4610 lines
373 KiB
Text
4610 lines
373 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
|
|
|
|
- *238331 - DIHYDROLIPOAMIDE DEHYDROGENASE; DLD
|
|
|
|
|
|
- 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=238331"><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">*238331</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/238331">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000091140;t=ENST00000205402" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=1738" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=238331" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000091140;t=ENST00000205402" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000108,NM_001289750,NM_001289751,NM_001289752" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000108" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=238331" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=02006&isoform_id=02006_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/DLD" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/181551,181575,307137,1339989,17391426,17391514,51095146,62088986,91199540,119603827,119603828,189065428,194376652,194379142,194387110,194390238,269849557,308219374,576583534,576583539,576583544" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/P09622" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=1738" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000091140;t=ENST00000205402" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=DLD" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=DLD" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+1738" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/DLD" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:1738" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/1738" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr7&hgg_gene=ENST00000205402.10&hgg_start=107891107&hgg_end=107921198&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2898" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/dld" 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=238331[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=238331[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/DLD/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000091140" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=DLD" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=DLD" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=DLD" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DLD&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA27352" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:2898" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:107450" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/DLD#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:107450" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/1738/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=1738" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00010794;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-040120-4" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1738" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=DLD&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 124184009, 767497003<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> D74.0<br />
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
238331
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
DIHYDROLIPOAMIDE DEHYDROGENASE; DLD
|
|
|
|
</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">
|
|
PYRUVATE DEHYDROGENASE COMPONENT E3; PHE3; E3<br />
|
|
BRANCHED CHAIN ALPHA-KETO ACID DEHYDROGENASE COMPLEX, E3 COMPONENT<br />
|
|
LIPOAMIDE REDUCTASE<br />
|
|
LIPOAMIDE DEHYDROGENASE; LAD; LADH<br />
|
|
LIPOYL DEHYDROGENASE<br />
|
|
DIHYDROLIPOYL DEHYDROGENASE<br />
|
|
DIAPHORASE<br />
|
|
GLYCINE CLEAVAGE SYSTEM L PROTEIN; GCSL
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DLD" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DLD</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/7/583?start=-3&limit=10&highlight=583">7q31.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:107891107-107921198&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">7:107,891,107-107,921,198</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/583?start=-3&limit=10&highlight=583">
|
|
7q31.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Dihydrolipoamide dehydrogenase deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/246900"> 246900 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/238331" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/238331" 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>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The DLD gene encodes dihydrolipoamide dehydrogenase (<a href="https://enzyme.expasy.org/EC/1.8.1.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.8.1.4</a>), a flavoprotein component known as E3 that is common to the 3 alpha-ketoacid dehydrogenase multienzyme complexes, namely, pyruvate dehydrogenase complex (PDC), the alpha-ketoglutarate dehydrogenase complex (KGDC), and the branched-chain alpha-keto acid dehydrogenase complex (BCKDC). The enzyme is a functional homodimer of the DLD protein and catalyzes the oxidative regeneration of a lipoic acid cofactor covalently bound to E2 (DBT; <a href="/entry/248610">248610</a>) yielding NADH. The DLD enzyme is also a component, referred to as the L protein, of the mitochondrial glycine cleavage system (GCS; <a href="https://enzyme.expasy.org/EC/2.1.2.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.1.2.10</a>). In addition, DLD has cryptic activities as a diaphorase and a serine protease (summary by <a href="#11" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. <strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong> Hum. Molec. Genet. 5: 1925-1930, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968745</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968745">Hong et al., 1996</a> and <a href="#27" class="mim-tip-reference" title="Vaubel, R. A., Rustin, P., Isaya, G. <strong>Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells.</strong> J. Biol. Chem. 286: 40232-40245, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21930696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21930696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21930696[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M111.274415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21930696">Vaubel et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8968745+21930696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Using a cDNA corresponding to lipoamide dehydrogenase isolated from a porcine adrenal medulla library, <a href="#17" class="mim-tip-reference" title="Otulakowski, G., Robinson, B. H. <strong>Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase.</strong> J. Biol. Chem. 262: 17313-17318, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3693355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3693355</a>]" pmid="3693355">Otulakowski and Robinson (1987)</a> isolated the corresponding human cDNA. The deduced amino acid sequence shows 96% identity to the porcine protein and extensive homology to human erythrocyte glutathione reductase and mercuric reductase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3693355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Pons, G., Raefsky-Estrin, C., Carothers, D. J., Pepin, R. A., Javed, A. A., Jesse, B. W., Ganapathi, M. K., Samols, D., Patel, M. S. <strong>Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human alpha-ketoacid dehydrogenase complexes.</strong> Proc. Nat. Acad. Sci. 85: 1422-1426, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3278312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3278312</a>] [<a href="https://doi.org/10.1073/pnas.85.5.1422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3278312">Pons et al. (1988)</a> isolated cDNA clones comprising the entire coding region for dihydrolipoamide dehydrogenase from a human liver cDNA library. The sequence encodes a deduced 509-amino acid precursor protein. The mature E3 enzyme is a homodimer, and each subunit has a molecular mass of about 50 kD. Blot hybridization analysis detected 2 mRNA transcripts, 2.2 and 2.4-kb, in human tissues and fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3278312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Using somatic cell hybrids, <a href="#18" class="mim-tip-reference" title="Otulakowski, G., Robinson, B. H., Willard, H. F. <strong>Gene for lipoamide dehydrogenase maps to human chromosome 7.</strong> Somat. Cell Molec. Genet. 14: 411-414, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3399966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3399966</a>] [<a href="https://doi.org/10.1007/BF01534650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3399966">Otulakowski et al. (1988)</a> assigned the gene for lipoamide dehydrogenase to chromosome 7. <a href="#16" class="mim-tip-reference" title="Olson, S., Song, B. J., Huh, T.-L., Chi, Y.-T., Veech, R. L., McBride, O. W. <strong>Three genes for enzymes of the pyruvate dehydrogenase complex map to human chromosomes 3, 7, and X.</strong> Am. J. Hum. Genet. 46: 340-349, 1990. Note: Erratum: Am. J. Hum. Genet. 46: 1235 only, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967901</a>]" pmid="1967901">Olson et al. (1990)</a> confirmed the assignment of the E3 gene to chromosome 7. <a href="#23" class="mim-tip-reference" title="Scherer, S. W., Otulakowski, G., Robinson, B. H., Tsui, L.-C. <strong>Localization of the human dihydrolipoamide dehydrogenase gene (DLD) to 7q31-q32.</strong> Cytogenet. Cell Genet. 56: 176-177, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2055113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2055113</a>] [<a href="https://doi.org/10.1159/000133081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2055113">Scherer et al. (1991)</a> refined the localization to 7q31-q32. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1967901+3399966+2055113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By interspecies backcross analysis, <a href="#13" class="mim-tip-reference" title="Johnson, M., Yang, H.-S., Johanning, G. L., Patel, M. S. <strong>Characterization of the mouse dihydrolipoamide dehydrogenase (Dld) gene: genomic structure, promoter sequence, and chromosomal localization.</strong> Genomics 41: 320-326, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9169128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9169128</a>] [<a href="https://doi.org/10.1006/geno.1997.4670" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9169128">Johnson et al. (1997)</a> mapped the mouse Dld gene to the proximal region of chromosome 12, a region that shows homology of synteny with human 7q31-q32. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9169128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Feigenbaum, A. S., Robinson, B. H. <strong>The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements.</strong> Genomics 17: 376-381, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8406489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8406489</a>] [<a href="https://doi.org/10.1006/geno.1993.1335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8406489">Feigenbaum and Robinson (1993)</a> determined that the DLD gene contains 14 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8406489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The mitochondrial glycine cleavage system (GCS; <a href="https://enzyme.expasy.org/EC/2.1.2.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.1.2.10</a>) is a multienzyme system comprising 4 components referred to as P (<a href="/entry/238300">238300</a>), H (<a href="/entry/238330">238330</a>), T (<a href="/entry/238310">238310</a>), and L proteins. L protein represents dihydrolipoamide dehydrogenase, a housekeeping enzyme that serves as a component of other complex enzyme systems such as the pyruvate dehydrogenase complex (see <a href="/entry/300502">300502</a>) and the branched chain ketoacid dehydrogenase complex (see <a href="/entry/608348">608348</a>) (<a href="#22" class="mim-tip-reference" title="Sakata, Y., Owada, Y., Sato, K., Kojima, K., Hisanaga, K., Shinka, T., Suzuki, Y., Aoki, Y., Satoh, J., Kondo, H., Matsubara, Y., Kure, S. <strong>Structure and expression of the glycine cleavage system in rat central nervous system.</strong> Molec. Brain Res. 94: 119-130, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11597772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11597772</a>] [<a href="https://doi.org/10.1016/s0169-328x(01)00225-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11597772">Sakata et al., 2001</a>). No defect in the L protein has been identified as the cause of glycine encephalopathy (<a href="/entry/605899">605899</a>); see review of <a href="#10" class="mim-tip-reference" title="Hamosh, A., Johnston, M. V. <strong>Nonketotic hyperglycinemia. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001. Pp. 2065-2078."None>Hamosh and Johnston (2001)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11597772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Petrat, F., Paluch, S., Dogruoz, E., Dorfler, P., Kirsch, M., Korth, H.-G., Sustmann, R., de Groot, H. <strong>Reduction of Fe(III) ions complexed to physiological ligands by lipoyl dehydrogenase and other flavoenzymes in vitro: implications for an enzymatic reduction of Fe(III) ions of the labile iron pool.