) that were previously unrecognized. <a href="#5" class="mim-tip-reference" title="Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J. <strong>Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes.</strong> Am. J. Med. Genet. 140A: 1880-1886, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16892408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16892408</a>] [<a href="https://doi.org/10.1002/ajmg.a.31340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16892408">Borozdin et al. (2006)</a> noted that the contiguous deletion also included the RBM19 gene (<a href="/entry/616444">616444</a>), but commented that it was unlikely to contribute to or modify the phenotype since all the anomalies present in the affected individuals could be explained by either TBX5 or TBX3 haploinsufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16892408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 5-generation family segregating an atypical form of HOS, consisting predominantly of nonseptal cardiac defects and mild limb anomalies, <a href="#31" class="mim-tip-reference" title="Patel, C., Silcock, L., McMullan, D., Brueton, L., Cox, H. <strong>TBX5 intragenic duplication: a family with atypical Holt-Oram syndrome phenotype.</strong> Europ. J. Hum. Genet. 20: 863-86, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22333898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22333898</a>] [<a href="https://doi.org/10.1038/ejhg.2012.16" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22333898">Patel et al. (2012)</a> identified a 48-kb duplication encompassing exons 2 through 9 of the TBX5 gene. The duplication, which was identified by array CGH and multiplex ligation-dependent probe amplification, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22333898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="nomenclature" class="mim-anchor"></a>
|
|
<h4 href="#mimNomenclatureFold" id="mimNomenclatureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimNomenclatureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimNomenclatureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#26" class="mim-tip-reference" title="McKusick, V. A. <strong>Medical genetics 1960.</strong> J. Chronic Dis. 14: 1-198, 1961. Fig. 45."None>McKusick (1961)</a> suggested the alternative designations atriodigital dysplasia and Holt-Oram syndrome; the latter 'caught on.'</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>An obituary of Samuel Oram (1913-1991) was provided by <a href="#8" class="mim-tip-reference" title="Davies, P. <strong>Obituary: S. Oram, MD, FRCP.</strong> Brit. Med. J. 304: 500 only, 1992."None>Davies (1992)</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="#Emerit1965" class="mim-tip-reference" title="Emerit, I., de Grouchy, J., Laval-Jeantet, M., Corone, P., Vernant, P. <strong>Malformations complexes des membres superieurs associees a une cardiopathie congenitale. A propos de six observations.</strong> Acta Genet. Med. Gemellol. 14: 132-163, 1965.">Emerit et al. (1965)</a>; <a href="#Gladstone1982" class="mim-tip-reference" title="Gladstone, I., Jr., Sybert, V. P. <strong>Holt-Oram syndrome: penetrance of the gene and lack of maternal effect.</strong> Clin. Genet. 21: 98-103, 1982.">Gladstone and Sybert (1982)</a>; <a href="#Letts1976" class="mim-tip-reference" title="Letts, R. M., Chudley, A. E., Cumming, G., Shokeir, M. H. <strong>The upper limb-cardiovascular syndrome (Holt-Oram syndrome).</strong> Clin. Orthop. Relat. Res. 116: 149-154, 1976.">Letts et al.
|
|
(1976)</a>; <a href="#Mcfarland1980" class="mim-tip-reference" title="Mcfarland, J. C., Fallon, J. T. <strong>Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1980.</strong> New Eng. J. Med. 303: 1519-1526, 1980.">Mcfarland and Fallon (1980)</a>; <a href="#Sahn1981" class="mim-tip-reference" title="Sahn, D. J., Goldberg, S. J., Allen, H. D., Canale, J. M. <strong>Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome.</strong> Chest 79: 113-115, 1981.">Sahn et al. (1981)</a>; <a href="#Van1982" class="mim-tip-reference" title="Van Regemorter, N., Haumont, D., Kirkpatrick, C., Viseur, P., Jeanty, P., Dodion, J., Milaire, J., Rooze, M., Rodesch, F. <strong>Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations.</strong> Europ. J. Pediat. 138: 77-80, 1982.">Van
|
|
Regemorter et al. (1982)</a>; <a href="#Zetterqvist1963" class="mim-tip-reference" title="Zetterqvist, P. <strong>The syndrome of familial atrial septal defect, heart arrhythmia and hand malformation (Holt-Oram) in mother and son.</strong> Acta Paediat. 52: 115-122, 1963.">Zetterqvist (1963)</a>; <a href="#Zhang1986" class="mim-tip-reference" title="Zhang, K.-Z., Sun, Q.-B., Cheng, T. O. <strong>Holt-Oram syndrome in China: a collective review of 18 cases.</strong> Am. Heart J. 111: 572-577, 1986.">Zhang et al. (1986)</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="Basson1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E.
|
|
<strong>Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome.</strong>
|
|
Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988165</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8988165" target="_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/ng0197-30" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Basson1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E.
|
|
<strong>The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome).</strong>
|
|
New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8114858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8114858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8114858" target="_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/NEJM199403313301302" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Basson1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E.
|
|
<strong>Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 2919-2924, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077612</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10077612[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=10077612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.6.2919" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Boehme1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boehme, D. H., Shotar, A. O.
|
|
<strong>A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family.</strong>
|
|
Clin. Genet. 36: 442-450, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2591070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2591070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2591070" target="_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.1399-0004.1989.tb03374.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Borozdin2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J.
|
|
<strong>Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes.</strong>
|
|
Am. J. Med. Genet. 140A: 1880-1886, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16892408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16892408</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16892408" target="_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.31340" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Braulke1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Braulke, I., Herzog, S., Thies, U., Zoll, B.
|
|
<strong>Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report.</strong>
|
|
Clin. Genet. 39: 241-244, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2070544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2070544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2070544" target="_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.1399-0004.1991.tb03021.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Brons1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brons, J. T. J., Van Geijn, H. P., Wladimiroff, J. W., Van der Harten, J. J., Kwee, M. L., Sobotka-Plojhar, M., Arts, N. F. T.
|
|
<strong>Prenatal ultrasound diagnosis of the Holt-Oram syndrome.</strong>
|
|
Prenatal Diag. 8: 175-181, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3287365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3287365</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3287365" target="_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/pd.1970080303" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Davies1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davies, P.
