5030 lines
413 KiB
Text
5030 lines
413 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
|
|
|
|
- *609058 - METHYLMALONYL-CoA MUTASE; MMUT
|
|
|
|
|
|
- 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=609058"><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">*609058</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/609058">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=ENSG00000146085;t=ENST00000274813" 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=4594" 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=609058" 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=ENSG00000146085;t=ENST00000274813" 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_000255,XM_005249143" 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_000255" 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=609058" 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=02014&isoform_id=02014_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/MMUT" 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/187452,16740839,30583707,62087270,119624734,119624735,119624736,156105689,158258573,189069160,317373575,490347572,490347594,490347605,490347612,490347618,490347629,490347649,490347657,490347671,490347677,490347710,490347730,490347737,490347764,490347779,490347803,490347815,490347823,490347840,530382073,534304885,743944730,743944732,827746623,827746625,893670060,957949804,957949807,1386751315,1386751317,1386751319,1386751321,1386751323,1386751325,1386751327,1386751329,1386751331,1386751333,1386751335,1386751337,2462608652" 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/P22033" 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=4594" 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=ENSG00000146085;t=ENST00000274813" 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=MMUT" 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=MMUT" 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+4594" 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/MMUT" 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:4594" 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/4594" 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=chr6&hgg_gene=ENST00000274813.4&hgg_start=49430360&hgg_end=49463253&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:7526" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7526" 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/mmut" 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=609058[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=609058[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000146085" 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=MMUT" 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=MMUT" 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=MMUT" 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="http://databases.lovd.nl/genomed/home.php?select_db=MUT" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MMUT&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/PA31327" 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:7526" 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:97239" 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/MMUT#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:97239" 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/4594/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002849/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=4594" 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=WBGene00014202;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-010430-3" 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:4594" 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=MMUT&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
609058
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
METHYLMALONYL-CoA MUTASE; MMUT
|
|
|
|
</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">
|
|
MUT<br />
|
|
METHYLMALONYL-CoA ISOMERASE<br />
|
|
MCM
|
|
</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=MMUT" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MMUT</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/6/568?start=-3&limit=10&highlight=568">6p12.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:49430360-49463253&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'})">6:49,430,360-49,463,253</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/6/568?start=-3&limit=10&highlight=568">
|
|
6p12.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Methylmalonic aciduria, mut(0) type
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/251000"> 251000 </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/609058" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/609058" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Methylmalonyl-CoA mutase (MUT) (<a href="https://enzyme.expasy.org/EC/5.4.99.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 5.4.99.2</a>) is a mitochondrial enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. MUT activity requires 5-prime-deoxyadenosylcobalamin (AdoCbl), a coenzyme form of vitamin B12.</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>By screening human placenta and liver cDNA libraries with an anti-MCM antibody, <a href="#19" class="mim-tip-reference" title="Ledley, F. D., Lumetta, M., Nguyen, P. N., Kolhouse, J. F., Allen, R. H. <strong>Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut cell lines.</strong> Proc. Nat. Acad. Sci. 85: 3518-3521, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2453061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2453061</a>] [<a href="https://doi.org/10.1073/pnas.85.10.3518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2453061">Ledley et al. (1988)</a> isolated a partial MUT cDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2453061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#15" class="mim-tip-reference" title="Jansen, R., Kalousek, F., Fenton, W. A., Rosenberg, L. E., Ledley, F. D. <strong>Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction.</strong> Genomics 4: 198-205, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2567699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2567699</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90300-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2567699">Jansen et al. (1989)</a> isolated a full-length cDNA corresponding to the MUT gene from a human liver cDNA library. The deduced 742-amino acid protein has a molecular mass of 82.2 kD; the mature protein is 78.5 kD. The mitochondrial leader sequence comprises 32 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2567699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#25" class="mim-tip-reference" title="Nham, S.-U., Wilkemeyer, M. F., Ledley, F. D. <strong>Structure of the human methylmalonyl-CoA mutase (MUT) locus.</strong> Genomics 8: 710-716, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1980486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1980486</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90259-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1980486">Nham et al. (1990)</a> determined that the MUT gene contains 13 exons spanning more than 35 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1980486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="Ledley, F. D., vanTuinen, P., Ledbetter, S. A., Ledbetter, D. <strong>Assignment of methylmalonyl CoA mutase locus to human chromosome 6. (Abstract)</strong> Cytogenet. Cell Genet. 46: 646 only, 1987."None>Ledley et al. (1987)</a> assigned the methylmalonyl-CoA mutase locus to chromosome 6p by use of a full-length MCM cDNA clone from a human liver cDNA library. By Southern blot analysis of DNA from human-hamster somatic cell hybrid cell lines, <a href="#20" class="mim-tip-reference" title="Ledley, F. D., Lumetta, M. R., Zoghbi, H. Y., vanTuinen, P., Ledbetter, S. A., Ledbetter, D. H. <strong>Mapping of human methylmalonyl CoA mutase (MUT) locus on chromosome 6.</strong> Am. J. Hum. Genet. 42: 839-846, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2897160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2897160</a>]" pmid="2897160">Ledley et al. (1988)</a> assigned the MUT locus to 6p23-q12. By in situ hybridization, the locus was further localized to 6p21.2-p12. A highly informative RFLP was identified at the MCM gene locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2897160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 deletion mapping in cell lines with 6p deletions, <a href="#35" class="mim-tip-reference" title="Zoghbi, H. Y., O'Brien, W. E., Ledley, F. D. <strong>Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6.</strong> Genomics 3: 396-398, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907507</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90135-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2907507">Zoghbi et al. (1988)</a> demonstrated that the MUT gene is located on 6p, proximal to GLO1 (<a href="/entry/138750">138750</a>). By use of a HindIII polymorphism identified by the MUT cDNA, they demonstrated the linkage relationships to HLA in reference CEPH families; the maximum lod score for MUT versus HLA was 3.04 at a recombination fraction of 0.28. <a href="#5" class="mim-tip-reference" title="Blanche, H., Zoghbi, H. Y., Jabs, E. W., de Gouyon, B., Zunec, R., Dausset, J., Cann, H. M. <strong>A centromere-based genetic map of the short arm of human chromosome 6.</strong> Genomics 9: 420-428, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2032717/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2032717</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90407-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2032717">Blanche et al. (1991)</a> presented a genetic map of 6p which included RFLP mapping of the MUT locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2032717+2907507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 a study of recombinant inbred and congenic strains, <a href="#31" class="mim-tip-reference" title="Sertic, J., Vincek, V., Ledley, F. D., Figueroa, F., Klein, J. <strong>Mapping of the L-methylmalonyl-CoA mutase gene to mouse chromosome 17.</strong> Genomics 6: 560-564, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970332</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90487-f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1970332">Sertic et al. (1990)</a> demonstrated that the mouse equivalent of the MUT gene is located on chromosome 17. <a href="#33" class="mim-tip-reference" title="Threadgill, D. W., Wilkemeyer, M., Womack, J. E., Ledley, F. D. <strong>Localization of the murine methylmalonyl CoA mutase (Mut) locus on chromosome 17 by in situ hybridization.</strong> Cytogenet. Cell Genet. 53: 112-114, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973376</a>] [<a href="https://doi.org/10.1159/000132907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1973376">Threadgill et al. (1990)</a> assigned the gene to mouse chromosome 17 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1970332+1973376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Ledley, F. D., Crane, A. M., Lumetta, M. <strong>Heterogeneous alleles and expression of methylmalonyl CoA mutase in mut methylmalonic acidemia.</strong> Am. J. Hum. Genet. 46: 539-547, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1968706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1968706</a>]" pmid="1968706">Ledley et al. (1990)</a> could demonstrate no gross abnormalities of the MCM gene by Southern blot analysis in cell lines from patients with methylmalonic acidemia (MMA; see <a href="/entry/251000">251000</a>). By other methods, however, they concluded that there are several independent alleles giving different levels of mRNA expression and biochemical phenotype of the cultured cells. The studies provided a molecular explanation for the wide phenotypic spectrum observed in the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1968706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MMA mut(0), defined as having no residual enzyme activity, <a href="#16" class="mim-tip-reference" title="Jansen, R., Ledley, F. D. <strong>Heterozygous mutations at the mut locus in fibroblasts with mut-0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning.</strong> Am. J. Hum. Genet. 47: 808-814, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1977311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1977311</a>]" pmid="1977311">Jansen and Ledley (1990)</a> identified compound heterozygosity for 2 mutations in the MUT gene (<a href="#0001">609058.0001</a> and <a href="#0002">609058.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1977311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MMA mut(-), defined as having some residual enzyme activity, who had been reported by <a href="#17" class="mim-tip-reference" title="Ledley, F. D., Crane, A. M., Lumetta, M. <strong>Heterogeneous alleles and expression of methylmalonyl CoA mutase in mut methylmalonic acidemia.</strong> Am. J. Hum. Genet. 46: 539-547, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1968706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1968706</a>]" pmid="1968706">Ledley et al. (1990)</a>, <a href="#8" class="mim-tip-reference" title="Crane, A. M., Jansen, R., Andrews, E. R., Ledley, F. D. <strong>Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut(-) methylmalonic aciduria.</strong> J. Clin. Invest. 89: 385-391, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346616</a>] [<a href="https://doi.org/10.1172/JCI115597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1346616">Crane et al. (1992)</a> identified a homozygous mutation in the MUT gene (<a href="#0005">609058.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1968706+1346616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Crane, A. M., Ledley, F. D. <strong>Clustering of mutations in methylmalonyl CoA mutase associated with mut(-) methylmalonic acidemia.</strong> Am. J. Hum. Genet. 55: 42-50, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7912889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7912889</a>]" pmid="7912889">Crane and Ledley (1994)</a> identified 4 novel mutations clustered near the C terminus of the MUT protein in patients with MMA. Three of the patients responded to cobalamin therapy. Each mutation showed interallelic complementation in cotransfection assays with clones bearing an R93H mutation (<a href="#0004">609058.0004</a>). The findings suggested that the C-terminal region of the protein represents a cobalamin-binding domain. The location of this domain, as well as a pattern of sequence preservation between the homologous human and Propionobacterium shermanii enzymes, suggested a mechanism for interallelic complementation in which the cobalamin-binding defect is complemented in trans from the heterologous subunits of the dimer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7912889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Drennan, C. L., Matthews, R. G., Rosenblatt, D. S., Ledley, F. D., Fenton, W. A., Ludwig, M. L. <strong>Molecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: deductions from the structure of methionine synthase.</strong> Proc. Nat. Acad. Sci. 93: 5550-5555, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8643613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8643613</a>] [<a href="https://doi.org/10.1073/pnas.93.11.5550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8643613">Drennan et al. (1996)</a> made deductions concerning the molecular basis for dysfunction of some mutant forms of MCM by aligning the sequence of this gene with that of other B12-dependent enzymes, including the C-terminal portion of the cobalamin-binding region of methionine synthase (<a href="/entry/156570">156570</a>) from E. coli, the structure of which had been determined by x-ray crystallography. Previously identified mutants such as gly623-to-arg (<a href="#0008">609058.0008</a>) were predicted to interfere with the structure and/or stability of the loop that carries histidine-627, the presumed lower axial ligand to the cobalt of adenosylcobalamin. A mutant such as gly703-to-arg (<a href="#0009">609058.0009</a>), which maps to the binding site for the dimethylbenzimidazole nucleotide substituent of adenosylcobalamin, was predicted to block the binding of adenosylcobalamin because of the substitution of a large amino acid side chain for glycine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8643613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Janata, J., Kogekar, N., Fenton, W. A. <strong>Expression and kinetic characterization of methylmalonyl-CoA mutase from patients with the mut- phenotype: evidence for naturally occurring interallelic complementation.