</strong> J. Biol. Chem. 278: 46403-46413, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12963736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12963736</a>] [<a href="https://doi.org/10.1074/jbc.M305291200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12963736">Petrat et al. (2003)</a> found that DLD catalyzes the one-electron reduction of Fe3+ complexes of citrate, ATP, and ADP from NAD(P)H, indicating a role for the enzyme in intracellular metabolism of the labile iron pool. The findings had implications for the fate of iron in transit, which has a substantial cytotoxic potential via iron-dependent generation of reactive oxygen species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12963736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Babady, N. E., Pang, Y.-P., Elpeleg, O., Isaya, G. <strong>Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.</strong> Proc. Nat. Acad. Sci. 104: 6158-6163, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17404228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17404228</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17404228[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.0610618104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17404228">Babady et al. (2007)</a> found that destabilization of the DLD homodimer to a monomer enabled the enzyme to function as a serine protease. A catalytic dyad (S456-E431) buried at the homodimer interface was identified. Mutations at the 456 or 431 residues abolished the proteolytic activity. Proteolytically active DLD removed a functional critical domain from the N terminus of frataxin (FXN; <a href="/entry/606829">606829</a>), a mitochondrial protein involved in iron metabolism and antioxidant protection. Mutation in FXN causes the neurodegenerative and cardiac disease Friedreich ataxia (FRDA; <a href="/entry/229300">229300</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17404228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>During enzymatic activity, DLD oxidizes dihydrolipoic moieties and generates NADH from NAD+ in a forward reaction, whereas it reduces model substrates like lipoic acid or lipoamide and oxidizes NADH to NAD+ in a reverse reaction. If the NAD+ or lipoic acid electron-acceptor substrate is scarce, O2 can be reduced to a superoxide anion and then dismutated to H2O2, generating reactive oxygen species (ROS). DLD thus acts as a diaphorase, reducing various organic molecules via the transfer of a single electron. Monomerization of DLD is thought to transform its activity to a diaphorase (summary by <a href="#1" class="mim-tip-reference" title="Ambrus, A., Torocsik, B., Tretter, L., Ozohanics, O., Adam-Vizi, V. <strong>Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase.</strong> Hum. Molec. Genet. 20: 2984-2995, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21558426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21558426</a>] [<a href="https://doi.org/10.1093/hmg/ddr202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21558426">Ambrus et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21558426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>) reported by <a href="#21" class="mim-tip-reference" title="Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T. <strong>Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.</strong> Europ. J. Pediat. 145: 271-274, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3769994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3769994</a>] [<a href="https://doi.org/10.1007/BF00439399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3769994">Sakaguchi et al. (1986)</a>, <a href="#14" class="mim-tip-reference" title="Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S. <strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong> Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8506365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8506365</a>] [<a href="https://doi.org/10.1073/pnas.90.11.5186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8506365">Liu et al. (1993)</a> demonstrated compound heterozygosity for missense mutations in the DLD gene (<a href="#0001">238331.0001</a> and <a href="#0002">238331.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3769994+8506365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 13 affected patients from 7 Ashkenazi Jewish families with LAD deficiency, <a href="#24" class="mim-tip-reference" title="Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N. <strong>Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.</strong> Am. J. Med. Genet. 82: 177-182, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9934985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9934985</a>]" pmid="9934985">Shaag et al. (1999)</a> identified a mutation (G229C; <a href="#0006">238331.0006</a>) in the DLD gene in 12 of 14 mutated alleles. The other 2 alleles had a previously identified insertion mutation (<a href="#0003">238331.0003</a>). Homozygosity for the G229C mutation was associated with a relatively milder phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9934985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with E3 deficiency who developed clinical characteristics of Leigh syndrome (<a href="/entry/256000">256000</a>), <a href="#9" class="mim-tip-reference" title="Grafakou, O., Oexle, K., van den Heuvel, L., Smeets, R., Trijbels, F., Goebel, H. H., Bosshard, N., Superti-Furga, A., Steinmann, B., Smeitink, J. <strong>Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations: description of the first E3 splice site mutation.</strong> Europ. J. Pediat. 162: 714-718, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925875</a>] [<a href="https://doi.org/10.1007/s00431-003-1282-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12925875">Grafakou et al. (2003)</a> identified heterozygosity for 2 novel mutations in the DLD gene (<a href="#0007">238331.0007</a> and <a href="#0008">238331.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12925875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Babady, N. E., Pang, Y.-P., Elpeleg, O., Isaya, G. <strong>Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.</strong> Proc. Nat. Acad. Sci. 104: 6158-6163, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17404228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17404228</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17404228[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.0610618104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17404228">Babady et al. (2007)</a> found that some DLD mutations at the homodimer interface domain enhanced serine proteolytic activity, while also causing partial or complete loss of DLD activity. The findings indicated a mechanism by which certain DLD mutations could induce the loss of a primary metabolic activity and the gain of a proteolytic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17404228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional analysis of DLD mutations purified in E. coli, <a href="#1" class="mim-tip-reference" title="Ambrus, A., Torocsik, B., Tretter, L., Ozohanics, O., Adam-Vizi, V. <strong>Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase.</strong> Hum. Molec. Genet. 20: 2984-2995, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21558426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21558426</a>] [<a href="https://doi.org/10.1093/hmg/ddr202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21558426">Ambrus et al. (2011)</a> found that the D479V (<a href="#0011">238331.0011</a>), E375K (<a href="#0009">238331.0009</a>), P488L (<a href="#0002">238331.0002</a>), and G194C (<a href="#0006">238331.0006</a>) mutations significantly increased the rate of generation of reactive oxygen species compared to controls and to other mutations (e.g., K72E, <a href="#0001">238331.0001</a>). These 4 mutants also showed increased sensitivity of ROS generation to an acidic shift in pH. There was no correlation between conformational change in the mutant proteins or monomerization and the ability to generate ROS. The findings suggested that the generation of ROS may also contribute to the disease in some cases, and that the use of antioxidants may be beneficial. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21558426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional analysis in E. coli, <a href="#27" class="mim-tip-reference" title="Vaubel, R. A., Rustin, P., Isaya, G. <strong>Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells.</strong> J. Biol. Chem. 286: 40232-40245, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21930696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21930696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21930696[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M111.274415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21930696">Vaubel et al. (2011)</a> found that all pathogenic DLD mutations caused variable degrees of decreased DLD activity. However, those at the dimer interface that were associated with severe multisystem disorders of infancy, including E375K, D479V, R48G (<a href="#0012">238331.0012</a>), and R460G, also enhanced proteolytic and/or diaphorase activity of DLD. Human DLD proteins carrying each individual mutation complemented the respiratory-deficient phenotype of yeast cells lacking endogenous DLD even when residual DLD activity was as low as 21% of controls. However, under elevated oxidative stress or with time, expression of DLD proteins with dimer interface mutations greatly accelerated the loss of respiratory function, resulting from enhanced oxidative damage to the lipoic acid cofactor of PDC and KGDC and other mitochondrial targets. This effect was not observed with the G194C mutation, which affects the NAD(+)-binding domain and is generally associated with a milder phenotype, or a mutation that disrupts the proteolytic active site of DLD. Lipoic acid cofactor was also damaged in human D479V-homozygous fibroblasts after exposure to oxidative stress. DLD mutations affecting the dimer interface also appeared to affect FXN turnover. <a href="#27" class="mim-tip-reference" title="Vaubel, R. A., Rustin, P., Isaya, G. <strong>Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells.</strong> J. Biol. Chem. 286: 40232-40245, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21930696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21930696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21930696[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M111.274415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21930696">Vaubel et al. (2011)</a> concluded that the cryptic activities of DLD can promote oxidative damage and may thus contribute to the variable clinical severity of DLD mutations in addition to mutational effects on enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21930696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>13 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/238331" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=238331[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, LYS72GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121964987 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964987;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012742" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012742" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012742</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>) reported by <a href="#21" class="mim-tip-reference" title="Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T. <strong>Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.</strong> Europ. J. Pediat. 145: 271-274, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3769994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3769994</a>] [<a href="https://doi.org/10.1007/BF00439399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3769994">Sakaguchi et al. (1986)</a>, <a href="#14" class="mim-tip-reference" title="Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S. <strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong> Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8506365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8506365</a>] [<a href="https://doi.org/10.1073/pnas.90.11.5186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8506365">Liu et al. (1993)</a> demonstrated compound heterozygosity for missense mutations in the DLD gene: an A-G change, resulting in a lys72-to-glu (K72E) substitution (K37E in the processed protein, <a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>), and a C-T change, resulting in a pro488-to-leu (P488L; <a href="#0002">238331.0002</a>) substitution (P453L in the processed protein, <a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>). These mutations altered the active site and possibly the binding of FAD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3769994+8506365+15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional expression studies, <a href="#1" class="mim-tip-reference" title="Ambrus, A., Torocsik, B., Tretter, L., Ozohanics, O., Adam-Vizi, V. <strong>Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase.</strong> Hum. Molec. Genet. 20: 2984-2995, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21558426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21558426</a>] [<a href="https://doi.org/10.1093/hmg/ddr202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21558426">Ambrus et al. (2011)</a> found that the P453L mutation resulted in a significant decrease in LADH activity as well as a significant increase in the generation of reactive oxygen species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21558426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, PRO488LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121964988 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964988;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121964988?