7158 lines
664 KiB
Text
7158 lines
664 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
|
|
|
|
- *600509 - ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 8; ABCC8
|
|
|
|
|
|
- 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=600509"><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 class="hidden-sm hidden-xs">
|
|
|
|
|
|
Display:
|
|
|
|
|
|
<label style="font-weight: normal"><input type="checkbox" id="mimToggleChangeBars" checked /> Change Bars </label>
|
|
|
|
|
|
</span>
|
|
|
|
|
|
</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">*600509</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="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</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/600509">Table View</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=ENSG00000006071;t=ENST00000389817" 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=6833" 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=600509" 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=ENSG00000006071;t=ENST00000389817" 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_000352,NM_001287174,NM_001351295,NM_001351296,NM_001351297,NR_147094" 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_000352" 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=600509" 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=02741&isoform_id=02741_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/ABCC8" 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/784882,1369844,1374919,1374920,1480871,1480907,3643190,62087748,118582255,119588842,119588843,221041878,305855251,311033501,562815400,1189438336,1189438338,1189438340,1214987473,1214987795,1219731505" 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/Q09428" 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=6833" 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=ENSG00000006071;t=ENST00000389817" 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=ABCC8" 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=ABCC8" 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+6833" 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/ABCC8" 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:6833" 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/6833" 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=chr11&hgg_gene=ENST00000389817.8&hgg_start=17392498&hgg_end=17476845&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:59" 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:59" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600509[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=600509[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/ABCC8/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000006071" 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=ABCC8" 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=ABCC8" 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=ABCC8" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ABCC8&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/PA24395" 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:59" 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://flybase.org/reports/FBgn0028675.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:1352629" 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/ABCC8#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:1352629" 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/6833/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=6833" 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://zfin.org/ZDB-GENE-050517-22" 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:6833" 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=ABCC8&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 44054006, 609580007, 62151007<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> E11<br />
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
600509
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 8; ABCC8
|
|
|
|
</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">
|
|
SULFONYLUREA RECEPTOR; SUR<br />
|
|
SUR1<br />
|
|
SULFONYLUREA RECEPTOR, BETA CELL HIGH AFFINITY
|
|
</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=ABCC8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ABCC8</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/11/209?start=-3&limit=10&highlight=209">11p15.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:17392498-17476845&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'})">11:17,392,498-17,476,845</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
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=125853,618857,610374,256450,240800" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="5">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/209?start=-3&limit=10&highlight=209">
|
|
11p15.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, noninsulin-dependent
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/125853"> 125853 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, permanent neonatal 3, with or without neurologic features
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618857"> 618857 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, transient neonatal 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/610374"> 610374 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hyperinsulinemic hypoglycemia, familial, 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/256450"> 256450 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypoglycemia of infancy, leucine-sensitive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/240800"> 240800 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</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/600509" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/600509" 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="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">
|
|