</strong> Hum. Molec. Genet. 6: 1457-1464, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285782</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1457" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285782">Janata et al. (1997)</a> identified 6 missense mutations producing amino acid changes in MUT cDNA from patients with mut(-) MMA. Two of the mutations had been reported in other patients. In 1 cell line, which the authors referred to as doubly heterozygous (compound heterozygous is the correct description), expression studies indicated that neither of the constituent mutant enzymes had a Km corresponding to the lower of the 2 estimated from the extract data. The finding was thought to reflect the natural occurrence of interallelic complementation in vivo in this cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Adjalla, C. E., Hosack, A. R., Gilfix, B. M., Lamothe, E., Sun, S., Chan, A., Evans, S., Matiaszuk, N. V., Rosenblatt, D. S. <strong>Seven novel mutations in mut methylmalonic aciduria.</strong> Hum. Mutat. 11: 270-274, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554742</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<270::AID-HUMU3>3.0.CO;2-T" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554742">Adjalla et al. (1998)</a> identified 7 novel mutations in mut methylmalonic aciduria and noted that 23 mutations had previously been identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Acquaviva, C., Benoist, J.-F., Callebaut, I., Guffon, N., Ogier de Baulny, H., Touati, G., Aydin, A., Porquet, D., Elion, J. <strong>N219Y, a new frequent mutation among mut-0 forms of methylmalonic acidemia in Caucasian patients.</strong> Europ. J. Hum. Genet. 9: 577-582, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11528502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11528502</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11528502">Acquaviva et al. (2001)</a> reported a novel MUT missense mutation, asn219 to tyr (N219Y; <a href="#0010">609058.0010</a>), in 5 unrelated families of French and Turkish descent from a population of 19 patients with MCM apoenzyme deficiency. All the patients exhibited a severe mut(0) methylmalonic acidemia phenotype, and 3 of them were homozygous for the N219Y mutation. The findings represented the first frequent MUT mutation reported in the Caucasian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11528502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#7" class="mim-tip-reference" title="Champattanachai, V., Ketudat Cairns, J. R., Shotelersuk, V., Keeratichamroen, S., Sawangareetrakul, P., Srisomsap, C., Kaewpaluek, V., Svasti, J. <strong>Novel mutations in a Thai patient with methylmalonic acidemia.</strong> Molec. Genet. Metab. 79: 300-302, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12948746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12948746</a>] [<a href="https://doi.org/10.1016/s1096-7192(03)00106-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12948746">Champattanachai et al. (2003)</a> reported 2 novel mutations in a Thai patient with mut(0) methylmalonic acidemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12948746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Acquaviva, C., Benoist, J.-F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D., Elion, J. <strong>Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(0) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.</strong> Hum. Mutat. 25: 167-176, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15643616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15643616</a>] [<a href="https://doi.org/10.1002/humu.20128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15643616">Acquaviva et al. (2005)</a> analyzed a cohort of 40 MCM-deficient patients with MMA affected by either the mut(0) or mut(-) form of the disease. By direct sequencing of cDNA and genomic DNA of the MUT gene, they detected 42 mutations, 29 of which were novel. These included 5 frameshift mutations (insertion, deletion, or duplication of a single nucleotide), 5 sequence modifications in consensus splice sites, 6 nonsense and 12 missense mutations, and a large genomic deletion including exon 12. They explored how the 12 novel missense mutations might cause the observed phenotype by mapping them onto a 3-dimensional model of the human MCM generated by homology with the enzyme in P. shermanii. <a href="#2" class="mim-tip-reference" title="Acquaviva, C., Benoist, J.-F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D., Elion, J. <strong>Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(0) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.</strong> Hum. Mutat. 25: 167-176, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15643616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15643616</a>] [<a href="https://doi.org/10.1002/humu.20128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15643616">Acquaviva et al. (2005)</a> increased the number of mutations in the MUT gene to 84 and discussed their prevalence and distribution throughout the coding sequence in relation to enzyme structure. The authors noted that most of the mutations in the MUT gene are private, with no demonstrated hotspots. Prior to their study only 2 recurrent mutations had been described: glu 117 to ter (E117X; <a href="#0006">609058.0006</a>) and N219Y, which had high frequencies in Japanese and Caucasian populations, respectively. <a href="#2" class="mim-tip-reference" title="Acquaviva, C., Benoist, J.-F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D., Elion, J. <strong>Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(0) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.</strong> Hum. Mutat. 25: 167-176, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15643616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15643616</a>] [<a href="https://doi.org/10.1002/humu.20128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15643616">Acquaviva et al. (2005)</a> confirmed a high frequency of N219Y in Caucasians: 12 of their 40 patients carried the mutation in a heterozygous or homozygous state, which represented 19% of the alleles tested. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15643616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Worgan, L. C., Niles, K., Tirone, J. C., Hofmann, A., Verner, A., Sammak, A., Kucic, T., Lepage, P., Rosenblatt, D. S. <strong>Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.</strong> Hum. Mutat. 27: 31-43, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16281286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16281286</a>] [<a href="https://doi.org/10.1002/humu.20258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16281286">Worgan et al. (2006)</a> sequenced the MUT gene in 160 patients with mut MMA. Mutations were identified in 96% of disease alleles. Mutations were distributed through all coding exons, but predominantly in exons 2, 3, 6, and 11. A total of 116 different mutations, 68 of which were novel, were identified; 53% were missense mutations, 22% deletions, duplications or insertions, 16% were nonsense mutations, and 9% were splice site mutations. Sixty-one of the mutations were identified in only 1 family. A novel mutation in exon 2, R108C (<a href="#0011">609058.0011</a>), was identified in 16 of 27 Hispanic patients. SNP genotyping data demonstrated that Hispanic patients with this mutation shared a common haplotype. Three other mutations were seen exclusively in Hispanic patients. Seven mutations were seen almost exclusively in black patients, including the G717V mutation (<a href="#0005">609058.0005</a>), which was identified in 12 of 29 black patients. Two mutations were seen only in Asian patients. Some frequently identified mutations were not population-specific and were identified in patients of various ethnic backgrounds. Some of these mutations were found in mutation clusters in exons 2, 3, 6, and 11, suggesting that they represented recurrent mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16281286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> described 3 genomic alterations--1 in the MUT gene, 1 in the PCCA gene (<a href="/entry/232000">232000</a>), and 1 in the PCCB gene (<a href="/entry/232050">232050</a>)--that were responsible for aberrant insertion of intronic sequences in patients' mRNA. The authors targeted the aberrant intronic pseudoexons with antisense morpholino oligonucleotides (AMOs) that prevented aberrant splicing, thus generating normal mRNA which was translated into functional protein, achieving therapeutic correction of the defect in methylmalonic acidemia (<a href="/entry/251000">251000</a>) or propionic acidemia (<a href="/entry/606054">606054</a>). No effect on MCM activity was obtained after AMO treatment in cell lines bearing different mutations and exhibiting some levels of intronic MUT insertions. <a href="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> suggested that this therapeutic strategy would be potentially applicable to a large number of cases with deep intronic changes that remained undetected by standard mutation-detection techniques at that time. The major issues facing clinical applications of morpholino analogs of oligonucleotides concerned safe delivery and optimal dose determination for each tissue involved. Efficient and nontoxic delivery of AMO to the liver, which would be the target tissue in this disorder, was one major challenge to be overcome before the practical use of AMO in patients with methylmalonic acidemia could be envisaged. In Duchenne muscular dystrophy (<a href="/entry/310200">310200</a>), antisense oligonucleotides have been administered intravenously, achieving splicing modulation to restore the coding frame for dystrophin (<a href="#32" class="mim-tip-reference" title="Takeshima, Y., Yagi, M., Wada, H., Ishibashi, K., Nishiyama, A., Kakumoto, M., Sakaeda, T., Saura, R., Okumura, K., Matsuo, M. <strong>Intravenous infusion of an antisense oligonucleotide results in exon skipping in muscle dystrophin mRNA of Duchenne muscular dystrophy.</strong> Pediat. Res. 59: 690-694, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16627883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16627883</a>] [<a href="https://doi.org/10.1203/01.pdr.0000215047.51278.7c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16627883">Takeshima et al., 2006</a>). The efficacy of antisense therapeutics for splicing correction must be determined in each disease model and for each deleterious splicing event. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17966092+16627883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To understand the pathologic mechanisms leading to MMA, <a href="#13" class="mim-tip-reference" title="Forny, P., Froese, D. S., Suormala, T., Yue, W. W., Baumgartner, M. R. <strong>Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.</strong> Hum. Mutat. 35: 1449-1458, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25125334[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/10.1002/humu.22633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125334">Forny et al. (2014)</a> assessed stability and enzymatic effects of 23 MMUT missense mutations expressed in 2 recombinant expression systems. All 23 mutants had decreased enzymatic function. Stability was assessed based on thermolability and folding of the mutant protein. Six mutations led to abnormal folding, and 4 others led to increased thermolability. In evaluating enzymatic defects in the MMUT mutants, 4 mutations led to isolated Km defects, and 6 mutations led to isolated catalytic defects. Three mutations led to increased Km and thermolability, 1 mutation led to catalytic dysfunction and thermolability, and 3 mutations led to both folding and catalytic defects. <a href="#13" class="mim-tip-reference" title="Forny, P., Froese, D. S., Suormala, T., Yue, W. W., Baumgartner, M. R. <strong>Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.</strong> Hum. Mutat. 35: 1449-1458, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25125334[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/10.1002/humu.22633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125334">Forny et al. (2014)</a> then tested whether osmolytes could stabilize the mutant proteins and found that soluble protein yield was increased with glycerol or TMAO in some mutants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Using 3D organotypic brain cell cultures derived from embryos of a brain-specific Mut -/- mouse, <a href="#29" class="mim-tip-reference" title="Remacle, N., Forny, P., Cudre-Cung, H.-P., Gonzalez-Melo, M., do Vale-Pereira, S., Henry, H., Teav, T., Gallart-Ayala, H., Braissant, O., Baumgartner, M., Ballhausen, D. <strong>New in vitro model derived from brain-specific Mut-/- mice confirms cerebral ammonium accumulation in methylmalonic aciduria.</strong> Molec. Genet. Metab. 124: 266-277, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29934063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29934063</a>] [<a href="https://doi.org/10.1016/j.ymgme.2018.06.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29934063">Remacle et al. (2018)</a> investigated mechanisms leading to brain damage in methylmalonic aciduria. The in vitro model was challenged with the catabolic stress of temperature shift. <a href="#29" class="mim-tip-reference" title="Remacle, N., Forny, P., Cudre-Cung, H.-P., Gonzalez-Melo, M., do Vale-Pereira, S., Henry, H., Teav, T., Gallart-Ayala, H., Braissant, O., Baumgartner, M., Ballhausen, D. <strong>New in vitro model derived from brain-specific Mut-/- mice confirms cerebral ammonium accumulation in methylmalonic aciduria.</strong> Molec. Genet. Metab. 124: 266-277, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29934063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29934063</a>] [<a href="https://doi.org/10.1016/j.ymgme.2018.06.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29934063">Remacle et al. (2018)</a> found typical metabolites for methylmalonic aciduria as well as a massive ammonia increase in the media of mutant mouse brain cultures. Investigation of pathways involved in intracerebral ammonia production revealed increased expression of glutaminase-2 (GLS2; <a href="/entry/606365">606365</a>) and diminished expression of glutamate dehydrogenase-1 (GLUD1; <a href="/entry/138130">138130</a>) in Mut -/- aggregates. Astrocytes showed swollen fibers and cell bodies, and oligodendrocytes showed inhibited axonal elongation and delayed myelination. Most effects were even more pronounced after 48 hours at 39 degrees C. Microglia activation and an increased apoptosis rate suggested degeneration of Mut -/- brain cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29934063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>14 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/609058" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=609058[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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, GLN17TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918248 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918248;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=rs121918248" 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=rs121918248" 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=RCV000001954 OR RCV000203362 OR RCV001376600 OR RCV001553684 OR RCV001831507" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001954, RCV000203362, RCV001376600, RCV001553684, RCV001831507" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001954...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#12" class="mim-tip-reference" title="Fenton, W. A., Hack, A. M., Kraus, J. P., Rosenberg, L. E. <strong>Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import.</strong> Proc. Nat. Acad. Sci. 84: 1421-1424, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2881300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2881300</a>] [<a href="https://doi.org/10.1073/pnas.84.5.1421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2881300">Fenton et al. (1987)</a> identified a mutation in the MUT gene that appeared to represent an amino-terminal deletion that removed the leader peptide necessary for proper uptake and cleavage of the precursor. <a href="#18" class="mim-tip-reference" title="Ledley, F. D., Jansen, R., Nham, S.-U., Fenton, W. A., Rosenberg, L. E. <strong>Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes mut-0 methylmalonic acidemia.</strong> Proc. Nat. Acad. Sci. 87: 3147-3150, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970180</a>] [<a href="https://doi.org/10.1073/pnas.87.8.3147" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1970180">Ledley et al. (1990)</a> identified a C-to-T transition in the MUT gene, resulting in a gln17-to-ter (Q17X) substitution in the mitochondrial leader sequence of the protein as a cause of mut(0) MMA (<a href="/entry/251000">251000</a>). Cells carrying this mutation produced immunoreactive protein translated from AUG codons downstream from the termination codon and, therefore, lack a mitochondrial leader peptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1970180+2881300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, TRP105ARG