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012743" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012743" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012743</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro488-to-leu (P488L) mutation in the DLD gene that was found in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>) by <a href="#14" class="mim-tip-reference" title="Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S. <strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong> Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8506365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8506365</a>] [<a href="https://doi.org/10.1073/pnas.90.11.5186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8506365">Liu et al. (1993)</a>, see <a href="#0001">238331.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8506365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, 1-BP INS, 105A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs753234219 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs753234219;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs753234219?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs753234219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs753234219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000409901 OR RCV001591045" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000409901, RCV001591045" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000409901...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), who was originally reported by <a href="#6" class="mim-tip-reference" title="Craigen, W. J. <strong>Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.</strong> Pediat. Neurol. 14: 69-71, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8652022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8652022</a>] [<a href="https://doi.org/10.1016/0887-8994(96)00005-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8652022">Craigen (1996)</a>, <a href="#11" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. <strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong> Hum. Molec. Genet. 5: 1925-1930, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968745</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968745">Hong et al. (1996)</a> identified compound heterozygosity for 2 mutations in the DLD gene: a 1-bp insertion (105insA) in the last codon of the leader sequence predicted to result in a frameshift and premature termination (Y35X), and an arg495-to-gly (R495G; <a href="#0004">238331.0004</a>) substitution (R460G in the processed protein, <a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>). The patient had developmental delay, hypotonia, metabolic acidosis (elevated serum lactate and pyruvate), a history of transient neonatal hypoglycemia, and features of Leigh syndrome; she died at age 28 months. Plasma amino acid analysis in the patient initially showed increased leucine, isoleucine, and valine. Urine organic acid analysis showed mild to moderate increases of lactic, 2-hydroxybutyric, 3-hydroxybutyric, alpha-ketoglutaric, and 3-hydroxyisovaleric acids. She died at age 28 months. Activities of the PDC and E3 in patient lymphocytes were 26% and 2% of control values, respectively, and in patient fibroblasts were 11% and 14%, respectively. KGDC activity in fibroblasts was 20%. Corresponding values in the clinically unaffected parents were about 50% of normal, except for KGDC, which was normal. These findings suggested that a partial reduction in E3 is not rate-limiting for KGDC activity in fibroblasts. Glycine was also not increased in the patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8652022+15712224+8968745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 patients of Ashkenazi-Jewish origin with DLDD, <a href="#7" class="mim-tip-reference" title="Elpeleg, O. N., Shaag, A., Glustein, J. Z., Anikster, Y., Joseph, A., Saada, A. <strong>Lipoamide dehydrogenase deficiency in Ashkenazi Jews: an insertion mutation in the mitochondrial leader sequence.</strong> Hum. Mutat. 10: 256-257, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298831</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<256::AID-HUMU16>3.0.CO;2-Z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9298831">Elpeleg et al. (1997)</a> identified the 105insA mutation in the DLD gene. The 2 patients were heterozygotes for the mutation; no other mutation was identified in the coding region. Heterozygosity for the 105insA mutation was also identified in the cDNA of the father and 1 brother of patient 1, and in the mother and 1 sister of patient 2. Because the enzymatic activity of lipoamide dehydrogenase in muscle tissue of both patients was reduced to 8 to 20% of the control mean, <a href="#7" class="mim-tip-reference" title="Elpeleg, O. N., Shaag, A., Glustein, J. Z., Anikster, Y., Joseph, A., Saada, A. <strong>Lipoamide dehydrogenase deficiency in Ashkenazi Jews: an insertion mutation in the mitochondrial leader sequence.</strong> Hum. Mutat. 10: 256-257, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298831</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<256::AID-HUMU16>3.0.CO;2-Z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9298831">Elpeleg et al. (1997)</a> presumed that both patients were compound heterozygotes for this and another unidentified mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, ARG495GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121964989 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964989;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012746" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012746" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012746</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg495-to-gly (R495G) mutation in the DLD gene that was found in compound heterozygous state in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>) by <a href="#11" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. <strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong> Hum. Molec. Genet. 5: 1925-1930, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968745</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968745">Hong et al. (1996)</a>, see <a href="#0003">238331.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, GLY229CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121964990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964990;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121964990?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012744 OR RCV000185853 OR RCV000624277 OR RCV004528103" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012744, RCV000185853, RCV000624277, RCV004528103" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012744...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a series of 7 Ashkenazi Jewish families with dihydrolipoyl dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), <a href="#24" class="mim-tip-reference" title="Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N. <strong>Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.</strong> Am. J. Med. Genet. 82: 177-182, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9934985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9934985</a>]" pmid="9934985">Shaag et al. (1999)</a> identified a mutation in the DLD gene resulting in a gly229-to-cys (G229C) substitution at a highly conserved residue in the NAD(+)-binding domain. The G229C mutation accounted for 12 of 14 mutant alleles. G229C corresponds to G194C in the mature protein (<a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>). In a sample of 845 anonymous individuals of Ashkenazi Jewish origin, 9 heterozygotes for the G194C mutation were identified, yielding a carrier rate of 1:94. The other 2 alleles in the series had a previously identified insertion mutation (<a href="#0003">238331.0003</a>). The disease course and age at onset were highly variable. Some patients had few neurologic sequelae and long survival. Two patients presented immediately after birth, 9 around age 2 years, and 2 as adults. All had recurrent episodes of vomiting, abdominal pain, and hepatomegaly, usually associated with neurologic signs during the episodes. Episodes were associated with lactic acidosis, abnormal liver enzymes, and prolonged prothrombin time. Biochemical anomalies, such as increased branched-chain amino acids and increased alpha-ketoacids were not commonly found. The 2 patients who presented neonatally had residual neurologic damage with attention deficit-hyperactivity disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or as adults suffered from exertional fatigue between episodes of decompensation but were otherwise asymptomatic and showed normal psychomotor development. Two patients died because of intractable metabolic acidosis and multiorgan failure. In all patients, E3 activity was reduced to 8 to 21% of the control value in muscle or lymphocytes. In 4 patients tested, the E3 protein in muscle was reduced to 20 to 60% of control. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9934985+15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#12" class="mim-tip-reference" title="Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S. <strong>Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.</strong> J. Inherit. Metab. Dis. 26: 816-818, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14765544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14765544</a>] [<a href="https://doi.org/10.1023/b:boli.0000010004.12053.5b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14765544">Hong et al. (2003)</a> reported 2 sibs, born of consanguineous Palestinian Arab Muslim parents, with E3 deficiency due to homozygosity for the G194C mutation. A girl died in infancy during an episode of repeated vomiting associated with encephalopathy. Two previous sibs had died under similar circumstances. A brother had recurrent episodes of vomiting associated with encephalopathy from age 8 months. Examination at age 10 years showed generalized muscle weakness and wasting, ataxic gait, hepatomegaly, and lactic acidemia. He was treated with riboflavin, coenzyme Q, biotin, and carnitine. Six years later, he was functioning well at a normal school, but had slight ataxia and intention tremor. Two additional patients, both of Ashkenazi Jewish descent, had a severe form of E3 deficiency and the G194C mutation. One had repeated episodes of hypoglycemia and was in a persistent vegetative state at age 4 years; he died soon after. A girl had recurrent episodes of repeated vomiting and acidosis since infancy; she died of hepatic failure at age 5 years. All patients had decreased levels of the E3 protein (range, 35-68% of controls) and decreased E3 activity (8-33% of controls). <a href="#12" class="mim-tip-reference" title="Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S. <strong>Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.</strong> J. Inherit. Metab. Dis. 26: 816-818, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14765544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14765544</a>] [<a href="https://doi.org/10.1023/b:boli.0000010004.12053.5b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14765544">Hong et al. (2003)</a> emphasized the favorable outcome in the 1 child treated with riboflavin and additional supplements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14765544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional expression studies, <a href="#1" class="mim-tip-reference" title="Ambrus, A., Torocsik, B., Tretter, L., Ozohanics, O., Adam-Vizi, V. <strong>Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase.</strong> Hum. Molec. Genet. 20: 2984-2995, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21558426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21558426</a>] [<a href="https://doi.org/10.1093/hmg/ddr202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21558426">Ambrus et al. (2011)</a> found that the G194C mutant protein caused no significant changes in LADH activity but did result in significantly increased generation of reactive oxygen species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21558426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, ILE393THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121964991 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964991;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012747" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012747" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012747</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), <a href="#9" class="mim-tip-reference" title="Grafakou, O., Oexle, K., van den Heuvel, L., Smeets, R., Trijbels, F., Goebel, H. H., Bosshard, N., Superti-Furga, A., Steinmann, B., Smeitink, J. <strong>Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations: description of the first E3 splice site mutation.</strong> Europ. J. Pediat. 