|
|
<strong>Obituary: S. Oram, MD, FRCP.</strong>
|
|
Brit. Med. J. 304: 500 only, 1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Emerit1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Emerit, I., de Grouchy, J., Laval-Jeantet, M., Corone, P., Vernant, P.
|
|
<strong>Malformations complexes des membres superieurs associees a une cardiopathie congenitale. A propos de six observations.</strong>
|
|
Acta Genet. Med. Gemellol. 14: 132-163, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14346078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14346078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14346078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Fryns1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fryns, J. P., Bonnet, D., De Smet, L.
|
|
<strong>Holt-Oram syndrome with associated postaxial and central polysyndactyly: further evidence for genetic heterogeneity in the Holt-Oram syndrome. (Letter)</strong>
|
|
Genet. Counsel. 7: 323-324, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8985738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8985738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8985738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Gall1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gall, J. C., Jr., Stern, A. M., Cohen, M. M., Adams, M. S., Davidson, R. T.
|
|
<strong>Holt-Oram syndrome: clinical and genetic study of a large family.</strong>
|
|
Am. J. Hum. Genet. 18: 187-200, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5904863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5904863</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5904863" 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="12" class="mim-anchor"></a>
|
|
<a id="Gladstone1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gladstone, I., Jr., Sybert, V. P.
|
|
<strong>Holt-Oram syndrome: penetrance of the gene and lack of maternal effect.</strong>
|
|
Clin. Genet. 21: 98-103, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7083616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7083616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7083616" target="_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.1399-0004.1982.tb00743.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Glauser1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Glauser, T. A., Zackai, E., Weinberg, P., Clancy, R.
|
|
<strong>Holt-Oram syndrome associated with the hypoplastic left heart syndrome.</strong>
|
|
Clin. Genet. 36: 69-72, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2766565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2766565</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2766565" target="_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.1399-0004.1989.tb03369.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Gruenauer-Kloevekorn2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gruenauer-Kloevekorn, C., Froster, U. G.
|
|
<strong>Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families.</strong>
|
|
Ann. Genet. 46: 19-23, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12818525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12818525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12818525" target="_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/s0003-3995(03)00006-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Harris1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harris, L. C., Osborne, W. P.
|
|
<strong>Congenital absence or hypoplasia of the radius with ventricular septal defect: ventriculo-radial dysplasia.</strong>
|
|
J. Pediat. 68: 265-272, 1966.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Holt1960" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holt, M., Oram, S.
|
|
<strong>Familial heart disease with skeletal malformations.</strong>
|
|
Brit. Heart J. 22: 236-242, 1960.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14402857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14402857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14402857" target="_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/hrt.22.2.236" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Hurst1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hurst, J. A., Hall, C. M., Baraitser, M.
|
|
<strong>The Holt-Oram syndrome.</strong>
|
|
J. Med. Genet. 28: 406-410, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1870097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1870097</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1870097" target="_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.28.6.406" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kantaputra2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kantaputra, P. N., Yamasaki, K., Ishida, T., Kishino, T., Niikawa, N.
|
|
<strong>A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family.</strong>
|
|
Am. J. Med. Genet. 111: 301-306, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210327</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210327" target="_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.10596" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kristoffersson1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kristoffersson, U., Mineur, A., Heim, S., Mandahl, N., Mitelman, F.
|
|
<strong>Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. (Letter)</strong>
|
|
Am. J. Med. Genet. 28: 229-231, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3674114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3674114</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3674114" target="_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.1320280135" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Kuhn1963" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kuhn, E., Schaaf, J., Wagner, A.
|
|
<strong>Primary pulmonary hypertension, congenital heart disease and skeletal anomalies in three generations.</strong>
|
|
Jpn. Heart J. 4: 205-223, 1963.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Lenz1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lenz, W.
|
|
<strong>Personal Communication.</strong>
|
|
Munster, Germany 5/1968.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Letts1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Letts, R. M., Chudley, A. E., Cumming, G., Shokeir, M. H.
|
|
<strong>The upper limb-cardiovascular syndrome (Holt-Oram syndrome).</strong>
|
|
Clin. Orthop. Relat. Res. 116: 149-154, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1277635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1277635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1277635" 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="Lewis1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lewis, K. B., Bruce, R. A., Baum, D., Motulsky, A. G.
|
|
<strong>The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis.</strong>
|
|
JAMA 193: 1080-1086, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5896868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5896868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5896868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Li1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, Q. Y., Newbury-Ecob, R. A., Terrett, J. A., Wilson, D. I., Curtis, A. R. J., Yi, C. H., Gebuhr, T., Bullen, P. J., Robson, S. C., Strachan, T., Bonnet, D., Lyonnet, S., Young, I. D., Raeburn, J. A., Buckler, A. J., Law, D. J., Brook, J. D.
|
|
<strong>Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.</strong>
|
|
Nature Genet. 15: 21-29, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8988164" target="_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/ng0197-21" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Mcfarland1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mcfarland, J. C., Fallon, J. T.
|
|
<strong>Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1980.</strong>
|
|
New Eng. J. Med. 303: 1519-1526, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7432422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7432422</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7432422" target="_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/NEJM198012253032608" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="McKusick1961" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A.
|
|
<strong>Medical genetics 1960.</strong>
|
|
J. Chronic Dis. 14: 1-198, 1961. Fig. 45.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="McKusick1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 1966.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Moens1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moens, P., De Smet, L., Fabry, G., Fryns, J. P.
|
|
<strong>Holt-Oram syndrome: postaxial and central polydactyly as variable manifestation in a four generation family.</strong>
|
|
Genet. Counsel. 4: 277-280, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8110414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8110414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8110414" 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="Newbury-Ecob1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D.
|
|
<strong>Holt-Oram syndrome: a clinical genetic study.</strong>
|
|
J. Med. Genet. 33: 300-307, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8730285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8730285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8730285" target="_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.33.4.300" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Ockey1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ockey, C. H., Feldman, G. V., MacAulay, M. E., Delaney, M. J.
|
|
<strong>A large deletion of the long arm of chromosome no. 4 in a child with limb abnormalities.</strong>
|
|
Arch. Dis. Child. 42: 428-434, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4951642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4951642</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4951642" target="_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/adc.42.224.428" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Patel2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Patel, C., Silcock, L., McMullan, D., Brueton, L., Cox, H.