|
|
</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> rs121918249 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918249;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/rs121918249?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=rs121918249" 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=rs121918249" 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=RCV000001955 OR RCV000203407 OR RCV000374459 OR RCV001271724 OR RCV003114172" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001955, RCV000203407, RCV000374459, RCV001271724, RCV003114172" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001955...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with mut(0) MMA (<a href="/entry/251000">251000</a>), <a href="#16" class="mim-tip-reference" title="Jansen, R., Ledley, F. D. <strong>Heterozygous mutations at the mut locus in fibroblasts with mut-0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning.</strong> Am. J. Hum. Genet. 47: 808-814, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1977311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1977311</a>]" pmid="1977311">Jansen and Ledley (1990)</a> identified compound heterozygosity for 2 mutations in the MUT gene: a 389T-C transition, resulting in a trp105-to-arg (W105R) substitution, and a 1206C-A transversion, resulting in an ala378-to-glu substitution (A378E; <a href="#0003">609058.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1977311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, ALA378GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918250 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918250;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=rs121918250" 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=rs121918250" 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=RCV000001956 OR RCV002512663" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001956, RCV002512663" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001956...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ala378-to-glu (A378E) mutation in the MUT gene that was found in compound heterozygous state in a patient with mut(0) methylmalonic aciduria (<a href="/entry/251000">251000</a>) by <a href="#16" class="mim-tip-reference" title="Jansen, R., Ledley, F. D. <strong>Heterozygous mutations at the mut locus in fibroblasts with mut-0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning.</strong> Am. J. Hum. Genet. 47: 808-814, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1977311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1977311</a>]" pmid="1977311">Jansen and Ledley (1990)</a>, see <a href="#0002">609058.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1977311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, ARG93HIS
|
|
</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> rs121918251 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918251;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/rs121918251?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=rs121918251" 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=rs121918251" 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=RCV000001957 OR RCV000175568 OR RCV000724019 OR RCV000780493 OR RCV004752675" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001957, RCV000175568, RCV000724019, RCV000780493, RCV004752675" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001957...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In skin fibroblasts derived from a patient with neonatal methylmalonic aciduria (<a href="/entry/251000">251000</a>) who died at the age of 5 months, <a href="#28" class="mim-tip-reference" title="Raff, M. L., Crane, A. M., Jansen, R., Ledley, F. D., Rosenblatt, D. S. <strong>Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut(0) and mut(-) methylmalonic aciduria by interallelic complementation.</strong> J. Clin. Invest. 87: 203-207, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1670635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1670635</a>] [<a href="https://doi.org/10.1172/JCI114972" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1670635">Raff et al. (1991)</a> identified a 354G-A transition in the MUT gene, resulting in an arg93-to-his (R93H) substitution. Cell-fusion complementation analysis showed complementation with 4 out of 5 mut(-) lines and 3 out of 9 mut(0) lines, suggesting interallelic complementation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1670635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Ledley, F. D., Rosenblatt, D. S. <strong>Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations.</strong> Hum. Mutat. 9: 1-6, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990001</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)9:1<1::AID-HUMU1>3.0.CO;2-E" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8990001">Ledley and Rosenblatt (1997)</a> noted most of the MUT mutations that complement R93H are located in a common region near the C terminus of the protein, suggesting that these mutations complement a discrete function required for activity of the R93H protein. Mutations exhibiting complementation with R93H include G623R (<a href="#0008">609058.0008</a>) and G703R (<a href="#0009">609058.0009</a>) among the mut(0) cell lines, and G717V (<a href="#0005">609058.0005</a>) among the mut(-) cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8990001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(-) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, GLY717VAL
|
|
</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> rs121918252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918252;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/rs121918252?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=rs121918252" 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=rs121918252" 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=RCV000001958 OR RCV000078445 OR RCV000174456 OR RCV000781613 OR RCV001276629" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001958, RCV000078445, RCV000174456, RCV000781613, RCV001276629" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001958...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a mut(-) MMA (<a href="/entry/251000">251000</a>) phenotype previously characterized by <a href="#17" class="mim-tip-reference" title="Ledley, F. D., Crane, A. M., Lumetta, M. <strong>Heterogeneous alleles and expression of methylmalonyl CoA mutase in mut methylmalonic acidemia.</strong> Am. J. Hum. Genet. 46: 539-547, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1968706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1968706</a>]" pmid="1968706">Ledley et al. (1990)</a>, <a href="#8" class="mim-tip-reference" title="Crane, A. M., Jansen, R., Andrews, E. R., Ledley, F. D. <strong>Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut(-) methylmalonic aciduria.</strong> J. Clin. Invest. 89: 385-391, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346616</a>] [<a href="https://doi.org/10.1172/JCI115597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1346616">Crane et al. (1992)</a> identified 3 novel base changes in the MUT gene. They concluded that the particular phenotype was due to a homozygous gly717-to-val (G717V) substitution, which resulted in an unstable enzyme. This mutation showed interallelic complementation with the R93H mutation (<a href="#0004">609058.0004</a>). The patient was also homozygous also 2 other mutations which were presumably neutral: his532-to-arg (H532R) and val671-to-ile (V671I). <a href="#10" class="mim-tip-reference" title="Crane, A. M., Martin, L. S., Valle, D., Ledley, F. D. <strong>Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase.</strong> Hum. Genet. 89: 259-264, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1351030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1351030</a>] [<a href="https://doi.org/10.1007/BF00220536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1351030">Crane et al. (1992)</a> compared the phenotype in the original patient and in 2 others with the G717V mutation. All 3 presented in the first years of life with multiple episodes of life-threatening organic acidosis and hyperammonemia. None had evidence of disease in the perinatal period, and all 3 were of low-normal intelligence. The authors concluded that the phenotype was intermediate between the fulminant and benign forms of methylmalonic aciduria, and suggested that the level of residual MUT enzyme activity associated with the G717V mutation may be close to the threshold required in vivo for maintaining metabolic homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1968706+1351030+1346616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 mutation screen of 160 patients with mut MMA, <a href="#34" class="mim-tip-reference" title="Worgan, L. C., Niles, K., Tirone, J. C., Hofmann, A., Verner, A., Sammak, A., Kucic, T., Lepage, P., Rosenblatt, D. S. <strong>Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.</strong> Hum. Mutat. 27: 31-43, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16281286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16281286</a>] [<a href="https://doi.org/10.1002/humu.20258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16281286">Worgan et al. (2006)</a> found the G717V mutation in 12 of 29 black patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16281286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 METHYLMALONIC ACIDURIA, mut(-) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, GLU117TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918253 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918253;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=rs121918253" 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=rs121918253" 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=RCV000001959 OR RCV000670836 OR RCV001384465 OR RCV001826404" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001959, RCV000670836, RCV001384465, RCV001826404" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001959...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#26" class="mim-tip-reference" title="Ogasawara, M., Matsubara, Y., Mikami, H., Narisawa, K. <strong>Identification of two novel mutations in the methylmalonyl-CoA mutase gene with decreased levels of mutant mRNA in methylmalonic acidemia.</strong> Hum. Molec. Genet. 3: 867-872, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951229</a>] [<a href="https://doi.org/10.1093/hmg/3.6.867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951229">Ogasawara et al. (1994)</a> identified 2 novel mutations in the MUT gene, 1 of which was prevalent among Japanese patients with mut(-) MMA (<a href="/entry/251000">251000</a>). One patient was homozygous for a 425G-T transversion resulting in a glu117-to-ter (E117X) substitution. The E117X mutation was accompanied by instability of MCM mRNA, the first report of such a mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951229" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(-) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, 2-BP DEL, 769CA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2127419920 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2127419920;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=rs2127419920" 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=rs2127419920" 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=RCV000001960" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001960" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001960</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with MMA mut(-) (<a href="/entry/251000">251000</a>), <a href="#26" class="mim-tip-reference" title="Ogasawara, M., Matsubara, Y., Mikami, H., Narisawa, K. <strong>Identification of two novel mutations in the methylmalonyl-CoA mutase gene with decreased levels of mutant mRNA in methylmalonic acidemia.</strong> Hum. Molec. Genet. 3: 867-872, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951229</a>] [<a href="https://doi.org/10.1093/hmg/3.6.867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951229">Ogasawara et al. (1994)</a> found compound heterozygosity for 2 mutations in the MUT gene: the E117X mutation (<a href="#0006">609058.0006</a>) frequent in Japanese patients and a 2-bp deletion (769delCA), resulting in a frameshift and premature termination. The termination occurred 508 amino acids upstream of the C-terminus of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951229" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, GLY623ARG
|
|