162: 714-718, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925875</a>] [<a href="https://doi.org/10.1007/s00431-003-1282-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12925875">Grafakou et al. (2003)</a> identified heterozygosity for 2 mutations in the DLD gene: an ile393-to-thr (I393T) substitution in exon 11, postulated to interfere with protein dimerization, and an IVS9+1G-A change at a consensus splice site (<a href="#0008">238331.0008</a>). I393T corresponds to I358T in the mature protein (<a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>). The I358T mutation cosegregated with a polymorphism, 1422A-C, in exon 13; both appeared to be homozygous in cDNA studies, suggesting that the mRNA product of the splice site mutation was unstable. One year after presentation, the patient developed a stroke-like episode, and brain MRI showed symmetric hyperintensity consistent with Leigh syndrome (<a href="/entry/256000">256000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12925875+15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, IVS9DS, G-A, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1328820332 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1328820332;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1328820332?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1328820332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1328820332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012749" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012749" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012749</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the splice site mutation in the DLD gene (IVS9+1G-A) that was found in compound heterozygous state in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>) by <a href="#9" class="mim-tip-reference" title="Grafakou, O., Oexle, K., van den Heuvel, L., Smeets, R., Trijbels, F., Goebel, H. H., Bosshard, N., Superti-Furga, A., Steinmann, B., Smeitink, J. <strong>Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations: description of the first E3 splice site mutation.</strong> Europ. J. Pediat. 162: 714-718, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925875</a>] [<a href="https://doi.org/10.1007/s00431-003-1282-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12925875">Grafakou et al. (2003)</a>, see <a href="#0007">238331.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12925875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, GLU375LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121964992 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964992;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121964992?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012751 OR RCV000185859 OR RCV001266054 OR RCV002251899 OR RCV004528104" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012751, RCV000185859, RCV001266054, RCV002251899, RCV004528104" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012751...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-week-old boy with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), <a href="#5" class="mim-tip-reference" title="Cerna, L., Wenchich, L., Hansikova, H., Kmoch, S., Peskova, K., Chrastina, P., Brynda, J., Zeman, J. <strong>Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.</strong> Med. Sci. Monit. 7: 1319-1325, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687750</a>]" pmid="11687750">Cerna et al. (2001)</a> identified compound heterozygosity for 2 mutations in the DLD gene: a 1123G-A transition resulting in a glu375-to-lys (E375K) substitution and a 1081A-G transition resulting in a met361-to-val (M361V; <a href="#0010">238331.0010</a>) substitution. E375K and M361V correspond to E340K and M326V in the mature protein, respectively (<a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>). DLD activity in the patient's lymphocytes, muscle mitochondria, and fibroblasts was less than 5% of control values, and Western blot analysis showed a decrease in DLD protein levels to 40% of controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11687750+15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#4" class="mim-tip-reference" title="Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H. <strong>Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.</strong> Am. J. Med. Genet. 140A: 1542-1552, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770810</a>] [<a href="https://doi.org/10.1002/ajmg.a.31313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16770810">Cameron et al. (2006)</a> noted that the E375K mutation occurs at a conserved residue in the central domain of DLD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, MET361VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121964993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964993;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121964993?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121964993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121964993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012752" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012752" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012752</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the met361-to-val (M361V) mutation in the DLD gene that was found in compound heterozygous state in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>) by <a href="#5" class="mim-tip-reference" title="Cerna, L., Wenchich, L., Hansikova, H., Kmoch, S., Peskova, K., Chrastina, P., Brynda, J., Zeman, J. <strong>Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.</strong> Med. Sci. Monit. 7: 1319-1325, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687750</a>]" pmid="11687750">Cerna et al. (2001)</a>, see <a href="#0009">238331.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, ASP479VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514649 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514649;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033216" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033216" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033216</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-month-old girl of Muslim origin with a severe neurodegenerative form of dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), <a href="#25" class="mim-tip-reference" title="Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N. <strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong> Biochem. Biophys. Res. Commun. 262: 163-166, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448086</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10448086">Shany et al. (1999)</a> identified a homozygous 1436A-T transversion in the DLD gene, resulting in an asp479-to-val (D479V) substitution, which is a D444V change in the processed protein (<a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al., 2005</a>). The substitution occurs in the interface domain of the DLD dimer, which was postulated to perturb the stability of the homodimer. The patient reported by <a href="#25" class="mim-tip-reference" title="Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N. <strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong> Biochem. Biophys. Res. Commun. 262: 163-166, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448086</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10448086">Shany et al. (1999)</a> presented on the third day of life with apathy, poor feeding, and lethargy. Laboratory studies showed hypoglycemia and severe lactic acidosis, but normal levels of branched-chain keto acids and alpha-ketoglutarate. Muscle biopsy showed no activity of the pyruvate dehydrogenase complex, severely decreased activity of the alpha-ketoglutarate dehydrogenase complex (2%), and decreased DLD activity at 15% of controls. Each of her unaffected parents had about 50% reduced DLD protein activity. She had recurrent episodes of metabolic acidosis, often triggered by infection. Clinical features included microcephaly, lack of psychomotor development, blindness, deafness, hypotonia, brisk reflexes, and mild hypertrophic cardiomyopathy. <a href="#25" class="mim-tip-reference" title="Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N. <strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong> Biochem. Biophys. Res. Commun. 262: 163-166, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448086</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10448086">Shany et al. (1999)</a> noted that the phenotypic severity in this patient was not correlated with residual DLD protein activity, since the G229C mutation (<a href="#0006">238331.0006</a>) was associated with even less activity (7%), but a milder phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10448086+15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Babady, N. E., Pang, Y.-P., Elpeleg, O., Isaya, G. <strong>Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.</strong> Proc. Nat. Acad. Sci. 104: 6158-6163, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17404228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17404228</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17404228[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.0610618104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17404228">Babady et al. (2007)</a> found that the D444V mutant protein had increased proteolytic activity compared to wildtype and that this proteolytic activity correlated with the monomer fraction of the mutant DLD protein. The appearance of this proteolytic activity may have contributed to the phenotypic severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17404228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, ARG482GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514650;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033217</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Algerian sibs, born of consanguineous parents, with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), <a href="#15" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. <strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong> Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>] [<a href="https://doi.org/10.1002/humu.9319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15712224">Odievre et al. (2005)</a> identified a homozygous 1444A-G transition in exon 13 of the DLD gene, resulting in an arg482-to-gly (R482G) substitution (R447G in the processed protein) in the dimer interface domain. The patients had originally been reported by <a href="#3" class="mim-tip-reference" title="Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A. <strong>Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.</strong> J. Pediat. 121: 255-258, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1640293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1640293</a>] [<a href="https://doi.org/10.1016/s0022-3476(05)81199-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1640293">Bonnefont et al. (1992)</a> as having alpha-ketoglutarate dehydrogenase deficiency. They had a severe form of the disorder, resulting in death in all by age 30 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1640293+15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DLD, ILE47THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514651;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033218" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033218" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033218</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 second-cousin Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase deficiency (DLDD; <a href="/entry/246900">246900</a>), <a href="#4" class="mim-tip-reference" title="Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H. <strong>Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.</strong> Am. J. Med. Genet. 140A: 1542-1552, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770810</a>] [<a href="https://doi.org/10.1002/ajmg.a.31313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16770810">Cameron et al. (2006)</a> identified compound heterozygosity for 2 mutations in the DLD gene. Both patients carried a heterozygous T-to-C transition in exon 3, resulting in an ile47-to-thr (I47T) substitution at a highly conserved region in the FAD functional domain. One patient had G229C (<a href="#0006">238331.0006</a>) on the other allele, and the other had E375K (<a href="#0009">238331.0009</a>) on the other allele. All unaffected parents were heterozygous for 1 of the mutations. Both patients had decreased activities of the KGDH (25% and 44%, respectively) and BCKDH (58% and 62%, respectively) complexes, but PDH complex activity was at the low end of normal (69% and 59%, respectively). DLD activity was decreased in both patients. The patient with the G229C mutation had a milder phenotype compared to the patient without that mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Steiert1990" class="mim-tip-reference" title="Steiert, P. S., Stauffer, L. T., Stauffer, G. V. <strong>The lpd gene product functions as the L protein in the Escherichia coli glycine cleavage enzyme system.</strong> J. Bacteriol. 172: 6142-6144, 1990.">Steiert et al. (1990)</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="Ambrus2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ambrus, A., Torocsik, B., Tretter, L., Ozohanics, O., Adam-Vizi, V.
|
|
<strong>Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase.</strong>
|
|
Hum. Molec. Genet. 20: 2984-2995, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21558426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21558426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21558426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddr202" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Babady2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Babady, N. E., Pang, Y.-P., Elpeleg, O., Isaya, G.