|
|
<strong>TBX5 intragenic duplication: a family with atypical Holt-Oram syndrome phenotype.</strong>
|
|
Europ. J. Hum. Genet. 20: 863-86, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22333898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22333898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22333898" target="_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/ejhg.2012.16" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Poznanski1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poznanski, A. K., Gall, J. C., Jr., Stern, A. M.
|
|
<strong>Skeletal manifestations of the Holt-Oram syndrome.</strong>
|
|
Radiology 94: 45-54, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5410358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5410358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5410358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1148/10.1148/94.1.45" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Ruiz1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruiz, J. C., Legius, E., Cuppens, H., Moens, P., Marynen, P., Cassiman, J.-J.
|
|
<strong>Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome.</strong>
|
|
Clin. Genet. 46: 257-259, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7820941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7820941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7820941" target="_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.1399-0004.1994.tb04237.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Rybak1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rybak, M., Kozlowski, K., Kleczkowska, A., Lewandowska, J., Sokolowski, J., Soltysik-Wilk, E.
|
|
<strong>Holt-Oram syndrome associated with ectromelia and chromosomal aberrations.</strong>
|
|
Am. J. Dis. Child. 121: 490-495, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5581016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5581016</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5581016" target="_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.1971.02100170072008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Rybak1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rybak, M.
|
|
<strong>Personal Communication.</strong>
|
|
Krakow, Poland 9/7/1981.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Sahn1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sahn, D. J., Goldberg, S. J., Allen, H. D., Canale, J. M.
|
|
<strong>Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome.</strong>
|
|
Chest 79: 113-115, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7449488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7449488</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7449488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1378/chest.79.1.113" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Sletten1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sletten, L. J., Pierpont, M. E. M.
|
|
<strong>Variation in severity of cardiac disease in Holt-Oram syndrome.</strong>
|
|
Am. J. Med. Genet. 65: 128-132, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8911604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8911604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8911604" target="_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)1096-8628(19961016)65:2<128::AID-AJMG9>3.0.CO;2-O" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Smith1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Smith, A. T., Sack, G. H., Jr., Taylor, G. J.
|
|
<strong>Holt-Oram syndrome.</strong>
|
|
J. Pediat. 95: 538-543, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/480027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">480027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=480027" target="_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/s0022-3476(79)80758-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Temtamy1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Temtamy, S. A., McKusick, V. A.
|
|
<strong>The Genetics of Hand Malformations.</strong>
|
|
New York: Alan R. Liss (pub.) 1978. Pp. 117-133.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Terrett1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Terrett, J. A., Newbury-Ecob, R., Cross, G. S., Fenton, I., Raeburn, J. A., Young, I. D., Brook, J. D.
|
|
<strong>Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q.</strong>
|
|
Nature Genet. 6: 401-404, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8054982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8054982</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8054982" target="_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/ng0494-401" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Tseng2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tseng, Y.-R., Su, Y.-N., Lu, F. L., Jeng, S.-F., Hsieh, W.-S., Chen, C.-Y., Chou, H.-C., Peng, S. S.-F.
|
|
<strong>Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (Letter)</strong>
|
|
Am. J. Med. Genet. 143A: 1012-1014, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17366586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17366586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17366586" target="_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.31672" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Turleau1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M.-D., Arthuis, M., Jeanson, C.
|
|
<strong>Two patients with interstitial del (14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin).</strong>
|
|
Ann. Genet. 27: 237-240, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6335371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6335371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6335371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Van Regemorter1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Regemorter, N., Haumont, D., Kirkpatrick, C., Viseur, P., Jeanty, P., Dodion, J., Milaire, J., Rooze, M., Rodesch, F.
|
|
<strong>Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations.</strong>
|
|
Europ. J. Pediat. 138: 77-80, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7075631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7075631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7075631" target="_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/BF00442335" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Yang2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yang, J., Hu, D., Xia, J., Yang, Y., Ying, B., Hu, J., Zhou, X.
|
|
<strong>Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome.</strong>
|
|
Am. J. Med. Genet. 92: 237-240, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10842287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10842287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10842287" target="_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)1096-8628(20000605)92:4<237::aid-ajmg2>3.0.co;2-g" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Yang1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yang, S. P., Sherman, S., Derstine, J. B., Schonberg, S. A.
|
|
<strong>Holt-Oram syndrome gene may be on chromosome 20. (Abstract)</strong>
|
|
Pediat. Res. 27: 137A only, 1990.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Zetterqvist1963" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zetterqvist, P.
|
|
<strong>The syndrome of familial atrial septal defect, heart arrhythmia and hand malformation (Holt-Oram) in mother and son.</strong>
|
|
Acta Paediat. 52: 115-122, 1963.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14003500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14003500</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14003500" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1651-2227.1963.tb04085.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Zhang1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, K.-Z., Sun, Q.-B., Cheng, T. O.