</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> rs121918254 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918254;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/rs121918254?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=rs121918254" 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=rs121918254" 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=RCV000001961 OR RCV000203390 OR RCV000427444 OR RCV001276633 OR RCV002271364 OR RCV004752676" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001961, RCV000203390, RCV000427444, RCV001276633, RCV002271364, RCV004752676" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001961...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an African American male infant with MMA mut(0) (<a href="/entry/251000">251000</a>), <a href="#27" class="mim-tip-reference" title="Qureshi, A. A., Crane, A. M., Matiaszuk, N. V., Rezvani, I., Ledley, F. D., Rosenblatt, D. S. <strong>Cloning and expression of mutations demonstrating intragenic complementation in mut-0 methylmalonic aciduria.</strong> J. Clin. Invest. 93: 1812-1819, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7909321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7909321</a>] [<a href="https://doi.org/10.1172/JCI117166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7909321">Qureshi et al. (1994)</a> identified compound heterozygosity for 2 mutations in the MUT gene: gly623-to-arg (G623R) and gly703-to-arg (G703R; <a href="#0009">609058.0009</a>). Cotransfection of each mutation with the R93H mutation mutation (<a href="#0004">609058.0004</a>) stimulated propionate uptake, indicating that both mutations were independently capable of complementing the R93H mutation, whereas the G717V mutation (<a href="#0005">609058.0005</a>) did not complement the G623R cell line. <a href="#27" class="mim-tip-reference" title="Qureshi, A. A., Crane, A. M., Matiaszuk, N. V., Rezvani, I., Ledley, F. D., Rosenblatt, D. S. <strong>Cloning and expression of mutations demonstrating intragenic complementation in mut-0 methylmalonic aciduria.</strong> J. Clin. Invest. 93: 1812-1819, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7909321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7909321</a>] [<a href="https://doi.org/10.1172/JCI117166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7909321">Qureshi et al. (1994)</a> found that the MUT mutations identified in cell lines that exhibit intragenic complementation to G623R do not exhibit any specific pattern of charge or amino acid structure. Furthermore, neither the mut(0) versus mut(-) phenotype nor intragenic complementation could be predicted by the relative primary amino acid position. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7909321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, GLY703ARG
|
|
</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> rs121918255 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918255;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/rs121918255?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=rs121918255" 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=rs121918255" 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=RCV000001962 OR RCV005089146" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001962, RCV005089146" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001962...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gly703-to-arg (G703R) mutation in the MUT gene that was found in compound heterozygous state in a patient with mut(0) methylmalonic aciduria (<a href="/entry/251000">251000</a>) by <a href="#27" class="mim-tip-reference" title="Qureshi, A. A., Crane, A. M., Matiaszuk, N. V., Rezvani, I., Ledley, F. D., Rosenblatt, D. S. <strong>Cloning and expression of mutations demonstrating intragenic complementation in mut-0 methylmalonic aciduria.</strong> J. Clin. Invest. 93: 1812-1819, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7909321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7909321</a>] [<a href="https://doi.org/10.1172/JCI117166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7909321">Qureshi et al. (1994)</a>, see <a href="#0008">609058.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7909321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, ASN219TYR
|
|
</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> rs121918256 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918256;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/rs121918256?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=rs121918256" 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=rs121918256" 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=RCV000001963 OR RCV000186055 OR RCV000203309 OR RCV000587363 OR RCV001271716" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001963, RCV000186055, RCV000203309, RCV000587363, RCV001271716" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001963...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 unrelated patients with MMA mut(0) (<a href="/entry/251000">251000</a>), <a href="#1" class="mim-tip-reference" title="Acquaviva, C., Benoist, J.-F., Callebaut, I., Guffon, N., Ogier de Baulny, H., Touati, G., Aydin, A., Porquet, D., Elion, J. <strong>N219Y, a new frequent mutation among mut-0 forms of methylmalonic acidemia in Caucasian patients.</strong> Europ. J. Hum. Genet. 9: 577-582, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11528502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11528502</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11528502">Acquaviva et al. (2001)</a> identified a 731A-T transversion in the MUT gene, resulting in an asn219-to-tyr (N219Y)in a conserved codon from bacteria to mouse and man. Mapping of the mutation onto a 3-dimensional model of human MCM suggested impaired folding and/or poor stability compatible with the mut(0) phenotype. Functional expression studies showed loss of enzyme activity. Three of the patients were homozygous for the N219Y mutation and 2 patients were compound heterozygous. The 5 patients were of French or Turkish descent, from a population of 19 patients with MCM apoenzyme deficiency, and the N219Y mutation represented 21% of the MUT alleles screened. Further screening for this mutation in 205 French children revealed 2 carriers, suggesting that N219Y is a frequent mutation in the French population and that the incidence of MMA might be underestimated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11528502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The high frequency of N219Y in Caucasians was confirmed by the study of <a href="#2" class="mim-tip-reference" title="Acquaviva, C., Benoist, J.-F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D., Elion, J. <strong>Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(0) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.</strong> Hum. Mutat. 25: 167-176, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15643616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15643616</a>] [<a href="https://doi.org/10.1002/humu.20128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15643616">Acquaviva et al. (2005)</a>, who found that this allele represented 19% of the alleles tested among 40 European patients. <a href="#4" class="mim-tip-reference" title="Berger, I., Shaag, A., Anikster, Y., Baumgartner, E. R., Bar-Meir, M., Joseph, A., Elpeleg, O. N. <strong>Mutation analysis of the MCM gene in Israeli patients with mut(0) disease.</strong> Molec. Genet. Metab. 73: 107-110, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11350191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11350191</a>] [<a href="https://doi.org/10.1006/mgme.2001.3166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11350191">Berger et al. (2001)</a> detected the N219Y mutation in homozygous state in 2 of 7 Arab Muslim patients, suggesting that this mutation may also be frequent in this ethnic group. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15643616+11350191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, ARG108CYS
|
|
</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> rs121918257 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918257;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/rs121918257?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=rs121918257" 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=rs121918257" 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=RCV000001964 OR RCV000197802 OR RCV000203340 OR RCV001192656 OR RCV001271723 OR RCV001376644 OR RCV004018538 OR RCV004752677" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001964, RCV000197802, RCV000203340, RCV001192656, RCV001271723, RCV001376644, RCV004018538, RCV004752677" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001964...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a screen of the MUT gene in 160 patients with mut MMA (<a href="/entry/251000">251000</a>), <a href="#34" class="mim-tip-reference" title="Worgan, L. C., Niles, K., Tirone, J. C., Hofmann, A., Verner, A., Sammak, A., Kucic, T., Lepage, P., Rosenblatt, D. S. <strong>Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.</strong> Hum. Mutat. 27: 31-43, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16281286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16281286</a>] [<a href="https://doi.org/10.1002/humu.20258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16281286">Worgan et al. (2006)</a> found a novel mutation in exon 2, 322C-T (arg108 to cys, R108C), in 16 of 27 Hispanic patients. SNP phenotyping data demonstrated that Hispanic patients with this mutation shared a common haplotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16281286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, GLY215SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918258 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918258;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=rs121918258" 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=rs121918258" 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=RCV000001965 OR RCV000203381 OR RCV001851570" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001965, RCV000203381, RCV001851570" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001965...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#6" class="mim-tip-reference" title="Cavicchi, C., Donati, M. A., Funghini, S., la Marca, G., Malvagia, S., Ciani, F., Poggi, G. M., Pasquini, E., Zammarchi, E., Morrone, A. <strong>Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria.</strong> Clin. Genet. 69: 72-76, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16451139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16451139</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00547.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16451139">Cavicchi et al. (2006)</a> performed genetic and biochemical prenatal diagnosis at 11 weeks' gestation in a family with a proband affected by MMA (<a href="/entry/251000">251000</a>) due to homozygosity for a 643G-A transition in the MUT gene resulting in a gly215-to-ser substitution (G215S). Both chorionic villus and amniotic fluid samples were used. The presence of high levels of methylmalonic acid and propionylcarnitine determined by gas chromatography/mass spectrometry and tandem mass spectrometry analysis, respectively, and the identification of the G215S mutation in homozygosity in fetal DNA allowed a certain, rapid, and early diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16451139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, IVS11, C-A, -891
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1581819081 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1581819081;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=rs1581819081" 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=rs1581819081" 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=RCV000001966" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001966" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001966</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> studied a patient with mut MMA (<a href="/entry/251000">251000</a>) who had been found by <a href="#24" class="mim-tip-reference" title="Martinez, M. A., Rincon, A., Desviat, L. R., Merinero, B., Ugarte, M., Perez, B. <strong>Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.</strong> Molec. Genet. Metab. 84: 317-325, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781192</a>] [<a href="https://doi.org/10.1016/j.ymgme.2004.11.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781192">Martinez et al. (2005)</a> to have a 76-bp insertion between exons 11 and 12 corresponding to an exon-like region in intron 11 (1957ins76). <a href="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> found that the patient's DNA contained a C-to-A change in intron 11 at position +7 relative to the inserted sequence (IVS11-891C-A). Experimental confirmation that the change was pathogenic and caused the activation of the pseudoexon was obtained by use of a minigene. <a href="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> used antisense morpholino oligonucleotides (AMOs) to target a cryptic splice site to block access of the splicing machinery in the pseudoexonic region in the pre-mRNA. Using this antisense therapeutics, they obtained correctly spliced mRNA that was effectively translated, and methylmalonyl CoA mutase (MCM) activity was rescued in the patients' fibroblasts. The effect of the AMO was sequence- and dose-dependent. Close to 100% of MCM activity, measured by incorporation of (14)C-propionate, was obtained after 48 hours, and correctly spliced MUT mRNA was still detected 15 days after treatment. The patient with MUT deficiency studied by <a href="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> was compound heterozygous for the intronic insertion and a splicing mutation in the last nucleotide of exon 10 (1808G-A; <a href="#0014">609058.0014</a>), and had 2 aberrant transcripts as a result of the use of cryptic splice sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15781192+17966092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MMUT, 1808G-A
|
|
</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> rs1412463565 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1412463565;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/rs1412463565?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=rs1412463565" 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=rs1412463565" 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=RCV000001967 OR RCV003555894" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001967, RCV003555894" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001967...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the splice site mutation in the MUT gene (1808G-A) that was found in compound heterozygous state in a patient with mut MMA (<a href="/entry/251000">251000</a>) by <a href="#30" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a>, see <a href="#0013">609058.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17966092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Ledley1990" class="mim-tip-reference" title="Ledley, F. D. <strong>Perspectives on methylmalonic acidemia resulting from molecular cloning of methylmalonyl CoA mutase.</strong> BioEssays 12: 335-340, 1990.">Ledley (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="Acquaviva2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Acquaviva, C., Benoist, J.-F., Callebaut, I., Guffon, N., Ogier de Baulny, H., Touati, G., Aydin, A., Porquet, D., Elion, J.
|
|
<strong>N219Y, a new frequent mutation among mut-0 forms of methylmalonic acidemia in Caucasian patients.</strong>
|
|
Europ. J. Hum. Genet. 9: 577-582, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11528502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11528502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11528502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200675" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Acquaviva2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Acquaviva, C., Benoist, J.-F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D., Elion, J.
|
|
<strong>Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(0) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.</strong>
|
|
Hum. Mutat. 25: 167-176, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15643616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15643616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15643616" target="_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.20128" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Adjalla1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Adjalla, C. E., Hosack, A. R., Gilfix, B. M., Lamothe, E., Sun, S., Chan, A., Evans, S., Matiaszuk, N. V., Rosenblatt, D. S.
|
|
<strong>Seven novel mutations in mut methylmalonic aciduria.</strong>
|
|
Hum. Mutat. 11: 270-274, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554742" target="_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(1998)11:4<270::AID-HUMU3>3.0.CO;2-T" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Berger2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berger, I., Shaag, A., Anikster, Y., Baumgartner, E. R., Bar-Meir, M., Joseph, A., Elpeleg, O. N.