|
|
<strong>Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 6158-6163, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17404228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17404228</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17404228[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=17404228" target="_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.0610618104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bonnefont1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A.
|
|
<strong>Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.</strong>
|
|
J. Pediat. 121: 255-258, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1640293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1640293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1640293" target="_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(05)81199-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cameron2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H.
|
|
<strong>Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.</strong>
|
|
Am. J. Med. Genet. 140A: 1542-1552, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770810" target="_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.31313" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Cerna2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cerna, L., Wenchich, L., Hansikova, H., Kmoch, S., Peskova, K., Chrastina, P., Brynda, J., Zeman, J.
|
|
<strong>Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.</strong>
|
|
Med. Sci. Monit. 7: 1319-1325, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687750" 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="6" class="mim-anchor"></a>
|
|
<a id="Craigen1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Craigen, W. J.
|
|
<strong>Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.</strong>
|
|
Pediat. Neurol. 14: 69-71, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8652022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8652022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8652022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0887-8994(96)00005-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Elpeleg1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elpeleg, O. N., Shaag, A., Glustein, J. Z., Anikster, Y., Joseph, A., Saada, A.
|
|
<strong>Lipoamide dehydrogenase deficiency in Ashkenazi Jews: an insertion mutation in the mitochondrial leader sequence.</strong>
|
|
Hum. Mutat. 10: 256-257, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298831" target="_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)1098-1004(1997)10:3<256::AID-HUMU16>3.0.CO;2-Z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Feigenbaum1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Feigenbaum, A. S., Robinson, B. H.
|
|
<strong>The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements.</strong>
|
|
Genomics 17: 376-381, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8406489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8406489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8406489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1993.1335" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Grafakou2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grafakou, O., Oexle, K., van den Heuvel, L., Smeets, R., Trijbels, F., Goebel, H. H., Bosshard, N., Superti-Furga, A., Steinmann, B., Smeitink, J.
|
|
<strong>Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations: description of the first E3 splice site mutation.</strong>
|
|
Europ. J. Pediat. 162: 714-718, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925875</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12925875" target="_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/s00431-003-1282-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Hamosh2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamosh, A., Johnston, M. V.
|
|
<strong>Nonketotic hyperglycinemia. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001. Pp. 2065-2078.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Hong1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S.
|
|
<strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong>
|
|
Hum. Molec. Genet. 5: 1925-1930, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.12.1925" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Hong2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S.
|
|
<strong>Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.</strong>
|
|
J. Inherit. Metab. Dis. 26: 816-818, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14765544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14765544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14765544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1023/b:boli.0000010004.12053.5b" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Johnson1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnson, M., Yang, H.-S., Johanning, G. L., Patel, M. S.
|
|
<strong>Characterization of the mouse dihydrolipoamide dehydrogenase (Dld) gene: genomic structure, promoter sequence, and chromosomal localization.</strong>
|
|
Genomics 41: 320-326, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9169128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9169128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9169128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1997.4670" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Liu1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S.
|
|
<strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8506365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8506365</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8506365" target="_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.90.11.5186" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Odievre2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P.
|
|
<strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong>
|
|
Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15712224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.9319" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Olson1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Olson, S., Song, B. J., Huh, T.-L., Chi, Y.-T., Veech, R. L., McBride, O. W.
|
|
<strong>Three genes for enzymes of the pyruvate dehydrogenase complex map to human chromosomes 3, 7, and X.</strong>
|
|
Am. J. Hum. Genet. 46: 340-349, 1990. Note: Erratum: Am. J. Hum. Genet. 46: 1235 only, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967901</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1967901" 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="17" class="mim-anchor"></a>
|
|
<a id="Otulakowski1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otulakowski, G., Robinson, B. H.
|
|
<strong>Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase.</strong>
|
|
J. Biol. Chem. 262: 17313-17318, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3693355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3693355</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3693355" 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="18" class="mim-anchor"></a>
|
|
<a id="Otulakowski1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otulakowski, G., Robinson, B. H., Willard, H. F.
|
|
<strong>Gene for lipoamide dehydrogenase maps to human chromosome 7.</strong>
|
|
Somat. Cell Molec. Genet. 14: 411-414, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3399966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3399966</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3399966" target="_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/BF01534650" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Petrat2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Petrat, F., Paluch, S., Dogruoz, E., Dorfler, P., Kirsch, M., Korth, H.-G., Sustmann, R., de Groot, H.
|
|
<strong>Reduction of Fe(III) ions complexed to physiological ligands by lipoyl dehydrogenase and other flavoenzymes in vitro: implications for an enzymatic reduction of Fe(III) ions of the labile iron pool.</strong>
|
|
J. Biol. Chem. 278: 46403-46413, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12963736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12963736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12963736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M305291200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Pons1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pons, G., Raefsky-Estrin, C., Carothers, D. J., Pepin, R. A., Javed, A. A., Jesse, B. W., Ganapathi, M. K., Samols, D., Patel, M. S.
|
|
<strong>Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human alpha-ketoacid dehydrogenase complexes.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 1422-1426, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3278312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3278312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3278312" target="_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.85.5.1422" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Sakaguchi1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T.
|
|
<strong>Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.</strong>
|
|
Europ. J. Pediat. 145: 271-274, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3769994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3769994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3769994" target="_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/BF00439399" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Sakata2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sakata, Y., Owada, Y., Sato, K., Kojima, K., Hisanaga, K., Shinka, T., Suzuki, Y., Aoki, Y., Satoh, J., Kondo, H., Matsubara, Y., Kure, S.
|
|
<strong>Structure and expression of the glycine cleavage system in rat central nervous system.</strong>
|
|
Molec. Brain Res. 94: 119-130, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11597772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11597772</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11597772" target="_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/s0169-328x(01)00225-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Scherer1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scherer, S. W., Otulakowski, G., Robinson, B. H., Tsui, L.-C.
|
|
<strong>Localization of the human dihydrolipoamide dehydrogenase gene (DLD) to 7q31-q32.</strong>
|
|
Cytogenet. Cell Genet. 56: 176-177, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2055113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2055113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2055113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000133081" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Shaag1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N.
|
|
<strong>Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.</strong>
|
|
Am. J. Med. Genet. 82: 177-182, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9934985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9934985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9934985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Shany1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N.
|
|
<strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong>
|
|
Biochem. Biophys. Res. Commun. 262: 163-166, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10448086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1999.1133" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Steiert1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Steiert, P. S., Stauffer, L. T., Stauffer, G. V.
|
|
<strong>The lpd gene product functions as the L protein in the Escherichia coli glycine cleavage enzyme system.</strong>
|
|
J. Bacteriol. 172: 6142-6144, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2211531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2211531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2211531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/jb.172.10.6142-6144.1990" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Vaubel2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vaubel, R. A., Rustin, P., Isaya, G.