|
|
<strong>Holt-Oram syndrome in China: a collective review of 18 cases.</strong>
|
|
Am. Heart J. 111: 572-577, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3953367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3953367</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3953367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-8703(86)90066-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 10/18/2006
|
|
</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">
|
|
Carol A. Bocchini - updated : 9/14/2006<br>Victor A. McKusick - updated : 9/24/2002<br>Sonja A. Rasmussen - updated : 7/13/2000<br>Victor A. McKusick - updated : 4/16/1999<br>Victor A. McKusick - updated : 2/7/1997<br>Iosif W. Lurie - updated : 1/14/1997<br>Iosif W. Lurie - updated : 9/7/1996<br>Iosif W. Lurie - updated : 6/26/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 04/16/2018
|
|
</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 : 03/07/2018<br>carol : 03/06/2018<br>carol : 09/28/2016<br>carol : 09/27/2016<br>mgross : 06/30/2015<br>terry : 12/21/2012<br>terry : 5/10/2012<br>carol : 9/20/2010<br>wwang : 7/29/2009<br>terry : 6/3/2009<br>wwang : 7/19/2007<br>ckniffin : 7/17/2007<br>wwang : 10/20/2006<br>terry : 10/18/2006<br>carol : 9/14/2006<br>wwang : 10/18/2005<br>ckniffin : 4/30/2004<br>mgross : 12/10/2002<br>tkritzer : 9/24/2002<br>mcapotos : 7/19/2000<br>mcapotos : 7/17/2000<br>mcapotos : 7/14/2000<br>mcapotos : 7/13/2000<br>mgross : 4/27/1999<br>mgross : 4/21/1999<br>terry : 4/16/1999<br>alopez : 7/30/1998<br>alopez : 7/29/1997<br>terry : 7/7/1997<br>joanna : 7/7/1997<br>terry : 6/21/1997<br>terry : 2/7/1997<br>terry : 2/3/1997<br>mark : 1/15/1997<br>jenny : 1/14/1997<br>jenny : 1/8/1997<br>randy : 9/7/1996<br>carol : 6/26/1996<br>davew : 8/18/1994<br>mimadm : 5/17/1994<br>carol : 5/3/1994<br>pfoster : 4/20/1994<br>carol : 6/28/1993<br>carol : 5/5/1992
|
|
</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> 142900
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HOLT-ORAM SYNDROME; HOS
|
|
|
|
</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">
|
|
HOS1<br />
|
|
HEART-HAND SYNDROME<br />
|
|
ATRIODIGITAL DYSPLASIA
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 19092004;
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q87.2;
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 392;
|
|
|
|
|
|
<strong>DO:</strong> 0060468;
|
|
|
|
|
|
</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">
|
|
12q24.21
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Holt-Oram syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
142900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
TBX5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601620
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that Holt-Oram syndrome (HOS) is caused by heterozygous mutation in the TBX5 gene (601620) on chromosome 12q24.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Holt-Oram syndrome is an autosomal dominant disorder characterized by abnormalities of the upper limbs and shoulder girdle, associated with a congenital heart lesion. The typical combination is considered to be a triphalangeal thumb with a secundum atrial septal defect (ASD), but there is a great range in the severity of both the heart and skeletal lesions (summary by Hurst et al., 1991). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Although the abnormality of the upper extremities is more extensive in some cases, the characteristic findings in the Holt-Oram syndrome are thumb anomaly and atrial septal defect. The thumb may be absent or may be a triphalangeal, nonopposable, finger-like digit. The thumb metacarpal has both a proximal and a distal epiphyseal ossification center (Temtamy and McKusick, 1978).</p><p>This syndrome was first clearly described by Holt and Oram (1960), who observed atrial septal defect in members of 4 generations of a family, associated with 'a congenital anomaly of the thumbs which lay in the same plane as the fingers, their terminal phalanges being curved inwards.' McKusick (1961) reported mother and daughter with atrial septal defect and absent or triphalangeal, fingerlike thumb. In 1966 the daughter gave birth to a male infant with upper extremity phocomelia and ventricular septal defect (VSD). The involvement of the arm was more extensive and the cardiovascular involvement more varied in the families described by Lewis et al. (1965) and Harris and Osborne (1966) than in the family of Holt and Oram (1960). However, it is not certain that these represented a separate mutation (McKusick, 1966). The family reported by Kuhn et al. (1963) may be an example of the Lewis type of heart-hand syndrome. </p><p>Lenz (1968) noted that the involvement of the arms in the Holt-Oram syndrome can be sufficiently severe to simulate thalidomide embryopathy.</p><p>Boehme and Shotar (1989) described a Jordanian family of normal intelligence in which members of 3 generations had complex malformations of the arms combined with variably expressed congenital heart disease. Because of the pedigree pattern, which included 1 instance of male-to-male transmission, they suggested autosomal dominant inheritance, but concluded that the disorder was distinct from HOS. </p><p>Poznanski et al. (1970) pointed out that carpal abnormalities, e.g., extra carpal bones, are more specific for the Holt-Oram syndrome than are changes in the thumb. Posteriorly and laterally, protuberant medial epicondyles of the humerus were seen in several patients. The left side was more severely affected in 27 of 39 cases (Smith et al., 1979). Cardiac involvement may be absent in patients with limb defects; 5 of 39 had normal clinical and EKG findings despite typical limb defects (Smith et al., 1979). Although a secundum atrial septal defect is most common, a wide variety of other cardiac defects occur, including ventricular septal defects and mitral valve prolapse. Patients with only limb defects may bear offspring with the complete syndrome. </p><p>Glauser et al. (1989) described a family in which the father had atrial septal defect and a hypoplastic thumb, and a son had triphalangeal thumb and syndactyly of digits 1 and 2 on the left with aplasia of the right thumb, and hypoplastic left heart syndrome with large atrial septal defect, coarctation of the aorta, patent ductus arteriosus (PDA), severe aortic stenosis, small left ventricle, and pulmonary hypertension. An older sister of this son had atrial septal defect but no clinically or radiologically apparent abnormalities of the upper limbs. </p><p>Moens et al. (1993) reported a 4-generation family with HOS. In addition to the typical changes in the thumb and atrial septal defect, there was postaxial/central polydactyly in some family members. </p><p>Basson et al. (1994) reported 2 extensively affected kindreds with HOS showing linkage to chromosome 12. The first family was previously reported by Gall et al. (1966). Of 49 at-risk family members in 5 generations, 26 (11 male and 15 female) were affected. Each affected member was the offspring of an affected parent, thereby confirming the high penetrance of the disease gene. All affected members had some skeletal abnormalities, although many of these were subtle and detected only by radiography. Skeletal deformities generally manifested as deformities of the thenar and carpal bones, occasionally in association with mildly hypoplastic clavicles and shortened radii. Thenar abnormalities included distal displacement of the thenar eminence in the presence or absence of a triphalangeal digit. Only one subject had an aplastic thumb on one side; the contralateral thumb was triphalangeal. None of the subjects had