|
|
<strong>Mutation analysis of the MCM gene in Israeli patients with mut(0) disease.</strong>
|
|
Molec. Genet. Metab. 73: 107-110, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11350191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11350191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11350191" target="_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/mgme.2001.3166" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Blanche1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blanche, H., Zoghbi, H. Y., Jabs, E. W., de Gouyon, B., Zunec, R., Dausset, J., Cann, H. M.
|
|
<strong>A centromere-based genetic map of the short arm of human chromosome 6.</strong>
|
|
Genomics 9: 420-428, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2032717/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2032717</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2032717" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90407-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Cavicchi2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cavicchi, C., Donati, M. A., Funghini, S., la Marca, G., Malvagia, S., Ciani, F., Poggi, G. M., Pasquini, E., Zammarchi, E., Morrone, A.
|
|
<strong>Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria.</strong>
|
|
Clin. Genet. 69: 72-76, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16451139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16451139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16451139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2005.00547.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Champattanachai2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Champattanachai, V., Ketudat Cairns, J. R., Shotelersuk, V., Keeratichamroen, S., Sawangareetrakul, P., Srisomsap, C., Kaewpaluek, V., Svasti, J.
|
|
<strong>Novel mutations in a Thai patient with methylmalonic acidemia.</strong>
|
|
Molec. Genet. Metab. 79: 300-302, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12948746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12948746</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12948746" target="_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/s1096-7192(03)00106-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Crane1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crane, A. M., Jansen, R., Andrews, E. R., Ledley, F. D.
|
|
<strong>Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut(-) methylmalonic aciduria.</strong>
|
|
J. Clin. Invest. 89: 385-391, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115597" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Crane1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crane, A. M., Ledley, F. D.
|
|
<strong>Clustering of mutations in methylmalonyl CoA mutase associated with mut(-) methylmalonic acidemia.</strong>
|
|
Am. J. Hum. Genet. 55: 42-50, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7912889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7912889</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7912889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Crane1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crane, A. M., Martin, L. S., Valle, D., Ledley, F. D.
|
|
<strong>Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase.</strong>
|
|
Hum. Genet. 89: 259-264, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1351030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1351030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1351030" target="_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/BF00220536" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Drennan1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Drennan, C. L., Matthews, R. G., Rosenblatt, D. S., Ledley, F. D., Fenton, W. A., Ludwig, M. L.
|
|
<strong>Molecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: deductions from the structure of methionine synthase.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 5550-5555, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8643613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8643613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8643613" target="_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.93.11.5550" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Fenton1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fenton, W. A., Hack, A. M., Kraus, J. P., Rosenberg, L. E.
|
|
<strong>Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 1421-1424, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2881300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2881300</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2881300" target="_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.84.5.1421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Forny2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Forny, P., Froese, D. S., Suormala, T., Yue, W. W., Baumgartner, M. R.
|
|
<strong>Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.</strong>
|
|
Hum. Mutat. 35: 1449-1458, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25125334[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=25125334" target="_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.22633" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Janata1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janata, J., Kogekar, N., Fenton, W. A.
|
|
<strong>Expression and kinetic characterization of methylmalonyl-CoA mutase from patients with the mut- phenotype: evidence for naturally occurring interallelic complementation.</strong>
|
|
Hum. Molec. Genet. 6: 1457-1464, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285782" target="_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/6.9.1457" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Jansen1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jansen, R., Kalousek, F., Fenton, W. A., Rosenberg, L. E., Ledley, F. D.
|
|
<strong>Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction.</strong>
|
|
Genomics 4: 198-205, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2567699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2567699</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2567699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(89)90300-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Jansen1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jansen, R., Ledley, F. D.
|
|
<strong>Heterozygous mutations at the mut locus in fibroblasts with mut-0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning.</strong>
|
|
Am. J. Hum. Genet. 47: 808-814, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1977311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1977311</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1977311" 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="Ledley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Crane, A. M., Lumetta, M.
|
|
<strong>Heterogeneous alleles and expression of methylmalonyl CoA mutase in mut methylmalonic acidemia.</strong>
|
|
Am. J. Hum. Genet. 46: 539-547, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1968706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1968706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1968706" 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="Ledley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Jansen, R., Nham, S.-U., Fenton, W. A., Rosenberg, L. E.
|
|
<strong>Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes mut-0 methylmalonic acidemia.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 3147-3150, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1970180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.87.8.3147" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Ledley1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Lumetta, M., Nguyen, P. N., Kolhouse, J. F., Allen, R. H.
|
|
<strong>Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut cell lines.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 3518-3521, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2453061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2453061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2453061" target="_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.85.10.3518" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Ledley1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Lumetta, M. R., Zoghbi, H. Y., vanTuinen, P., Ledbetter, S. A., Ledbetter, D. H.
|
|
<strong>Mapping of human methylmalonyl CoA mutase (MUT) locus on chromosome 6.</strong>
|
|
Am. J. Hum. Genet. 42: 839-846, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2897160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2897160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2897160" 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="21" class="mim-anchor"></a>
|
|
<a id="Ledley1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Rosenblatt, D. S.
|
|
<strong>Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations.</strong>
|
|
Hum. Mutat. 9: 1-6, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990001</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8990001" target="_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)9:1<1::AID-HUMU1>3.0.CO;2-E" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Ledley1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., vanTuinen, P., Ledbetter, S. A., Ledbetter, D.
|
|
<strong>Assignment of methylmalonyl CoA mutase locus to human chromosome 6. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 646 only, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Ledley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ledley, F. D.
|
|
<strong>Perspectives on methylmalonic acidemia resulting from molecular cloning of methylmalonyl CoA mutase.</strong>
|
|
BioEssays 12: 335-340, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1975493" target="_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/bies.950120706" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Martinez2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martinez, M. A., Rincon, A., Desviat, L. R., Merinero, B., Ugarte, M., Perez, B.
|
|
<strong>Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.</strong>
|
|
Molec. Genet. Metab. 84: 317-325, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781192</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2004.11.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Nham1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nham, S.-U., Wilkemeyer, M. F., Ledley, F. D.
|
|
<strong>Structure of the human methylmalonyl-CoA mutase (MUT) locus.</strong>
|
|
Genomics 8: 710-716, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1980486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1980486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1980486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90259-w" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Ogasawara1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ogasawara, M., Matsubara, Y., Mikami, H., Narisawa, K.
|
|
<strong>Identification of two novel mutations in the methylmalonyl-CoA mutase gene with decreased levels of mutant mRNA in methylmalonic acidemia.</strong>
|
|
Hum. Molec. Genet. 3: 867-872, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951229</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951229" target="_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/3.6.867" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Qureshi1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Qureshi, A. A., Crane, A. M., Matiaszuk, N. V., Rezvani, I., Ledley, F. D., Rosenblatt, D. S.
|
|
<strong>Cloning and expression of mutations demonstrating intragenic complementation in mut-0 methylmalonic aciduria.</strong>
|
|
J. Clin. Invest. 93: 1812-1819, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7909321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7909321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7909321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI117166" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Raff1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raff, M. L., Crane, A. M., Jansen, R., Ledley, F. D., Rosenblatt, D. S.
|
|
<strong>Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut(0) and mut(-) methylmalonic aciduria by interallelic complementation.</strong>
|
|
J. Clin. Invest. 87: 203-207, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1670635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1670635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1670635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI114972" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Remacle2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Remacle, N., Forny, P., Cudre-Cung, H.-P., Gonzalez-Melo, M., do Vale-Pereira, S., Henry, H., Teav, T., Gallart-Ayala, H., Braissant, O., Baumgartner, M., Ballhausen, D.
|
|
<strong>New in vitro model derived from brain-specific Mut-/- mice confirms cerebral ammonium accumulation in methylmalonic aciduria.</strong>
|
|
Molec. Genet. Metab. 124: 266-277, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29934063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29934063</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29934063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2018.06.008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Rincon2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B.
|
|
<strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong>
|
|
Am. J. Hum. Genet. 81: 1262-1270, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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=17966092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/522376" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Sertic1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sertic, J., Vincek, V., Ledley, F. D., Figueroa, F., Klein, J.
|
|
<strong>Mapping of the L-methylmalonyl-CoA mutase gene to mouse chromosome 17.</strong>
|
|
Genomics 6: 560-564, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970332</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1970332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90487-f" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Takeshima2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeshima, Y., Yagi, M., Wada, H., Ishibashi, K., Nishiyama, A., Kakumoto, M., Sakaeda, T., Saura, R., Okumura, K., Matsuo, M.
|
|
<strong>Intravenous infusion of an antisense oligonucleotide results in exon skipping in muscle dystrophin mRNA of Duchenne muscular dystrophy.</strong>
|
|
Pediat. Res. 59: 690-694, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16627883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16627883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16627883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/01.pdr.0000215047.51278.7c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Threadgill1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Threadgill, D. W., Wilkemeyer, M., Womack, J. E., Ledley, F. D.
|
|
<strong>Localization of the murine methylmalonyl CoA mutase (Mut) locus on chromosome 17 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 53: 112-114, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1973376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1973376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1973376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000132907" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Worgan2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Worgan, L. C., Niles, K., Tirone, J. C., Hofmann, A., Verner, A., Sammak, A., Kucic, T., Lepage, P., Rosenblatt, D. S.
|
|
<strong>Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.</strong>
|
|
Hum. Mutat. 27: 31-43, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16281286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16281286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16281286" target="_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.20258" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Zoghbi1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zoghbi, H. Y., O'Brien, W. E., Ledley, F. D.