|
|
<strong>Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells.</strong>
|
|
J. Biol. Chem. 286: 40232-40245, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21930696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21930696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21930696[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=21930696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M111.274415" 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">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 2/28/2013
|
|
</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 : 8/17/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/15/2016
|
|
</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 : 07/09/2016<br>carol : 9/1/2015<br>carol : 7/8/2015<br>mcolton : 7/7/2015<br>carol : 9/17/2013<br>terry : 3/28/2013<br>carol : 3/8/2013<br>carol : 3/5/2013<br>ckniffin : 2/28/2013<br>alopez : 6/13/2005<br>carol : 6/22/2001<br>carol : 5/17/2001<br>carol : 5/2/2001<br>carol : 5/2/2001<br>dkim : 11/13/1998<br>carol : 7/16/1998<br>joanna : 1/23/1997<br>mimadm : 3/11/1994<br>carol : 8/17/1992
|
|
</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> 238331
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
DIHYDROLIPOAMIDE DEHYDROGENASE; DLD
|
|
|
|
</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">
|
|
PYRUVATE DEHYDROGENASE COMPONENT E3; PHE3; E3<br />
|
|
BRANCHED CHAIN ALPHA-KETO ACID DEHYDROGENASE COMPLEX, E3 COMPONENT<br />
|
|
LIPOAMIDE REDUCTASE<br />
|
|
LIPOAMIDE DEHYDROGENASE; LAD; LADH<br />
|
|
LIPOYL DEHYDROGENASE<br />
|
|
DIHYDROLIPOYL DEHYDROGENASE<br />
|
|
DIAPHORASE<br />
|
|
GLYCINE CLEAVAGE SYSTEM L PROTEIN; GCSL
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: DLD</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 124184009, 767497003;
|
|
|
|
|
|
<strong>ICD10CM:</strong> D74.0;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 7q31.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 7:107,891,107-107,921,198 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
7q31.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Dihydrolipoamide dehydrogenase deficiency
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
246900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The DLD gene encodes dihydrolipoamide dehydrogenase (EC 1.8.1.4), a flavoprotein component known as E3 that is common to the 3 alpha-ketoacid dehydrogenase multienzyme complexes, namely, pyruvate dehydrogenase complex (PDC), the alpha-ketoglutarate dehydrogenase complex (KGDC), and the branched-chain alpha-keto acid dehydrogenase complex (BCKDC). The enzyme is a functional homodimer of the DLD protein and catalyzes the oxidative regeneration of a lipoic acid cofactor covalently bound to E2 (DBT; 248610) yielding NADH. The DLD enzyme is also a component, referred to as the L protein, of the mitochondrial glycine cleavage system (GCS; EC 2.1.2.10). In addition, DLD has cryptic activities as a diaphorase and a serine protease (summary by Hong et al., 1996 and Vaubel et al., 2011). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using a cDNA corresponding to lipoamide dehydrogenase isolated from a porcine adrenal medulla library, Otulakowski and Robinson (1987) isolated the corresponding human cDNA. The deduced amino acid sequence shows 96% identity to the porcine protein and extensive homology to human erythrocyte glutathione reductase and mercuric reductase. </p><p>Pons et al. (1988) isolated cDNA clones comprising the entire coding region for dihydrolipoamide dehydrogenase from a human liver cDNA library. The sequence encodes a deduced 509-amino acid precursor protein. The mature E3 enzyme is a homodimer, and each subunit has a molecular mass of about 50 kD. Blot hybridization analysis detected 2 mRNA transcripts, 2.2 and 2.4-kb, in human tissues and fibroblasts. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using somatic cell hybrids, Otulakowski et al. (1988) assigned the gene for lipoamide dehydrogenase to chromosome 7. Olson et al. (1990) confirmed the assignment of the E3 gene to chromosome 7. Scherer et al. (1991) refined the localization to 7q31-q32. </p><p>By interspecies backcross analysis, Johnson et al. (1997) mapped the mouse Dld gene to the proximal region of chromosome 12, a region that shows homology of synteny with human 7q31-q32. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Feigenbaum and Robinson (1993) determined that the DLD gene contains 14 exons. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The mitochondrial glycine cleavage system (GCS; EC 2.1.2.10) is a multienzyme system comprising 4 components referred to as P (238300), H (238330), T (238310), and L proteins. L protein represents dihydrolipoamide dehydrogenase, a housekeeping enzyme that serves as a component of other complex enzyme systems such as the pyruvate dehydrogenase complex (see 300502) and the branched chain ketoacid dehydrogenase complex (see 608348) (Sakata et al., 2001). No defect in the L protein has been identified as the cause of glycine encephalopathy (605899); see review of Hamosh and Johnston (2001). </p><p>Petrat et al. (2003) found that DLD catalyzes the one-electron reduction of Fe3+ complexes of citrate, ATP, and ADP from NAD(P)H, indicating a role for the enzyme in intracellular metabolism of the labile iron pool. The findings had implications for the fate of iron in transit, which has a substantial cytotoxic potential via iron-dependent generation of reactive oxygen species. </p><p>Babady et al. (2007) found that destabilization of the DLD homodimer to a monomer enabled the enzyme to function as a serine protease. A catalytic dyad (S456-E431) buried at the homodimer interface was identified. Mutations at the 456 or 431 residues abolished the proteolytic activity. Proteolytically active DLD removed a functional critical domain from the N terminus of frataxin (FXN; 606829), a mitochondrial protein involved in iron metabolism and antioxidant protection. Mutation in FXN causes the neurodegenerative and cardiac disease Friedreich ataxia (FRDA; 229300). </p><p>During enzymatic activity, DLD oxidizes dihydrolipoic moieties and generates NADH from NAD+ in a forward reaction, whereas it reduces model substrates like lipoic acid or lipoamide and oxidizes NADH to NAD+ in a reverse reaction. If the NAD+ or lipoic acid electron-acceptor substrate is scarce, O2 can be reduced to a superoxide anion and then dismutated to H2O2, generating reactive oxygen species (ROS). DLD thus acts as a diaphorase, reducing various organic molecules via the transfer of a single electron. Monomerization of DLD is thought to transform its activity to a diaphorase (summary by Ambrus et al., 2011). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900) reported by Sakaguchi et al. (1986), Liu et al. (1993) demonstrated compound heterozygosity for missense mutations in the DLD gene (238331.0001 and 238331.0002). </p><p>Among 13 affected patients from 7 Ashkenazi Jewish families with LAD deficiency, Shaag et al. (1999) identified a mutation (G229C; 238331.0006) in the DLD gene in 12 of 14 mutated alleles. The other 2 alleles had a previously identified insertion mutation (238331.0003). Homozygosity for the G229C mutation was associated with a relatively milder phenotype. </p><p>In a patient with E3 deficiency who developed clinical characteristics of Leigh syndrome (256000), Grafakou et al. (2003) identified heterozygosity for 2 novel mutations in the DLD gene (238331.0007 and 238331.0008). </p><p>Babady et al. (2007) found that some DLD mutations at the homodimer interface domain enhanced serine proteolytic activity, while also causing partial or complete loss of DLD activity. The findings indicated a mechanism by which certain DLD mutations could induce the loss of a primary metabolic activity and the gain of a proteolytic activity. </p><p>By in vitro functional analysis of DLD mutations purified in E. coli, Ambrus et al. (2011) found that the D479V (238331.0011), E375K (238331.0009), P488L (238331.0002), and G194C (238331.0006) mutations significantly increased the rate of generation of reactive oxygen species compared to controls and to other mutations (e.g., K72E, 238331.0001). These 4 mutants also showed increased sensitivity of ROS generation to an acidic shift in pH. There was no correlation between conformational change in the mutant proteins or monomerization and the ability to generate ROS. The findings suggested that the generation of ROS may also contribute to the disease in some cases, and that the use of antioxidants may be beneficial. </p><p>By in vitro functional analysis in E. coli, Vaubel et al. (2011) found that all pathogenic DLD mutations caused variable degrees of decreased DLD activity. However, those at the dimer interface that were associated with severe multisystem disorders of infancy, including E375K, D479V, R48G (238331.0012), and R460G, also enhanced proteolytic and/or diaphorase activity of DLD. Human DLD proteins carrying each individual mutation complemented the respiratory-deficient phenotype of yeast cells lacking endogenous DLD even when residual DLD activity was as low as 21% of controls. However, under elevated oxidative stress or with time, expression of DLD proteins with dimer interface mutations greatly accelerated the loss of respiratory function, resulting from enhanced oxidative damage to the lipoic acid cofactor of PDC and KGDC and other mitochondrial targets. This effect was not observed with the G194C mutation, which affects the NAD(+)-binding domain and is generally associated with a milder phenotype, or a mutation that disrupts the proteolytic active site of DLD. Lipoic acid cofactor was also damaged in human D479V-homozygous fibroblasts after exposure to oxidative stress. DLD mutations affecting the dimer interface also appeared to affect FXN turnover. Vaubel et al. (2011) concluded that the cryptic activities of DLD can promote oxidative damage and may thus contribute to the variable clinical severity of DLD mutations in addition to mutational effects on enzyme activity. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>13 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, LYS72GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964987,
|
|
|
|
|
|
|
|
ClinVar: RCV000012742
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900) reported by Sakaguchi et al. (1986), Liu et al. (1993) demonstrated compound heterozygosity for missense mutations in the DLD gene: an A-G change, resulting in a lys72-to-glu (K72E) substitution (K37E in the processed protein, Odievre et al., 2005), and a C-T change, resulting in a pro488-to-leu (P488L; 238331.0002) substitution (P453L in the processed protein, Odievre et al., 2005). These mutations altered the active site and possibly the binding of FAD. </p><p>By in vitro functional expression studies, Ambrus et al. (2011) found that the P453L mutation resulted in a significant decrease in LADH activity as well as a significant increase in the generation of reactive oxygen species. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, PRO488LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964988,
|
|
|
|
|
|
gnomAD: rs121964988,
|
|
|
|
|
|
ClinVar: RCV000012743
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro488-to-leu (P488L) mutation in the DLD gene that was found in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900) by Liu et al. (1993), see 238331.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, 1-BP INS, 105A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs753234219,
|
|
|
|
|
|
gnomAD: rs753234219,
|
|
|
|
|
|
ClinVar: RCV000409901, RCV001591045