phocomelia or severe ectromelia. All affected members had cardiovascular disease. Septal defects were present in 15 of the surviving family members; 4 had atrial septal defects, 9 had ventricular septal defects, and 2 had both. The atrial septal defects were all of the ostium secundum type, except for one which involved an ostium primum defect. Four had required surgical correction of hemodynamically significant defects. One member of the family died of complications related to a complete atrioventricular canal defect. Eisenmenger syndrome, resulting from an uncorrected ventricular septal defect, was present in 1. Cardiac conduction disease, including bradycardia, atrioventricular block, atrial fibrillation, and sinus node dysfunction, was present in 11 of the surviving affected family members, and 6 required permanent pacemakers. The second family studied by Basson et al. (1994) had 18 affected members (10 male and 8 female) surviving with HOS. All had skeletal abnormalities, which were typically more severe than those found in the first family. Bilateral frank phocomelia or severe ectromelia characterized by hypoplastic humeri, radii, and clavicles, with thenar aplasia and carpal and digital deformities, was present in 7. On the other hand, congenital cardiovascular disease was milder and less frequent in the second family in which 6 had cardiac disease, all consisting of atrial septal defect of the ostium secundum type. Surgery for the septal defect had been required in 3 of these. Only one member of the family had conduction disease (incomplete right bundle branch block), and none had patent ductus arteriosus or superior vena cava anomaly, which were present in members of the first kindred. Since the 2 families showed the same linkage relationship to markers on 12q, the disorders are probably due to different mutations in the same gene, which is important to the development of both the limbs and the cardiovascular system. </p><p>Newbury-Ecob et al. (1996) reported a detailed study of a large cohort of patients that included 44 familial and 11 sporadic cases. Association of cardiac and radial abnormalities was a criterion for inclusion of familial cases. Limb defects were found in all affected persons. The thumb was the most commonly affected structure, although in 7 of 44 cases, the thumbs were normal. In most cases, the thumb defects (absence in 19/44, hypoplasia in 17/44, triphalangeal thumbs in 8/44) were associated with hypoplastic thenar or limited supination of the forearm. Radial hypoplasia (18/44) was more frequent than absence of radius (10/44). Ulnar hypoplasia occurred only in patients with radial defects. Most patients had narrow, sloping shoulders. Limb defects were always bilateral and often asymmetrical, the left side being more severely affected. Cardiac involvement was found in 95% of familial cases; secundum atrial septal defect (15) and ventricular septal defect (11) were the most common defects. In 17 of the familial cases, only ECG abnormalities were found. Both cardiac and limb abnormalities were more severe in the sporadic group. Newbury-Ecob et al. (1996) found a significant positive correlation (r = 0.49) between severity of the limb and cardiac defects. The patients with atrial septal defects had more severe limb abnormalities. Correlation between sibs was greater than that between parent and offspring. </p><p>Sletten and Pierpont (1996) described a family in which the proband had hypoplastic left thumb, hypoplastic left ventricle and endocardial cushion defect. His mother, aunt, uncle, grandfather and some other relatives had less pronounced manifestations of HOS. Analysis of the literature showed that single cardiovascular malformations (CVM) such as ASD, VSD, or PDA were reported in 125 of 189 cases (66%), and 33 patients (17.5%) had more complex cardiac defects (hypoplastic left heart, total anomalous pulmonary venous return, truncus arteriosus). Sletten and Pierpont (1996) emphasized that the proportion of severe CVM in patients with HOS has been underestimated and should be considered in counseling families with the disorder. </p><p>Kantaputra et al. (2002) described a Thai family in which the mother and 3 offspring were affected with a dominantly inherited malformation syndrome with short stature, upper limb anomaly, and minor craniofacial anomalies suggestive of HOS; however, molecular studies did not reveal any mutations in the TBX5 gene. One of the offspring, a 23-year-old man, was cardiologically asymptomatic, although echocardiography revealed he had a quadricuspid aortic valve associated with mild aortic regurgitation. </p><p>Tseng et al. (2007) reported a Taiwanese male infant with genetically confirmed HOS and right lung agenesis. He presented at birth with severe respiratory distress, sloping shoulder, and absence of bilateral thumbs and radii. Cardiac ultrasound showed atrial and ventricular septal defects, patent ductus arteriosus, and dextroposition of the heart. Chest CT scan showed absence of the right lung and bronchial tree. He also had absence of the right pulmonary artery and vein. Tseng et al. (2007) noted that pulmonary anomalies are uncommon in HOS, but may expand the phenotypic abnormalities associated with the disorder. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Brons et al. (1988) discussed the prenatal diagnosis of HOS in 2 pregnancies. More severe forms of the disorder were excluded early in gestation. In the first fetus, ventricular septal defect, atrial septal defect, and a minor skeletal defect were found at 22 weeks. In a second fetus in the same sibship, no structural abnormalities were discovered until the thirtieth week, when a small atrial septal defect was detected. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Rybak et al. (1971) described many cases in 4 generations of a Polish family and concluded that partial deletion of the long arm of a B-group chromosome was related to the abnormality. They suggested that the single case of Ockey et al. (1967) had the Holt-Oram syndrome; a similar deletion of the long arm of a group B chromosome was present. Rybak (1981) reported that the family refused to be restudied with banding techniques. </p><p>Turleau et al. (1984) described de novo deletion of the q23-q24.2 region of chromosome 14 in a boy with arm and cardiac abnormalities possibly consistent with the Holt-Oram syndrome. In addition, he had mental retardation, synophrys, strabismus, thin upper lip, bilateral pretragian skin tags, and cryptorchidism. Using linkage studies, Ruiz et al. (1994) excluded the 14q23-q24 region as the site of the HOS gene in a Belgian family with several affected persons in 4 generations. </p><p>Kristoffersson et al. (1987) found normal high-resolution karyotypes in 3 patients: a mother, her daughter, and an unrelated woman. Yang et al. (1990) described a sporadic case of HOS associated with a de novo pericentric inversion of chromosome 20. The breakpoints in chromosome 20 were at p13 and q13.2. They suggested that the HOS mutation is located at the site of one of these breakpoints. </p><p>Basson et al. (1999) described a child with a chromosome 5;12 translocation that caused severe skeletal and composite cardiac malformations. The affected child had left arm phocomelia, right radial hypoplasia, and right thumb aplasia. Cardiac angiography demonstrated a common atrium and a complete atrioventricular canal defect. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Terrett et al. (1994) studied linkage between microsatellite DNA markers and HOS in 7 families. In 5, linkage between HOS and markers on 12q was found, whereas the 2 remaining families, phenotypically indistinguishable from the others, did not show this linkage. Analysis of the family data with the computer program HOMOG indicated that HOS is a heterogeneous disorder. In the five 12q-linked families, Terrett et al. (1994) narrowed the assignment to a 21-cM interval in the distal region. </p><p>In each of 2 extensively affected kindreds, Basson et al. (1994) demonstrated linkage of HOS to markers in the 12q2 region; combined multipoint lod score = 16.8. Judging by the location of the markers used, HOS probably is in the q21.3-q22 region. </p><p>Fryns et al. (1996) reported a family in which linkage to 12q was excluded, thus demonstrating genetic heterogeneity in the Holt-Oram syndrome. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The Holt-Oram syndrome is inherited as an autosomal dominant trait (Hurst et al., 1991). </p><p>Braulke et al. (1991) reported a probable instance of germinal mosaicism: an unaffected man fathered 4 offspring with HOS by 3 different women. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Li et al. (1997) and Basson et al. (1997) demonstrated mutations in the TBX5 gene as the basis of Holt-Oram syndrome (see, e.g., 601620.0001-601620.0005). The dominant phenotype of HOS appears to result from haploinsufficiency of TBX5. The glu69-to-ter mutation (601620.0002) identified by Basson et al. (1997) in affected members of one kindred was predicted to encode a markedly truncated TBX5 protein that lacked most T-box residues. </p><p>Basson et al. (1999) showed that TBX5 mutations predicted to create null alleles caused substantial abnormalities in both limb and heart. In contrast, missense mutations of the TBX5 gene produced distinct phenotypes: gly80 to arg (601620.0004) caused significant cardiac malformations but only minor skeletal abnormalities, whereas 2 mutations of codon 237, arg237 to gln (601620.0003) and arg237 to trp (601620.0005), caused extensive upper limb malformations but less significant cardiac abnormalities. They noted that residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA, whereas residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA. </p><p>Yang et al. (2000) analyzed 11 Chinese patients with Holt-Oram syndrome using SSCP analysis of TBX5. The authors identified 3 novel mutations, including a frameshift mutation caused by a deletion of 1 basepair (601620.0006), and 2 missense mutations (601620.0007 and 601620.0008). The patients with the frameshift mutation had more severe upper limb anomalies, including aplasia/hypoplasia of the arm and thumbs, while those with missense mutations had milder anomalies, such as absent or hypoplastic thumbs, without arm abnormalities. </p><p>In 2 unrelated families with HOS, Gruenauer-Kloevekorn and Froster (2003) found the same truncation mutation in all affected members (601620.0009). The phenotype was similar in both families and included ASD, hypoplastic deltoid muscles, and hypoplastic or absent thumbs extending to radial defects in 1 patient. </p><p>Borozdin et al. (2006) reported a Czech mother and 2 daughters who were diagnosed with Holt-Oram syndrome, in whom they identified a 2.19 to 2.27-Mb contiguous deletion encompassing the TBX5 and TBX3 (601621) genes. Clinical reexamination confirmed the presence of features of ulnar-mammary syndrome (UMS; 181450) that were previously unrecognized. Borozdin et al. (2006) noted that the contiguous deletion also included the RBM19 gene (616444), but commented that it was unlikely to contribute to or modify the phenotype since all the anomalies present in the affected individuals could be explained by either TBX5 or TBX3 haploinsufficiency. </p><p>In affected members of a 5-generation family segregating an atypical form of HOS, consisting predominantly of nonseptal cardiac defects and mild limb anomalies, Patel et al. (2012) identified a 48-kb duplication encompassing exons 2 through 9 of the TBX5 gene. The duplication, which was identified by array CGH and multiplex ligation-dependent probe amplification, segregated with the disorder in the family. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>McKusick (1961) suggested the alternative designations atriodigital dysplasia and Holt-Oram syndrome; the latter 'caught on.'</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>An obituary of Samuel Oram (1913-1991) was provided by Davies (1992).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Emerit et al. (1965); Gladstone and Sybert (1982); Letts et al.
|
|
(1976); Mcfarland and Fallon (1980); Sahn et al. (1981); Van
|
|
Regemorter et al. (1982); Zetterqvist (1963); Zhang et al. (1986)
|
|
</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">
|
|
Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E.
|
|
<strong>Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome.</strong>
|
|
Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997.
|
|
|
|
|
|
[PubMed: 8988165]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0197-30]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E.
|
|
<strong>The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome).</strong>
|
|
New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994.
|
|
|
|
|
|
[PubMed: 8114858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199403313301302]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E.
|
|
<strong>Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 2919-2924, 1999.
|
|
|
|
|
|
[PubMed: 10077612]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.6.2919]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boehme, D. H., Shotar, A. O.
|
|
<strong>A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family.</strong>
|
|
Clin. Genet. 36: 442-450, 1989.
|
|
|
|
|
|
[PubMed: 2591070]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb03374.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J.
|
|
<strong>Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes.</strong>
|
|
Am. J. Med. Genet. 140A: 1880-1886, 2006.
|
|
|
|
|
|
[PubMed: 16892408]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31340]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Braulke, I., Herzog, S., Thies, U., Zoll, B.
|
|
<strong>Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report.</strong>
|
|
Clin. Genet. 39: 241-244, 1991.
|
|
|
|
|
|
[PubMed: 2070544]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1991.tb03021.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brons, J. T. J., Van Geijn, H. P., Wladimiroff, J. W., Van der Harten, J. J., Kwee, M. L., Sobotka-Plojhar, M., Arts, N. F. T.
|
|
<strong>Prenatal ultrasound diagnosis of the Holt-Oram syndrome.</strong>
|
|
Prenatal Diag. 8: 175-181, 1988.
|
|
|
|
|
|
[PubMed: 3287365]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/pd.1970080303]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davies, P.
|
|
<strong>Obituary: S. Oram, MD, FRCP.</strong>
|
|
Brit. Med. J. 304: 500 only, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Emerit, I., de Grouchy, J., Laval-Jeantet, M., Corone, P., Vernant, P.
|
|
<strong>Malformations complexes des membres superieurs associees a une cardiopathie congenitale. A propos de six observations.</strong>
|
|
Acta Genet. Med. Gemellol. 14: 132-163, 1965.
|
|
|
|
|
|
[PubMed: 14346078]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fryns, J. P., Bonnet, D., De Smet, L.
|
|
<strong>Holt-Oram syndrome with associated postaxial and central polysyndactyly: further evidence for genetic heterogeneity in the Holt-Oram syndrome. (Letter)</strong>
|
|
Genet. Counsel. 7: 323-324, 1996.
|
|
|
|
|
|
[PubMed: 8985738]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gall, J. C., Jr., Stern, A. M., Cohen, M. M., Adams, M. S., Davidson, R. T.