|
|
<strong>Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6.</strong>
|
|
Genomics 3: 396-398, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2907507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(88)90135-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Hilary J. Vernon - updated : 01/14/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 12/07/2018<br>Victor A. McKusick - updated : 11/28/2007<br>Victor A. McKusick - updated : 3/7/2006<br>Victor A. McKusick - updated : 1/20/2006<br>Victor A. McKusick - updated : 3/7/2005<br>Cassandra L. Kniffin - updated : 12/6/2004
|
|
</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">
|
|
Cassandra L. Kniffin : 12/1/2004
|
|
</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 : 01/08/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 06/14/2022<br>carol : 01/14/2022<br>carol : 12/20/2021<br>carol : 02/26/2020<br>alopez : 12/07/2018<br>alopez : 07/22/2015<br>mcolton : 6/26/2015<br>carol : 3/28/2013<br>terry : 5/31/2011<br>wwang : 5/12/2011<br>alopez : 12/11/2007<br>alopez : 12/11/2007<br>alopez : 12/11/2007<br>terry : 11/28/2007<br>terry : 11/16/2006<br>alopez : 3/14/2006<br>alopez : 3/14/2006<br>terry : 3/7/2006<br>alopez : 2/15/2006<br>terry : 1/20/2006<br>terry : 4/21/2005<br>carol : 4/5/2005<br>tkritzer : 3/14/2005<br>terry : 3/7/2005<br>carol : 12/10/2004<br>ckniffin : 12/6/2004
|
|
</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> 609058
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
METHYLMALONYL-CoA MUTASE; MMUT
|
|
|
|
</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">
|
|
MUT<br />
|
|
METHYLMALONYL-CoA ISOMERASE<br />
|
|
MCM
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: MMUT</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 6p12.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 6:49,430,360-49,463,253 </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">
|
|
6p12.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Methylmalonic aciduria, mut(0) type
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
251000
|
|
</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>Methylmalonyl-CoA mutase (MUT) (EC 5.4.99.2) is a mitochondrial enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. MUT activity requires 5-prime-deoxyadenosylcobalamin (AdoCbl), a coenzyme form of vitamin B12.</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>By screening human placenta and liver cDNA libraries with an anti-MCM antibody, Ledley et al. (1988) isolated a partial MUT cDNA. </p><p>Jansen et al. (1989) isolated a full-length cDNA corresponding to the MUT gene from a human liver cDNA library. The deduced 742-amino acid protein has a molecular mass of 82.2 kD; the mature protein is 78.5 kD. The mitochondrial leader sequence comprises 32 amino acids. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Nham et al. (1990) determined that the MUT gene contains 13 exons spanning more than 35 kb. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ledley et al. (1987) assigned the methylmalonyl-CoA mutase locus to chromosome 6p by use of a full-length MCM cDNA clone from a human liver cDNA library. By Southern blot analysis of DNA from human-hamster somatic cell hybrid cell lines, Ledley et al. (1988) assigned the MUT locus to 6p23-q12. By in situ hybridization, the locus was further localized to 6p21.2-p12. A highly informative RFLP was identified at the MCM gene locus. </p><p>By deletion mapping in cell lines with 6p deletions, Zoghbi et al. (1988) demonstrated that the MUT gene is located on 6p, proximal to GLO1 (138750). By use of a HindIII polymorphism identified by the MUT cDNA, they demonstrated the linkage relationships to HLA in reference CEPH families; the maximum lod score for MUT versus HLA was 3.04 at a recombination fraction of 0.28. Blanche et al. (1991) presented a genetic map of 6p which included RFLP mapping of the MUT locus. </p><p>By a study of recombinant inbred and congenic strains, Sertic et al. (1990) demonstrated that the mouse equivalent of the MUT gene is located on chromosome 17. Threadgill et al. (1990) assigned the gene to mouse chromosome 17 by in situ hybridization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ledley et al. (1990) could demonstrate no gross abnormalities of the MCM gene by Southern blot analysis in cell lines from patients with methylmalonic acidemia (MMA; see 251000). By other methods, however, they concluded that there are several independent alleles giving different levels of mRNA expression and biochemical phenotype of the cultured cells. The studies provided a molecular explanation for the wide phenotypic spectrum observed in the disorder. </p><p>In a patient with MMA mut(0), defined as having no residual enzyme activity, Jansen and Ledley (1990) identified compound heterozygosity for 2 mutations in the MUT gene (609058.0001 and 609058.0002). </p><p>In a patient with MMA mut(-), defined as having some residual enzyme activity, who had been reported by Ledley et al. (1990), Crane et al. (1992) identified a homozygous mutation in the MUT gene (609058.0005). </p><p>Crane and Ledley (1994) identified 4 novel mutations clustered near the C terminus of the MUT protein in patients with MMA. Three of the patients responded to cobalamin therapy. Each mutation showed interallelic complementation in cotransfection assays with clones bearing an R93H mutation (609058.0004). The findings suggested that the C-terminal region of the protein represents a cobalamin-binding domain. The location of this domain, as well as a pattern of sequence preservation between the homologous human and Propionobacterium shermanii enzymes, suggested a mechanism for interallelic complementation in which the cobalamin-binding defect is complemented in trans from the heterologous subunits of the dimer. </p><p>Drennan et al. (1996) made deductions concerning the molecular basis for dysfunction of some mutant forms of MCM by aligning the sequence of this gene with that of other B12-dependent enzymes, including the C-terminal portion of the cobalamin-binding region of methionine synthase (156570) from E. coli, the structure of which had been determined by x-ray crystallography. Previously identified mutants such as gly623-to-arg (609058.0008) were predicted to interfere with the structure and/or stability of the loop that carries histidine-627, the presumed lower axial ligand to the cobalt of adenosylcobalamin. A mutant such as gly703-to-arg (609058.0009), which maps to the binding site for the dimethylbenzimidazole nucleotide substituent of adenosylcobalamin, was predicted to block the binding of adenosylcobalamin because of the substitution of a large amino acid side chain for glycine. </p><p>Janata et al. (1997) identified 6 missense mutations producing amino acid changes in MUT cDNA from patients with mut(-) MMA. Two of the mutations had been reported in other patients. In 1 cell line, which the authors referred to as doubly heterozygous (compound heterozygous is the correct description), expression studies indicated that neither of the constituent mutant enzymes had a Km corresponding to the lower of the 2 estimated from the extract data. The finding was thought to reflect the natural occurrence of interallelic complementation in vivo in this cell line. </p><p>Adjalla et al. (1998) identified 7 novel mutations in mut methylmalonic aciduria and noted that 23 mutations had previously been identified. </p><p>Acquaviva et al. (2001) reported a novel MUT missense mutation, asn219 to tyr (N219Y; 609058.0010), in 5 unrelated families of French and Turkish descent from a population of 19 patients with MCM apoenzyme deficiency. All the patients exhibited a severe mut(0) methylmalonic acidemia phenotype, and 3 of them were homozygous for the N219Y mutation. The findings represented the first frequent MUT mutation reported in the Caucasian population. </p><p>Champattanachai et al. (2003) reported 2 novel mutations in a Thai patient with mut(0) methylmalonic acidemia. </p><p>Acquaviva et al. (2005) analyzed a cohort of 40 MCM-deficient patients with MMA affected by either the mut(0) or mut(-) form of the disease. By direct sequencing of cDNA and genomic DNA of the MUT gene, they detected 42 mutations, 29 of which were novel. These included 5 frameshift mutations (insertion, deletion, or duplication of a single nucleotide), 5 sequence modifications in consensus splice sites, 6 nonsense and 12 missense mutations, and a large genomic deletion including exon 12. They explored how the 12 novel missense mutations might cause the observed phenotype by mapping them onto a 3-dimensional model of the human MCM generated by homology with the enzyme in P. shermanii. Acquaviva et al. (2005) increased the number of mutations in the MUT gene to 84 and discussed their prevalence and distribution throughout the coding sequence in relation to enzyme structure. The authors noted that most of the mutations in the MUT gene are private, with no demonstrated hotspots. Prior to their study only 2 recurrent mutations had been described: glu 117 to ter (E117X; 609058.0006) and N219Y, which had high frequencies in Japanese and Caucasian populations, respectively. Acquaviva et al. (2005) confirmed a high frequency of N219Y in Caucasians: 12 of their 40 patients carried the mutation in a heterozygous or homozygous state, which represented 19% of the alleles tested. </p><p>Worgan et al. (2006) sequenced the MUT gene in 160 patients with mut MMA. Mutations were identified in 96% of disease alleles. Mutations were distributed through all coding exons, but predominantly in exons 2, 3, 6, and 11. A total of 116 different mutations, 68 of which were novel, were identified; 53% were missense mutations, 22% deletions, duplications or insertions, 16% were nonsense mutations, and 9% were splice site mutations. Sixty-one of the mutations were identified in only 1 family. A novel mutation in exon 2, R108C (609058.0011), was identified in 16 of 27 Hispanic patients. SNP genotyping data demonstrated that Hispanic patients with this mutation shared a common haplotype. Three other mutations were seen exclusively in Hispanic patients. Seven mutations were seen almost exclusively in black patients, including the G717V mutation (609058.0005), which was identified in 12 of 29 black patients. Two mutations were seen only in Asian patients. Some frequently identified mutations were not population-specific and were identified in patients of various ethnic backgrounds. Some of these mutations were found in mutation clusters in exons 2, 3, 6, and 11, suggesting that they represented recurrent mutations. </p><p>Rincon et al. (2007) described 3 genomic alterations--1 in the MUT gene, 1 in the PCCA gene (232000), and 1 in the PCCB gene (232050)--that were responsible for aberrant insertion of intronic sequences in patients' mRNA. The authors targeted the aberrant intronic pseudoexons with antisense morpholino oligonucleotides (AMOs) that prevented aberrant splicing, thus generating normal mRNA which was translated into functional protein, achieving therapeutic correction of the defect in methylmalonic acidemia (251000) or propionic acidemia (606054). No effect on MCM activity was obtained after AMO treatment in cell lines bearing different mutations and exhibiting some levels of intronic MUT insertions. Rincon et al. (2007) suggested that this therapeutic strategy would be potentially applicable to a large number of cases with deep intronic changes that remained undetected by standard mutation-detection techniques at that time. The major issues facing clinical applications of morpholino analogs of oligonucleotides concerned safe delivery and optimal dose determination for each tissue involved. Efficient and nontoxic delivery of AMO to the liver, which would be the target tissue in this disorder, was one major challenge to be overcome before the practical use of AMO in patients with methylmalonic acidemia could be envisaged. In Duchenne muscular dystrophy (310200), antisense oligonucleotides have been administered intravenously, achieving splicing modulation to restore the coding frame for dystrophin (Takeshima et al., 2006). The efficacy of antisense therapeutics for splicing correction must be determined in each disease model and for each deleterious splicing event. </p><p>To understand the pathologic mechanisms leading to MMA, Forny et al. (2014) assessed stability and enzymatic effects of 23 MMUT missense mutations expressed in 2 recombinant expression systems. All 23 mutants had decreased enzymatic function. Stability was assessed based on thermolability and folding of the mutant protein. Six mutations led to abnormal folding, and 4 others led to increased thermolability. In evaluating enzymatic defects in the MMUT mutants, 4 mutations led to isolated Km defects, and 6 mutations led to isolated catalytic defects. Three mutations led to increased Km and thermolability, 1 mutation led to catalytic dysfunction and thermolability, and 3 mutations led to both folding and catalytic defects. Forny et al. (2014) then tested whether osmolytes could stabilize the mutant proteins and found that soluble protein yield was increased with glycerol or TMAO in some mutants. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using 3D organotypic brain cell cultures derived from embryos of a brain-specific Mut -/- mouse, Remacle et al. (2018) investigated mechanisms leading to brain damage in methylmalonic aciduria. The in vitro model was challenged with the catabolic stress of temperature shift. Remacle et al. (2018) found typical metabolites for methylmalonic aciduria as well as a massive ammonia increase in the media of mutant mouse brain cultures. Investigation of pathways involved in intracerebral ammonia production revealed increased expression of glutaminase-2 (GLS2; 606365) and diminished expression of glutamate dehydrogenase-1 (GLUD1; 138130) in Mut -/- aggregates. Astrocytes showed swollen fibers and cell bodies, and oligodendrocytes showed inhibited axonal elongation and delayed myelination. Most effects were even more pronounced after 48 hours at 39 degrees C. Microglia activation and an increased apoptosis rate suggested degeneration of Mut -/- brain cells. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>14 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, GLN17TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918248,
|
|
|
|
|
|
|
|