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), who was originally reported by Craigen (1996), Hong et al. (1996) identified compound heterozygosity for 2 mutations in the DLD gene: a 1-bp insertion (105insA) in the last codon of the leader sequence predicted to result in a frameshift and premature termination (Y35X), and an arg495-to-gly (R495G; 238331.0004) substitution (R460G in the processed protein, Odievre et al., 2005). The patient had developmental delay, hypotonia, metabolic acidosis (elevated serum lactate and pyruvate), a history of transient neonatal hypoglycemia, and features of Leigh syndrome; she died at age 28 months. Plasma amino acid analysis in the patient initially showed increased leucine, isoleucine, and valine. Urine organic acid analysis showed mild to moderate increases of lactic, 2-hydroxybutyric, 3-hydroxybutyric, alpha-ketoglutaric, and 3-hydroxyisovaleric acids. She died at age 28 months. Activities of the PDC and E3 in patient lymphocytes were 26% and 2% of control values, respectively, and in patient fibroblasts were 11% and 14%, respectively. KGDC activity in fibroblasts was 20%. Corresponding values in the clinically unaffected parents were about 50% of normal, except for KGDC, which was normal. These findings suggested that a partial reduction in E3 is not rate-limiting for KGDC activity in fibroblasts. Glycine was also not increased in the patient. </p><p>In 2 unrelated patients of Ashkenazi-Jewish origin with DLDD, Elpeleg et al. (1997) identified the 105insA mutation in the DLD gene. The 2 patients were heterozygotes for the mutation; no other mutation was identified in the coding region. Heterozygosity for the 105insA mutation was also identified in the cDNA of the father and 1 brother of patient 1, and in the mother and 1 sister of patient 2. Because the enzymatic activity of lipoamide dehydrogenase in muscle tissue of both patients was reduced to 8 to 20% of the control mean, Elpeleg et al. (1997) presumed that both patients were compound heterozygotes for this and another unidentified mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, ARG495GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964989,
|
|
|
|
|
|
|
|
ClinVar: RCV000012746
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg495-to-gly (R495G) mutation in the DLD gene that was found in compound heterozygous state in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900) by Hong et al. (1996), see 238331.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, GLY229CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964990,
|
|
|
|
|
|
gnomAD: rs121964990,
|
|
|
|
|
|
ClinVar: RCV000012744, RCV000185853, RCV000624277, RCV004528103
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a series of 7 Ashkenazi Jewish families with dihydrolipoyl dehydrogenase deficiency (DLDD; 246900), Shaag et al. (1999) identified a mutation in the DLD gene resulting in a gly229-to-cys (G229C) substitution at a highly conserved residue in the NAD(+)-binding domain. The G229C mutation accounted for 12 of 14 mutant alleles. G229C corresponds to G194C in the mature protein (Odievre et al., 2005). In a sample of 845 anonymous individuals of Ashkenazi Jewish origin, 9 heterozygotes for the G194C mutation were identified, yielding a carrier rate of 1:94. The other 2 alleles in the series had a previously identified insertion mutation (238331.0003). The disease course and age at onset were highly variable. Some patients had few neurologic sequelae and long survival. Two patients presented immediately after birth, 9 around age 2 years, and 2 as adults. All had recurrent episodes of vomiting, abdominal pain, and hepatomegaly, usually associated with neurologic signs during the episodes. Episodes were associated with lactic acidosis, abnormal liver enzymes, and prolonged prothrombin time. Biochemical anomalies, such as increased branched-chain amino acids and increased alpha-ketoacids were not commonly found. The 2 patients who presented neonatally had residual neurologic damage with attention deficit-hyperactivity disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or as adults suffered from exertional fatigue between episodes of decompensation but were otherwise asymptomatic and showed normal psychomotor development. Two patients died because of intractable metabolic acidosis and multiorgan failure. In all patients, E3 activity was reduced to 8 to 21% of the control value in muscle or lymphocytes. In 4 patients tested, the E3 protein in muscle was reduced to 20 to 60% of control. </p><p>Hong et al. (2003) reported 2 sibs, born of consanguineous Palestinian Arab Muslim parents, with E3 deficiency due to homozygosity for the G194C mutation. A girl died in infancy during an episode of repeated vomiting associated with encephalopathy. Two previous sibs had died under similar circumstances. A brother had recurrent episodes of vomiting associated with encephalopathy from age 8 months. Examination at age 10 years showed generalized muscle weakness and wasting, ataxic gait, hepatomegaly, and lactic acidemia. He was treated with riboflavin, coenzyme Q, biotin, and carnitine. Six years later, he was functioning well at a normal school, but had slight ataxia and intention tremor. Two additional patients, both of Ashkenazi Jewish descent, had a severe form of E3 deficiency and the G194C mutation. One had repeated episodes of hypoglycemia and was in a persistent vegetative state at age 4 years; he died soon after. A girl had recurrent episodes of repeated vomiting and acidosis since infancy; she died of hepatic failure at age 5 years. All patients had decreased levels of the E3 protein (range, 35-68% of controls) and decreased E3 activity (8-33% of controls). Hong et al. (2003) emphasized the favorable outcome in the 1 child treated with riboflavin and additional supplements. </p><p>By in vitro functional expression studies, Ambrus et al. (2011) found that the G194C mutant protein caused no significant changes in LADH activity but did result in significantly increased generation of reactive oxygen species. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, ILE393THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964991,
|
|
|
|
|
|
|
|
ClinVar: RCV000012747
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), Grafakou et al. (2003) identified heterozygosity for 2 mutations in the DLD gene: an ile393-to-thr (I393T) substitution in exon 11, postulated to interfere with protein dimerization, and an IVS9+1G-A change at a consensus splice site (238331.0008). I393T corresponds to I358T in the mature protein (Odievre et al., 2005). The I358T mutation cosegregated with a polymorphism, 1422A-C, in exon 13; both appeared to be homozygous in cDNA studies, suggesting that the mRNA product of the splice site mutation was unstable. One year after presentation, the patient developed a stroke-like episode, and brain MRI showed symmetric hyperintensity consistent with Leigh syndrome (256000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, IVS9DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1328820332,
|
|
|
|
|
|
gnomAD: rs1328820332,
|
|
|
|
|
|
ClinVar: RCV000012749
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the splice site mutation in the DLD gene (IVS9+1G-A) that was found in compound heterozygous state in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900) by Grafakou et al. (2003), see 238331.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, GLU375LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964992,
|
|
|
|
|
|
gnomAD: rs121964992,
|
|
|
|
|
|
ClinVar: RCV000012751, RCV000185859, RCV001266054, RCV002251899, RCV004528104
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-week-old boy with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), Cerna et al. (2001) identified compound heterozygosity for 2 mutations in the DLD gene: a 1123G-A transition resulting in a glu375-to-lys (E375K) substitution and a 1081A-G transition resulting in a met361-to-val (M361V; 238331.0010) substitution. E375K and M361V correspond to E340K and M326V in the mature protein, respectively (Odievre et al., 2005). DLD activity in the patient's lymphocytes, muscle mitochondria, and fibroblasts was less than 5% of control values, and Western blot analysis showed a decrease in DLD protein levels to 40% of controls. </p><p>Cameron et al. (2006) noted that the E375K mutation occurs at a conserved residue in the central domain of DLD. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, MET361VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964993,
|
|
|
|
|
|
gnomAD: rs121964993,
|
|
|
|
|
|
ClinVar: RCV000012752
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the met361-to-val (M361V) mutation in the DLD gene that was found in compound heterozygous state in a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900) by Cerna et al. (2001), see 238331.0009. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, ASP479VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514649,
|
|
|
|
|
|
|
|
ClinVar: RCV000033216
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-month-old girl of Muslim origin with a severe neurodegenerative form of dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), Shany et al. (1999) identified a homozygous 1436A-T transversion in the DLD gene, resulting in an asp479-to-val (D479V) substitution, which is a D444V change in the processed protein (Odievre et al., 2005). The substitution occurs in the interface domain of the DLD dimer, which was postulated to perturb the stability of the homodimer. The patient reported by Shany et al. (1999) presented on the third day of life with apathy, poor feeding, and lethargy. Laboratory studies showed hypoglycemia and severe lactic acidosis, but normal levels of branched-chain keto acids and alpha-ketoglutarate. Muscle biopsy showed no activity of the pyruvate dehydrogenase complex, severely decreased activity of the alpha-ketoglutarate dehydrogenase complex (2%), and decreased DLD activity at 15% of controls. Each of her unaffected parents had about 50% reduced DLD protein activity. She had recurrent episodes of metabolic acidosis, often triggered by infection. Clinical features included microcephaly, lack of psychomotor development, blindness, deafness, hypotonia, brisk reflexes, and mild hypertrophic cardiomyopathy. Shany et al. (1999) noted that the phenotypic severity in this patient was not correlated with residual DLD protein activity, since the G229C mutation (238331.0006) was associated with even less activity (7%), but a milder phenotype. </p><p>Babady et al. (2007) found that the D444V mutant protein had increased proteolytic activity compared to wildtype and that this proteolytic activity correlated with the monomer fraction of the mutant DLD protein. The appearance of this proteolytic activity may have contributed to the phenotypic severity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, ARG482GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514650,
|
|
|
|
|
|
|
|
ClinVar: RCV000033217
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Algerian sibs, born of consanguineous parents, with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), Odievre et al. (2005) identified a homozygous 1444A-G transition in exon 13 of the DLD gene, resulting in an arg482-to-gly (R482G) substitution (R447G in the processed protein) in the dimer interface domain. The patients had originally been reported by Bonnefont et al. (1992) as having alpha-ketoglutarate dehydrogenase deficiency. They had a severe form of the disorder, resulting in death in all by age 30 months. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DLD, ILE47THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514651,
|
|
|
|
|
|
|
|
ClinVar: RCV000033218
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 second-cousin Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), Cameron et al. (2006) identified compound heterozygosity for 2 mutations in the DLD gene. Both patients carried a heterozygous T-to-C transition in exon 3, resulting in an ile47-to-thr (I47T) substitution at a highly conserved region in the FAD functional domain. One patient had G229C (238331.0006) on the other allele, and the other had E375K (238331.0009) on the other allele. All unaffected parents were heterozygous for 1 of the mutations. Both patients had decreased activities of the KGDH (25% and 44%, respectively) and BCKDH (58% and 62%, respectively) complexes, but PDH complex activity was at the low end of normal (69% and 59%, respectively). DLD activity was decreased in both patients. The patient with the G229C mutation had a milder phenotype compared to the patient without that mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Steiert et al. (1990)
|
|
</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">
|
|
Ambrus, A., Torocsik, B., Tretter, L., Ozohanics, O., Adam-Vizi, V.