|
|
<strong>Holt-Oram syndrome: clinical and genetic study of a large family.</strong>
|
|
Am. J. Hum. Genet. 18: 187-200, 1966.
|
|
|
|
|
|
[PubMed: 5904863]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gladstone, I., Jr., Sybert, V. P.
|
|
<strong>Holt-Oram syndrome: penetrance of the gene and lack of maternal effect.</strong>
|
|
Clin. Genet. 21: 98-103, 1982.
|
|
|
|
|
|
[PubMed: 7083616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1982.tb00743.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Glauser, T. A., Zackai, E., Weinberg, P., Clancy, R.
|
|
<strong>Holt-Oram syndrome associated with the hypoplastic left heart syndrome.</strong>
|
|
Clin. Genet. 36: 69-72, 1989.
|
|
|
|
|
|
[PubMed: 2766565]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb03369.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gruenauer-Kloevekorn, C., Froster, U. G.
|
|
<strong>Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families.</strong>
|
|
Ann. Genet. 46: 19-23, 2003.
|
|
|
|
|
|
[PubMed: 12818525]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0003-3995(03)00006-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harris, L. C., Osborne, W. P.
|
|
<strong>Congenital absence or hypoplasia of the radius with ventricular septal defect: ventriculo-radial dysplasia.</strong>
|
|
J. Pediat. 68: 265-272, 1966.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holt, M., Oram, S.
|
|
<strong>Familial heart disease with skeletal malformations.</strong>
|
|
Brit. Heart J. 22: 236-242, 1960.
|
|
|
|
|
|
[PubMed: 14402857]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/hrt.22.2.236]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hurst, J. A., Hall, C. M., Baraitser, M.
|
|
<strong>The Holt-Oram syndrome.</strong>
|
|
J. Med. Genet. 28: 406-410, 1991.
|
|
|
|
|
|
[PubMed: 1870097]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.28.6.406]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kantaputra, P. N., Yamasaki, K., Ishida, T., Kishino, T., Niikawa, N.
|
|
<strong>A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family.</strong>
|
|
Am. J. Med. Genet. 111: 301-306, 2002.
|
|
|
|
|
|
[PubMed: 12210327]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.10596]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kristoffersson, U., Mineur, A., Heim, S., Mandahl, N., Mitelman, F.
|
|
<strong>Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. (Letter)</strong>
|
|
Am. J. Med. Genet. 28: 229-231, 1987.
|
|
|
|
|
|
[PubMed: 3674114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320280135]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kuhn, E., Schaaf, J., Wagner, A.
|
|
<strong>Primary pulmonary hypertension, congenital heart disease and skeletal anomalies in three generations.</strong>
|
|
Jpn. Heart J. 4: 205-223, 1963.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lenz, W.
|
|
<strong>Personal Communication.</strong>
|
|
Munster, Germany 5/1968.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Letts, R. M., Chudley, A. E., Cumming, G., Shokeir, M. H.
|
|
<strong>The upper limb-cardiovascular syndrome (Holt-Oram syndrome).</strong>
|
|
Clin. Orthop. Relat. Res. 116: 149-154, 1976.
|
|
|
|
|
|
[PubMed: 1277635]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lewis, K. B., Bruce, R. A., Baum, D., Motulsky, A. G.
|
|
<strong>The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis.</strong>
|
|
JAMA 193: 1080-1086, 1965.
|
|
|
|
|
|
[PubMed: 5896868]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, Q. Y., Newbury-Ecob, R. A., Terrett, J. A., Wilson, D. I., Curtis, A. R. J., Yi, C. H., Gebuhr, T., Bullen, P. J., Robson, S. C., Strachan, T., Bonnet, D., Lyonnet, S., Young, I. D., Raeburn, J. A., Buckler, A. J., Law, D. J., Brook, J. D.
|
|
<strong>Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.</strong>
|
|
Nature Genet. 15: 21-29, 1997.
|
|
|
|
|
|
[PubMed: 8988164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0197-21]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mcfarland, J. C., Fallon, J. T.
|
|
<strong>Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1980.</strong>
|
|
New Eng. J. Med. 303: 1519-1526, 1980.
|
|
|
|
|
|
[PubMed: 7432422]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198012253032608]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A.
|
|
<strong>Medical genetics 1960.</strong>
|
|
J. Chronic Dis. 14: 1-198, 1961. Fig. 45.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 1966.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moens, P., De Smet, L., Fabry, G., Fryns, J. P.
|
|
<strong>Holt-Oram syndrome: postaxial and central polydactyly as variable manifestation in a four generation family.</strong>
|
|
Genet. Counsel. 4: 277-280, 1993.
|
|
|
|
|
|
[PubMed: 8110414]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D.
|
|
<strong>Holt-Oram syndrome: a clinical genetic study.</strong>
|
|
J. Med. Genet. 33: 300-307, 1996.
|
|
|
|
|
|
[PubMed: 8730285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.33.4.300]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ockey, C. H., Feldman, G. V., MacAulay, M. E., Delaney, M. J.
|
|
<strong>A large deletion of the long arm of chromosome no. 4 in a child with limb abnormalities.</strong>
|
|
Arch. Dis. Child. 42: 428-434, 1967.
|
|
|
|
|
|
[PubMed: 4951642]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.42.224.428]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Patel, C., Silcock, L., McMullan, D., Brueton, L., Cox, H.
|
|
<strong>TBX5 intragenic duplication: a family with atypical Holt-Oram syndrome phenotype.</strong>
|
|
Europ. J. Hum. Genet. 20: 863-86, 2012.
|
|
|
|
|
|
[PubMed: 22333898]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2012.16]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poznanski, A. K., Gall, J. C., Jr., Stern, A. M.
|
|
<strong>Skeletal manifestations of the Holt-Oram syndrome.</strong>
|
|
Radiology 94: 45-54, 1970.
|
|
|
|
|
|
[PubMed: 5410358]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1148/10.1148/94.1.45]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruiz, J. C., Legius, E., Cuppens, H., Moens, P., Marynen, P., Cassiman, J.-J.
|
|
<strong>Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome.</strong>
|
|
Clin. Genet. 46: 257-259, 1994.