ClinVar: RCV000001954, RCV000203362, RCV001376600, RCV001553684, RCV001831507
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Fenton et al. (1987) identified a mutation in the MUT gene that appeared to represent an amino-terminal deletion that removed the leader peptide necessary for proper uptake and cleavage of the precursor. Ledley et al. (1990) identified a C-to-T transition in the MUT gene, resulting in a gln17-to-ter (Q17X) substitution in the mitochondrial leader sequence of the protein as a cause of mut(0) MMA (251000). Cells carrying this mutation produced immunoreactive protein translated from AUG codons downstream from the termination codon and, therefore, lack a mitochondrial leader peptide. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, TRP105ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918249,
|
|
|
|
|
|
gnomAD: rs121918249,
|
|
|
|
|
|
ClinVar: RCV000001955, RCV000203407, RCV000374459, RCV001271724, RCV003114172
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with mut(0) MMA (251000), Jansen and Ledley (1990) identified compound heterozygosity for 2 mutations in the MUT gene: a 389T-C transition, resulting in a trp105-to-arg (W105R) substitution, and a 1206C-A transversion, resulting in an ala378-to-glu substitution (A378E; 609058.0003). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, ALA378GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918250,
|
|
|
|
|
|
|
|
ClinVar: RCV000001956, RCV002512663
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ala378-to-glu (A378E) mutation in the MUT gene that was found in compound heterozygous state in a patient with mut(0) methylmalonic aciduria (251000) by Jansen and Ledley (1990), see 609058.0002. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, ARG93HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918251,
|
|
|
|
|
|
gnomAD: rs121918251,
|
|
|
|
|
|
ClinVar: RCV000001957, RCV000175568, RCV000724019, RCV000780493, RCV004752675
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In skin fibroblasts derived from a patient with neonatal methylmalonic aciduria (251000) who died at the age of 5 months, Raff et al. (1991) identified a 354G-A transition in the MUT gene, resulting in an arg93-to-his (R93H) substitution. Cell-fusion complementation analysis showed complementation with 4 out of 5 mut(-) lines and 3 out of 9 mut(0) lines, suggesting interallelic complementation. </p><p>Ledley and Rosenblatt (1997) noted most of the MUT mutations that complement R93H are located in a common region near the C terminus of the protein, suggesting that these mutations complement a discrete function required for activity of the R93H protein. Mutations exhibiting complementation with R93H include G623R (609058.0008) and G703R (609058.0009) among the mut(0) cell lines, and G717V (609058.0005) among the mut(-) cell lines. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 METHYLMALONIC ACIDURIA, mut(-) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, GLY717VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918252,
|
|
|
|
|
|
gnomAD: rs121918252,
|
|
|
|
|
|
ClinVar: RCV000001958, RCV000078445, RCV000174456, RCV000781613, RCV001276629
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a mut(-) MMA (251000) phenotype previously characterized by Ledley et al. (1990), Crane et al. (1992) identified 3 novel base changes in the MUT gene. They concluded that the particular phenotype was due to a homozygous gly717-to-val (G717V) substitution, which resulted in an unstable enzyme. This mutation showed interallelic complementation with the R93H mutation (609058.0004). The patient was also homozygous also 2 other mutations which were presumably neutral: his532-to-arg (H532R) and val671-to-ile (V671I). Crane et al. (1992) compared the phenotype in the original patient and in 2 others with the G717V mutation. All 3 presented in the first years of life with multiple episodes of life-threatening organic acidosis and hyperammonemia. None had evidence of disease in the perinatal period, and all 3 were of low-normal intelligence. The authors concluded that the phenotype was intermediate between the fulminant and benign forms of methylmalonic aciduria, and suggested that the level of residual MUT enzyme activity associated with the G717V mutation may be close to the threshold required in vivo for maintaining metabolic homeostasis. </p><p>In a mutation screen of 160 patients with mut MMA, Worgan et al. (2006) found the G717V mutation in 12 of 29 black patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 METHYLMALONIC ACIDURIA, mut(-) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, GLU117TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918253,
|
|
|
|
|
|
|
|
ClinVar: RCV000001959, RCV000670836, RCV001384465, RCV001826404
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ogasawara et al. (1994) identified 2 novel mutations in the MUT gene, 1 of which was prevalent among Japanese patients with mut(-) MMA (251000). One patient was homozygous for a 425G-T transversion resulting in a glu117-to-ter (E117X) substitution. The E117X mutation was accompanied by instability of MCM mRNA, the first report of such a mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 METHYLMALONIC ACIDURIA, mut(-) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, 2-BP DEL, 769CA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2127419920,
|
|
|
|
|
|
|
|
ClinVar: RCV000001960
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with MMA mut(-) (251000), Ogasawara et al. (1994) found compound heterozygosity for 2 mutations in the MUT gene: the E117X mutation (609058.0006) frequent in Japanese patients and a 2-bp deletion (769delCA), resulting in a frameshift and premature termination. The termination occurred 508 amino acids upstream of the C-terminus of the protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, GLY623ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918254,
|
|
|
|
|
|
gnomAD: rs121918254,
|
|
|
|
|
|
ClinVar: RCV000001961, RCV000203390, RCV000427444, RCV001276633, RCV002271364, RCV004752676
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an African American male infant with MMA mut(0) (251000), Qureshi et al. (1994) identified compound heterozygosity for 2 mutations in the MUT gene: gly623-to-arg (G623R) and gly703-to-arg (G703R; 609058.0009). Cotransfection of each mutation with the R93H mutation mutation (609058.0004) stimulated propionate uptake, indicating that both mutations were independently capable of complementing the R93H mutation, whereas the G717V mutation (609058.0005) did not complement the G623R cell line. Qureshi et al. (1994) found that the MUT mutations identified in cell lines that exhibit intragenic complementation to G623R do not exhibit any specific pattern of charge or amino acid structure. Furthermore, neither the mut(0) versus mut(-) phenotype nor intragenic complementation could be predicted by the relative primary amino acid position. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, GLY703ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918255,
|
|
|
|
|
|
gnomAD: rs121918255,
|
|
|
|
|
|
ClinVar: RCV000001962, RCV005089146
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gly703-to-arg (G703R) mutation in the MUT gene that was found in compound heterozygous state in a patient with mut(0) methylmalonic aciduria (251000) by Qureshi et al. (1994), see 609058.0008. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, ASN219TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918256,
|
|
|
|
|
|
gnomAD: rs121918256,
|
|
|
|
|
|
ClinVar: RCV000001963, RCV000186055, RCV000203309, RCV000587363, RCV001271716
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 unrelated patients with MMA mut(0) (251000), Acquaviva et al. (2001) identified a 731A-T transversion in the MUT gene, resulting in an asn219-to-tyr (N219Y)in a conserved codon from bacteria to mouse and man. Mapping of the mutation onto a 3-dimensional model of human MCM suggested impaired folding and/or poor stability compatible with the mut(0) phenotype. Functional expression studies showed loss of enzyme activity. Three of the patients were homozygous for the N219Y mutation and 2 patients were compound heterozygous. The 5 patients were of French or Turkish descent, from a population of 19 patients with MCM apoenzyme deficiency, and the N219Y mutation represented 21% of the MUT alleles screened. Further screening for this mutation in 205 French children revealed 2 carriers, suggesting that N219Y is a frequent mutation in the French population and that the incidence of MMA might be underestimated. </p><p>The high frequency of N219Y in Caucasians was confirmed by the study of Acquaviva et al. (2005), who found that this allele represented 19% of the alleles tested among 40 European patients. Berger et al. (2001) detected the N219Y mutation in homozygous state in 2 of 7 Arab Muslim patients, suggesting that this mutation may also be frequent in this ethnic group. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, ARG108CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918257,
|
|
|
|
|
|
gnomAD: rs121918257,
|
|
|
|
|
|
ClinVar: RCV000001964, RCV000197802, RCV000203340, RCV001192656, RCV001271723, RCV001376644, RCV004018538, RCV004752677
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a screen of the MUT gene in 160 patients with mut MMA (251000), Worgan et al. (2006) found a novel mutation in exon 2, 322C-T (arg108 to cys, R108C), in 16 of 27 Hispanic patients. SNP phenotyping data demonstrated that Hispanic patients with this mutation shared a common haplotype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, GLY215SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918258,
|
|
|
|
|
|
|
|
ClinVar: RCV000001965, RCV000203381, RCV001851570
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Cavicchi et al. (2006) performed genetic and biochemical prenatal diagnosis at 11 weeks' gestation in a family with a proband affected by MMA (251000) due to homozygosity for a 643G-A transition in the MUT gene resulting in a gly215-to-ser substitution (G215S). Both chorionic villus and amniotic fluid samples were used. The presence of high levels of methylmalonic acid and propionylcarnitine determined by gas chromatography/mass spectrometry and tandem mass spectrometry analysis, respectively, and the identification of the G215S mutation in homozygosity in fetal DNA allowed a certain, rapid, and early diagnosis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, IVS11, C-A, -891
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1581819081,
|
|
|
|
|
|
|
|
ClinVar: RCV000001966
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Rincon et al. (2007) studied a patient with mut MMA (251000) who had been found by Martinez et al. (2005) to have a 76-bp insertion between exons 11 and 12 corresponding to an exon-like region in intron 11 (1957ins76). Rincon et al. (2007) found that the patient's DNA contained a C-to-A change in intron 11 at position +7 relative to the inserted sequence (IVS11-891C-A). Experimental confirmation that the change was pathogenic and caused the activation of the pseudoexon was obtained by use of a minigene. Rincon et al. (2007) used antisense morpholino oligonucleotides (AMOs) to target a cryptic splice site to block access of the splicing machinery in the pseudoexonic region in the pre-mRNA. Using this antisense therapeutics, they obtained correctly spliced mRNA that was effectively translated, and methylmalonyl CoA mutase (MCM) activity was rescued in the patients' fibroblasts. The effect of the AMO was sequence- and dose-dependent. Close to 100% of MCM activity, measured by incorporation of (14)C-propionate, was obtained after 48 hours, and correctly spliced MUT mRNA was still detected 15 days after treatment. The patient with MUT deficiency studied by Rincon et al. (2007) was compound heterozygous for the intronic insertion and a splicing mutation in the last nucleotide of exon 10 (1808G-A; 609058.0014), and had 2 aberrant transcripts as a result of the use of cryptic splice sites. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 METHYLMALONIC ACIDURIA, mut(0) TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MMUT, 1808G-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1412463565,
|
|
|
|
|
|
gnomAD: rs1412463565,
|
|
|
|
|
|
ClinVar: RCV000001967, RCV003555894
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the splice site mutation in the MUT gene (1808G-A) that was found in compound heterozygous state in a patient with mut MMA (251000) by Rincon et al. (2007), see 609058.0013. </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">
|
|
Ledley (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">
|
|
Acquaviva, C., Benoist, J.-F., Callebaut, I., Guffon, N., Ogier de Baulny, H., Touati, G., Aydin, A., Porquet, D., Elion, J.
|
|
<strong>N219Y, a new frequent mutation among mut-0 forms of methylmalonic acidemia in Caucasian patients.</strong>
|
|
Europ. J. Hum. Genet. 9: 577-582, 2001.
|
|
|
|
|
|
[PubMed: 11528502]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200675]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Acquaviva, C., Benoist, J.-F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D., Elion, J.
|
|
<strong>Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(0) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.</strong>
|
|
Hum. Mutat. 25: 167-176, 2005.
|
|
|
|
|
|
[PubMed: 15643616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20128]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Adjalla, C. E., Hosack, A. R., Gilfix, B. M., Lamothe, E., Sun, S., Chan, A., Evans, S., Matiaszuk, N. V., Rosenblatt, D. S.
|
|
<strong>Seven novel mutations in mut methylmalonic aciduria.</strong>
|
|
Hum. Mutat. 11: 270-274, 1998.
|
|
|
|
|
|
[PubMed: 9554742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<270::AID-HUMU3>3.0.CO;2-T]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berger, I., Shaag, A., Anikster, Y., Baumgartner, E. R., Bar-Meir, M., Joseph, A., Elpeleg, O. N.
|
|
<strong>Mutation analysis of the MCM gene in Israeli patients with mut(0) disease.</strong>
|
|
Molec. Genet. Metab. 73: 107-110, 2001.
|
|
|
|
|
|
[PubMed: 11350191]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/mgme.2001.3166]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blanche, H., Zoghbi, H. Y., Jabs, E. W., de Gouyon, B., Zunec, R., Dausset, J., Cann, H. M.