|
|
<strong>Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase.</strong>
|
|
Hum. Molec. Genet. 20: 2984-2995, 2011.
|
|
|
|
|
|
[PubMed: 21558426]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddr202]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Babady, N. E., Pang, Y.-P., Elpeleg, O., Isaya, G.
|
|
<strong>Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 6158-6163, 2007.
|
|
|
|
|
|
[PubMed: 17404228]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0610618104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A.
|
|
<strong>Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.</strong>
|
|
J. Pediat. 121: 255-258, 1992.
|
|
|
|
|
|
[PubMed: 1640293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(05)81199-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H.
|
|
<strong>Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.</strong>
|
|
Am. J. Med. Genet. 140A: 1542-1552, 2006.
|
|
|
|
|
|
[PubMed: 16770810]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31313]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cerna, L., Wenchich, L., Hansikova, H., Kmoch, S., Peskova, K., Chrastina, P., Brynda, J., Zeman, J.
|
|
<strong>Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.</strong>
|
|
Med. Sci. Monit. 7: 1319-1325, 2001.
|
|
|
|
|
|
[PubMed: 11687750]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Craigen, W. J.
|
|
<strong>Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.</strong>
|
|
Pediat. Neurol. 14: 69-71, 1996.
|
|
|
|
|
|
[PubMed: 8652022]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0887-8994(96)00005-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elpeleg, O. N., Shaag, A., Glustein, J. Z., Anikster, Y., Joseph, A., Saada, A.
|
|
<strong>Lipoamide dehydrogenase deficiency in Ashkenazi Jews: an insertion mutation in the mitochondrial leader sequence.</strong>
|
|
Hum. Mutat. 10: 256-257, 1997.
|
|
|
|
|
|
[PubMed: 9298831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<256::AID-HUMU16>3.0.CO;2-Z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Feigenbaum, A. S., Robinson, B. H.
|
|
<strong>The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements.</strong>
|
|
Genomics 17: 376-381, 1993.
|
|
|
|
|
|
[PubMed: 8406489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1335]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grafakou, O., Oexle, K., van den Heuvel, L., Smeets, R., Trijbels, F., Goebel, H. H., Bosshard, N., Superti-Furga, A., Steinmann, B., Smeitink, J.
|
|
<strong>Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations: description of the first E3 splice site mutation.</strong>
|
|
Europ. J. Pediat. 162: 714-718, 2003.
|
|
|
|
|
|
[PubMed: 12925875]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00431-003-1282-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamosh, A., Johnston, M. V.
|
|
<strong>Nonketotic hyperglycinemia. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001. Pp. 2065-2078.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S.
|
|
<strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong>
|
|
Hum. Molec. Genet. 5: 1925-1930, 1996.
|
|
|
|
|
|
[PubMed: 8968745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.12.1925]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S.
|
|
<strong>Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.</strong>
|
|
J. Inherit. Metab. Dis. 26: 816-818, 2003.
|
|
|
|
|
|
[PubMed: 14765544]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/b:boli.0000010004.12053.5b]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, M., Yang, H.-S., Johanning, G. L., Patel, M. S.
|
|
<strong>Characterization of the mouse dihydrolipoamide dehydrogenase (Dld) gene: genomic structure, promoter sequence, and chromosomal localization.</strong>
|
|
Genomics 41: 320-326, 1997.
|
|
|
|
|
|
[PubMed: 9169128]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.4670]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S.
|
|
<strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.
|
|
|
|
|
|
[PubMed: 8506365]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.90.11.5186]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P.
|
|
<strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. (Abstract)</strong>
|
|
Hum. Mutat. 25: 323-324, 2005. Note: Full Article Online.
|
|
|
|
|
|
[PubMed: 15712224]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.9319]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Olson, S., Song, B. J., Huh, T.-L., Chi, Y.-T., Veech, R. L., McBride, O. W.
|
|
<strong>Three genes for enzymes of the pyruvate dehydrogenase complex map to human chromosomes 3, 7, and X.</strong>
|
|
Am. J. Hum. Genet. 46: 340-349, 1990. Note: Erratum: Am. J. Hum. Genet. 46: 1235 only, 1990.
|
|
|
|
|
|
[PubMed: 1967901]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otulakowski, G., Robinson, B. H.
|
|
<strong>Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase.</strong>
|
|
J. Biol. Chem. 262: 17313-17318, 1987.
|
|
|
|
|
|
[PubMed: 3693355]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otulakowski, G., Robinson, B. H., Willard, H. F.
|
|
<strong>Gene for lipoamide dehydrogenase maps to human chromosome 7.</strong>
|
|
Somat. Cell Molec. Genet. 14: 411-414, 1988.
|
|
|
|
|
|
[PubMed: 3399966]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01534650]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Petrat, F., Paluch, S., Dogruoz, E., Dorfler, P., Kirsch, M., Korth, H.-G., Sustmann, R., de Groot, H.
|
|
<strong>Reduction of Fe(III) ions complexed to physiological ligands by lipoyl dehydrogenase and other flavoenzymes in vitro: implications for an enzymatic reduction of Fe(III) ions of the labile iron pool.</strong>
|
|
J. Biol. Chem. 278: 46403-46413, 2003.
|
|
|
|
|
|
[PubMed: 12963736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M305291200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pons, G., Raefsky-Estrin, C., Carothers, D. J., Pepin, R. A., Javed, A. A., Jesse, B. W., Ganapathi, M. K., Samols, D., Patel, M. S.
|
|
<strong>Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human alpha-ketoacid dehydrogenase complexes.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 1422-1426, 1988.
|
|
|
|
|
|
[PubMed: 3278312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.85.5.1422]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T.
|
|
<strong>Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.</strong>
|
|
Europ. J. Pediat. 145: 271-274, 1986.
|
|
|
|
|
|
[PubMed: 3769994]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00439399]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sakata, Y., Owada, Y., Sato, K., Kojima, K., Hisanaga, K., Shinka, T., Suzuki, Y., Aoki, Y., Satoh, J., Kondo, H., Matsubara, Y., Kure, S.
|
|
<strong>Structure and expression of the glycine cleavage system in rat central nervous system.</strong>
|
|
Molec. Brain Res. 94: 119-130, 2001.
|
|
|
|
|
|
[PubMed: 11597772]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0169-328x(01)00225-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scherer, S. W., Otulakowski, G., Robinson, B. H., Tsui, L.-C.
|
|
<strong>Localization of the human dihydrolipoamide dehydrogenase gene (DLD) to 7q31-q32.</strong>
|
|
Cytogenet. Cell Genet. 56: 176-177, 1991.
|
|
|
|
|
|
[PubMed: 2055113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000133081]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N.
|
|
<strong>Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.</strong>
|
|
Am. J. Med. Genet. 82: 177-182, 1999.
|
|
|
|
|
|
[PubMed: 9934985]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N.
|
|
<strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong>
|
|
Biochem. Biophys. Res. Commun. 262: 163-166, 1999.
|
|
|
|
|
|
[PubMed: 10448086]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1999.1133]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Steiert, P. S., Stauffer, L. T., Stauffer, G. V.
|
|
<strong>The lpd gene product functions as the L protein in the Escherichia coli glycine cleavage enzyme system.</strong>
|
|
J. Bacteriol. 172: 6142-6144, 1990.
|
|
|
|
|
|
[PubMed: 2211531]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/jb.172.10.6142-6144.1990]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vaubel, R. A., Rustin, P., Isaya, G.
|
|
<strong>Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells.</strong>
|
|
J. Biol. Chem. 286: 40232-40245, 2011.
|
|
|
|
|
|
[PubMed: 21930696]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M111.274415]
|
|
|
|
|
|
</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">
|
|
Cassandra L. Kniffin - updated : 2/28/2013
|
|
</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 : 8/17/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/15/2016<br>carol : 07/09/2016<br>carol : 9/1/2015<br>carol : 7/8/2015<br>mcolton : 7/7/2015<br>carol : 9/17/2013<br>terry : 3/28/2013<br>carol : 3/8/2013<br>carol : 3/5/2013<br>ckniffin : 2/28/2013<br>alopez : 6/13/2005<br>carol : 6/22/2001<br>carol : 5/17/2001<br>carol : 5/2/2001<br>carol : 5/2/2001<br>dkim : 11/13/1998<br>carol : 7/16/1998<br>joanna : 1/23/1997<br>mimadm : 3/11/1994<br>carol : 8/17/1992
|
|
</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>
|
|
|
|
|