|
|
|
|
|
|
[PubMed: 7820941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1994.tb04237.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rybak, M., Kozlowski, K., Kleczkowska, A., Lewandowska, J., Sokolowski, J., Soltysik-Wilk, E.
|
|
<strong>Holt-Oram syndrome associated with ectromelia and chromosomal aberrations.</strong>
|
|
Am. J. Dis. Child. 121: 490-495, 1971.
|
|
|
|
|
|
[PubMed: 5581016]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archpedi.1971.02100170072008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rybak, M.
|
|
<strong>Personal Communication.</strong>
|
|
Krakow, Poland 9/7/1981.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sahn, D. J., Goldberg, S. J., Allen, H. D., Canale, J. M.
|
|
<strong>Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome.</strong>
|
|
Chest 79: 113-115, 1981.
|
|
|
|
|
|
[PubMed: 7449488]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1378/chest.79.1.113]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sletten, L. J., Pierpont, M. E. M.
|
|
<strong>Variation in severity of cardiac disease in Holt-Oram syndrome.</strong>
|
|
Am. J. Med. Genet. 65: 128-132, 1996.
|
|
|
|
|
|
[PubMed: 8911604]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961016)65:2<128::AID-AJMG9>3.0.CO;2-O]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Smith, A. T., Sack, G. H., Jr., Taylor, G. J.
|
|
<strong>Holt-Oram syndrome.</strong>
|
|
J. Pediat. 95: 538-543, 1979.
|
|
|
|
|
|
[PubMed: 480027]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(79)80758-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Temtamy, S. A., McKusick, V. A.
|
|
<strong>The Genetics of Hand Malformations.</strong>
|
|
New York: Alan R. Liss (pub.) 1978. Pp. 117-133.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Terrett, J. A., Newbury-Ecob, R., Cross, G. S., Fenton, I., Raeburn, J. A., Young, I. D., Brook, J. D.
|
|
<strong>Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q.</strong>
|
|
Nature Genet. 6: 401-404, 1994.
|
|
|
|
|
|
[PubMed: 8054982]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0494-401]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tseng, Y.-R., Su, Y.-N., Lu, F. L., Jeng, S.-F., Hsieh, W.-S., Chen, C.-Y., Chou, H.-C., Peng, S. S.-F.
|
|
<strong>Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (Letter)</strong>
|
|
Am. J. Med. Genet. 143A: 1012-1014, 2007.
|
|
|
|
|
|
[PubMed: 17366586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31672]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M.-D., Arthuis, M., Jeanson, C.
|
|
<strong>Two patients with interstitial del (14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin).</strong>
|
|
Ann. Genet. 27: 237-240, 1984.
|
|
|
|
|
|
[PubMed: 6335371]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Regemorter, N., Haumont, D., Kirkpatrick, C., Viseur, P., Jeanty, P., Dodion, J., Milaire, J., Rooze, M., Rodesch, F.
|
|
<strong>Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations.</strong>
|
|
Europ. J. Pediat. 138: 77-80, 1982.
|
|
|
|
|
|
[PubMed: 7075631]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00442335]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, J., Hu, D., Xia, J., Yang, Y., Ying, B., Hu, J., Zhou, X.
|
|
<strong>Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome.</strong>
|
|
Am. J. Med. Genet. 92: 237-240, 2000.
|
|
|
|
|
|
[PubMed: 10842287]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(20000605)92:4<237::aid-ajmg2>3.0.co;2-g]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, S. P., Sherman, S., Derstine, J. B., Schonberg, S. A.
|
|
<strong>Holt-Oram syndrome gene may be on chromosome 20. (Abstract)</strong>
|
|
Pediat. Res. 27: 137A only, 1990.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zetterqvist, P.
|
|
<strong>The syndrome of familial atrial septal defect, heart arrhythmia and hand malformation (Holt-Oram) in mother and son.</strong>
|
|
Acta Paediat. 52: 115-122, 1963.
|
|
|
|
|
|
[PubMed: 14003500]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1963.tb04085.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, K.-Z., Sun, Q.-B., Cheng, T. O.
|
|
<strong>Holt-Oram syndrome in China: a collective review of 18 cases.</strong>
|
|
Am. Heart J. 111: 572-577, 1986.
|
|
|
|
|
|
[PubMed: 3953367]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-8703(86)90066-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 10/18/2006<br>Carol A. Bocchini - updated : 9/14/2006<br>Victor A. McKusick - updated : 9/24/2002<br>Sonja A. Rasmussen - updated : 7/13/2000<br>Victor A. McKusick - updated : 4/16/1999<br>Victor A. McKusick - updated : 2/7/1997<br>Iosif W. Lurie - updated : 1/14/1997<br>Iosif W. Lurie - updated : 9/7/1996<br>Iosif W. Lurie - updated : 6/26/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 04/16/2018<br>carol : 03/07/2018<br>carol : 03/06/2018<br>carol : 09/28/2016<br>carol : 09/27/2016<br>mgross : 06/30/2015<br>terry : 12/21/2012<br>terry : 5/10/2012<br>carol : 9/20/2010<br>wwang : 7/29/2009<br>terry : 6/3/2009<br>wwang : 7/19/2007<br>ckniffin : 7/17/2007<br>wwang : 10/20/2006<br>terry : 10/18/2006<br>carol : 9/14/2006<br>wwang : 10/18/2005<br>ckniffin : 4/30/2004<br>mgross : 12/10/2002<br>tkritzer : 9/24/2002<br>mcapotos : 7/19/2000<br>mcapotos : 7/17/2000<br>mcapotos : 7/14/2000<br>mcapotos : 7/13/2000<br>mgross : 4/27/1999<br>mgross : 4/21/1999<br>terry : 4/16/1999<br>alopez : 7/30/1998<br>alopez : 7/29/1997<br>terry : 7/7/1997<br>joanna : 7/7/1997<br>terry : 6/21/1997<br>terry : 2/7/1997<br>terry : 2/3/1997<br>mark : 1/15/1997<br>jenny : 1/14/1997<br>jenny : 1/8/1997<br>randy : 9/7/1996<br>carol : 6/26/1996<br>davew : 8/18/1994<br>mimadm : 5/17/1994<br>carol : 5/3/1994<br>pfoster : 4/20/1994<br>carol : 6/28/1993<br>carol : 5/5/1992
|
|
</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>
|
|
|
|
|