|
|
<strong>A centromere-based genetic map of the short arm of human chromosome 6.</strong>
|
|
Genomics 9: 420-428, 1991.
|
|
|
|
|
|
[PubMed: 2032717]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90407-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cavicchi, C., Donati, M. A., Funghini, S., la Marca, G., Malvagia, S., Ciani, F., Poggi, G. M., Pasquini, E., Zammarchi, E., Morrone, A.
|
|
<strong>Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria.</strong>
|
|
Clin. Genet. 69: 72-76, 2006.
|
|
|
|
|
|
[PubMed: 16451139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00547.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Champattanachai, V., Ketudat Cairns, J. R., Shotelersuk, V., Keeratichamroen, S., Sawangareetrakul, P., Srisomsap, C., Kaewpaluek, V., Svasti, J.
|
|
<strong>Novel mutations in a Thai patient with methylmalonic acidemia.</strong>
|
|
Molec. Genet. Metab. 79: 300-302, 2003.
|
|
|
|
|
|
[PubMed: 12948746]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1096-7192(03)00106-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crane, A. M., Jansen, R., Andrews, E. R., Ledley, F. D.
|
|
<strong>Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut(-) methylmalonic aciduria.</strong>
|
|
J. Clin. Invest. 89: 385-391, 1992.
|
|
|
|
|
|
[PubMed: 1346616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115597]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crane, A. M., Ledley, F. D.
|
|
<strong>Clustering of mutations in methylmalonyl CoA mutase associated with mut(-) methylmalonic acidemia.</strong>
|
|
Am. J. Hum. Genet. 55: 42-50, 1994.
|
|
|
|
|
|
[PubMed: 7912889]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crane, A. M., Martin, L. S., Valle, D., Ledley, F. D.
|
|
<strong>Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase.</strong>
|
|
Hum. Genet. 89: 259-264, 1992.
|
|
|
|
|
|
[PubMed: 1351030]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220536]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Drennan, C. L., Matthews, R. G., Rosenblatt, D. S., Ledley, F. D., Fenton, W. A., Ludwig, M. L.
|
|
<strong>Molecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: deductions from the structure of methionine synthase.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 5550-5555, 1996.
|
|
|
|
|
|
[PubMed: 8643613]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.11.5550]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fenton, W. A., Hack, A. M., Kraus, J. P., Rosenberg, L. E.
|
|
<strong>Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 1421-1424, 1987.
|
|
|
|
|
|
[PubMed: 2881300]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.84.5.1421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Forny, P., Froese, D. S., Suormala, T., Yue, W. W., Baumgartner, M. R.
|
|
<strong>Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.</strong>
|
|
Hum. Mutat. 35: 1449-1458, 2014.
|
|
|
|
|
|
[PubMed: 25125334]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22633]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janata, J., Kogekar, N., Fenton, W. A.
|
|
<strong>Expression and kinetic characterization of methylmalonyl-CoA mutase from patients with the mut- phenotype: evidence for naturally occurring interallelic complementation.</strong>
|
|
Hum. Molec. Genet. 6: 1457-1464, 1997.
|
|
|
|
|
|
[PubMed: 9285782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.9.1457]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jansen, R., Kalousek, F., Fenton, W. A., Rosenberg, L. E., Ledley, F. D.
|
|
<strong>Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction.</strong>
|
|
Genomics 4: 198-205, 1989.
|
|
|
|
|
|
[PubMed: 2567699]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(89)90300-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jansen, R., Ledley, F. D.
|
|
<strong>Heterozygous mutations at the mut locus in fibroblasts with mut-0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning.</strong>
|
|
Am. J. Hum. Genet. 47: 808-814, 1990.
|
|
|
|
|
|
[PubMed: 1977311]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Crane, A. M., Lumetta, M.
|
|
<strong>Heterogeneous alleles and expression of methylmalonyl CoA mutase in mut methylmalonic acidemia.</strong>
|
|
Am. J. Hum. Genet. 46: 539-547, 1990.
|
|
|
|
|
|
[PubMed: 1968706]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Jansen, R., Nham, S.-U., Fenton, W. A., Rosenberg, L. E.
|
|
<strong>Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes mut-0 methylmalonic acidemia.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 3147-3150, 1990.
|
|
|
|
|
|
[PubMed: 1970180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.8.3147]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Lumetta, M., Nguyen, P. N., Kolhouse, J. F., Allen, R. H.
|
|
<strong>Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut cell lines.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 3518-3521, 1988.
|
|
|
|
|
|
[PubMed: 2453061]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.85.10.3518]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Lumetta, M. R., Zoghbi, H. Y., vanTuinen, P., Ledbetter, S. A., Ledbetter, D. H.
|
|
<strong>Mapping of human methylmalonyl CoA mutase (MUT) locus on chromosome 6.</strong>
|
|
Am. J. Hum. Genet. 42: 839-846, 1988.
|
|
|
|
|
|
[PubMed: 2897160]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., Rosenblatt, D. S.
|
|
<strong>Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations.</strong>
|
|
Hum. Mutat. 9: 1-6, 1997.
|
|
|
|
|
|
[PubMed: 8990001]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)9:1<1::AID-HUMU1>3.0.CO;2-E]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D., vanTuinen, P., Ledbetter, S. A., Ledbetter, D.
|
|
<strong>Assignment of methylmalonyl CoA mutase locus to human chromosome 6. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 646 only, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ledley, F. D.
|
|
<strong>Perspectives on methylmalonic acidemia resulting from molecular cloning of methylmalonyl CoA mutase.</strong>
|
|
BioEssays 12: 335-340, 1990.
|
|
|
|
|
|
[PubMed: 1975493]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/bies.950120706]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martinez, M. A., Rincon, A., Desviat, L. R., Merinero, B., Ugarte, M., Perez, B.
|
|
<strong>Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.</strong>
|
|
Molec. Genet. Metab. 84: 317-325, 2005.
|
|
|
|
|
|
[PubMed: 15781192]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2004.11.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nham, S.-U., Wilkemeyer, M. F., Ledley, F. D.
|
|
<strong>Structure of the human methylmalonyl-CoA mutase (MUT) locus.</strong>
|
|
Genomics 8: 710-716, 1990.
|
|
|
|
|
|
[PubMed: 1980486]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90259-w]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ogasawara, M., Matsubara, Y., Mikami, H., Narisawa, K.
|
|
<strong>Identification of two novel mutations in the methylmalonyl-CoA mutase gene with decreased levels of mutant mRNA in methylmalonic acidemia.</strong>
|
|
Hum. Molec. Genet. 3: 867-872, 1994.
|
|
|
|
|
|
[PubMed: 7951229]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.6.867]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Qureshi, A. A., Crane, A. M., Matiaszuk, N. V., Rezvani, I., Ledley, F. D., Rosenblatt, D. S.
|
|
<strong>Cloning and expression of mutations demonstrating intragenic complementation in mut-0 methylmalonic aciduria.</strong>
|
|
J. Clin. Invest. 93: 1812-1819, 1994.
|
|
|
|
|
|
[PubMed: 7909321]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI117166]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raff, M. L., Crane, A. M., Jansen, R., Ledley, F. D., Rosenblatt, D. S.
|
|
<strong>Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut(0) and mut(-) methylmalonic aciduria by interallelic complementation.</strong>
|
|
J. Clin. Invest. 87: 203-207, 1991.
|
|
|
|
|
|
[PubMed: 1670635]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI114972]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Remacle, N., Forny, P., Cudre-Cung, H.-P., Gonzalez-Melo, M., do Vale-Pereira, S., Henry, H., Teav, T., Gallart-Ayala, H., Braissant, O., Baumgartner, M., Ballhausen, D.
|
|
<strong>New in vitro model derived from brain-specific Mut-/- mice confirms cerebral ammonium accumulation in methylmalonic aciduria.</strong>
|
|
Molec. Genet. Metab. 124: 266-277, 2018.
|
|
|
|
|
|
[PubMed: 29934063]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2018.06.008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B.
|
|
<strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong>
|
|
Am. J. Hum. Genet. 81: 1262-1270, 2007.
|
|
|
|
|
|
[PubMed: 17966092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/522376]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sertic, J., Vincek, V., Ledley, F. D., Figueroa, F., Klein, J.
|
|
<strong>Mapping of the L-methylmalonyl-CoA mutase gene to mouse chromosome 17.</strong>
|
|
Genomics 6: 560-564, 1990.
|
|
|
|
|
|
[PubMed: 1970332]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90487-f]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takeshima, Y., Yagi, M., Wada, H., Ishibashi, K., Nishiyama, A., Kakumoto, M., Sakaeda, T., Saura, R., Okumura, K., Matsuo, M.
|
|
<strong>Intravenous infusion of an antisense oligonucleotide results in exon skipping in muscle dystrophin mRNA of Duchenne muscular dystrophy.</strong>
|
|
Pediat. Res. 59: 690-694, 2006.
|
|
|
|
|
|
[PubMed: 16627883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/01.pdr.0000215047.51278.7c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Threadgill, D. W., Wilkemeyer, M., Womack, J. E., Ledley, F. D.
|
|
<strong>Localization of the murine methylmalonyl CoA mutase (Mut) locus on chromosome 17 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 53: 112-114, 1990.
|
|
|
|
|
|
[PubMed: 1973376]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000132907]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Worgan, L. C., Niles, K., Tirone, J. C., Hofmann, A., Verner, A., Sammak, A., Kucic, T., Lepage, P., Rosenblatt, D. S.
|
|
<strong>Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.</strong>
|
|
Hum. Mutat. 27: 31-43, 2006.
|
|
|
|
|
|
[PubMed: 16281286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20258]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zoghbi, H. Y., O'Brien, W. E., Ledley, F. D.
|
|
<strong>Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6.</strong>
|
|
Genomics 3: 396-398, 1988.
|
|
|
|
|
|
[PubMed: 2907507]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(88)90135-8]
|
|
|
|
|
|
</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">
|
|
Hilary J. Vernon - updated : 01/14/2022<br>Ada Hamosh - updated : 12/07/2018<br>Victor A. McKusick - updated : 11/28/2007<br>Victor A. McKusick - updated : 3/7/2006<br>Victor A. McKusick - updated : 1/20/2006<br>Victor A. McKusick - updated : 3/7/2005<br>Cassandra L. Kniffin - updated : 12/6/2004
|
|
</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">
|
|
Cassandra L. Kniffin : 12/1/2004
|
|
</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 : 01/08/2024<br>carol : 06/14/2022<br>carol : 01/14/2022<br>carol : 12/20/2021<br>carol : 02/26/2020<br>alopez : 12/07/2018<br>alopez : 07/22/2015<br>mcolton : 6/26/2015<br>carol : 3/28/2013<br>terry : 5/31/2011<br>wwang : 5/12/2011<br>alopez : 12/11/2007<br>alopez : 12/11/2007<br>alopez : 12/11/2007<br>terry : 11/28/2007<br>terry : 11/16/2006<br>alopez : 3/14/2006<br>alopez : 3/14/2006<br>terry : 3/7/2006<br>alopez : 2/15/2006<br>terry : 1/20/2006<br>terry : 4/21/2005<br>carol : 4/5/2005<br>tkritzer : 3/14/2005<br>terry : 3/7/2005<br>carol : 12/10/2004<br>ckniffin : 12/6/2004
|
|
</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>
|
|
|
|
|