<div class="mim-changed mim-change"><p>Sulfonylureas are a class of drugs widely used as oral hypoglycemics to promote insulin secretion in the treatment of type 2 diabetes mellitus (T2D, NIDDM; see <a href="/entry/125853">125853</a>). These drugs interact with the sulfonylurea receptor of pancreatic beta cells and inhibit the conductance of adenosine triphosphate (ATP)-dependent potassium channels. <a href="#1" class="mim-tip-reference" title="Aguilar-Bryan, L., Nichols, C. G., Wechsler, S. W., Clement, J. P., IV, Boyd, A. E., III, Gonzalez, G., Herrera-Sosa, H., Nguy, K., Bryan, J., Nelson, D. A. <strong>Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.</strong> Science 268: 423-426, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716547</a>] [<a href="https://doi.org/10.1126/science.7716547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716547">Aguilar-Bryan et al. (1995)</a> cloned the cDNA for the high-affinity sulfonylurea receptor. Analysis of the predicted amino acid sequence indicated that the gene is a member of the ATP-binding cassette or traffic ATPase superfamily with multiple membrane-spanning domains and 2 nucleotide-binding folds. The results suggested that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect K(ATP) channel activity, and thereby modulate insulin release. Biochemical studies by <a href="#1" class="mim-tip-reference" title="Aguilar-Bryan, L., Nichols, C. G., Wechsler, S. W., Clement, J. P., IV, Boyd, A. E., III, Gonzalez, G., Herrera-Sosa, H., Nguy, K., Bryan, J., Nelson, D. A. <strong>Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.</strong> Science 268: 423-426, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716547</a>] [<a href="https://doi.org/10.1126/science.7716547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716547">Aguilar-Bryan et al. (1995)</a> indicated that SUR is a large membrane protein (140 to 170 kD). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716547" 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></div>
|
|
</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>By fluorescence in situ hybridization, <a href="#39" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J. <strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Science 268: 426-429, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>] [<a href="https://doi.org/10.1126/science.7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716548">Thomas et al. (1995)</a> showed that the SUR gene maps to 11p15.1. <a href="#21" class="mim-tip-reference" title="Inagaki, N., Gonoi, T., Clement, J. P., IV., Namba, N., Inazawa, J., Gonzalez, G., Aguilar-Bryan, L., Seino, S., Bryan, J. <strong>Reconstitution of I(KATP): an inward rectifier subunit plus the sulfonylurea receptor.</strong> Science 270: 1166-1169, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7502040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7502040</a>] [<a href="https://doi.org/10.1126/science.270.5239.1166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7502040">Inagaki et al. (1995)</a> determined that the BIR (<a href="/entry/600937">600937</a>) and SUR genes are clustered at 11p15.1, with the BIR gene immediately 3-prime of the SUR gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7502040+7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#21" class="mim-tip-reference" title="Inagaki, N., Gonoi, T., Clement, J. P., IV., Namba, N., Inazawa, J., Gonzalez, G., Aguilar-Bryan, L., Seino, S., Bryan, J. <strong>Reconstitution of I(KATP): an inward rectifier subunit plus the sulfonylurea receptor.</strong> Science 270: 1166-1169, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7502040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7502040</a>] [<a href="https://doi.org/10.1126/science.270.5239.1166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7502040">Inagaki et al. (1995)</a> coexpressed SUR with BIR and observed reconstitution of an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to ATP, inhibited by sulfonylureas, and activated by diazoxide. The authors concluded that these pancreatic beta-cell potassium channels are a complex composed of at least 2 subunits: BIR and SUR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7502040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Philipson, L. H., Steiner, D. F. <strong>Pas de deux or more: the sulfonylurea receptor and K+ channels.</strong> Science 268: 372-373, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716539</a>] [<a href="https://doi.org/10.1126/science.7716539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716539">Philipson and Steiner (1995)</a> discussed the significance of the work on SUR. They compared the SUR protein with other members of the family of ATP-binding cassette proteins, including the multidrug resistance (MDR) proteins (e.g., <a href="/entry/171050">171050</a>), which cause chemotherapeutic drug resistance when overexpressed, and the CFTR protein (<a href="/entry/602421">602421</a>), which is mutant in patients with cystic fibrosis (<a href="/entry/219700">219700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716539" 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 test the effect of abolition of ATP hydrolysis on K-ATP channel activation by Mg-ADP and diazoxide in Xenopus oocytes, <a href="#17" class="mim-tip-reference" title="Gribble, F. M., Tucker, S. J., Ashcroft, F. M. <strong>The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.</strong> EMBO J. 16: 1145-1152, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9135131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9135131</a>] [<a href="https://doi.org/10.1093/emboj/16.6.1145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9135131">Gribble et al. (1997)</a> mutated the critical lysine residues of the Walker A motifs in the first (K719A) and second (K1384M) nucleotide-binding domains (NBDs) of SUR1. The Walker A lysine of NBD1, but not of NBD2, was essential for activation. Both Walker A lysines were essential for potentiation by Mg-ADP. Mutant currents were more sensitive to inhibition by ATP than were wildtype currents. Metabolic inhibition led to activation of wildtype and K1384M currents, but not K719A or K719A/K1384M currents. These results suggested to the authors that an additional factor, besides ATP and ADP, regulates K-ATP channel activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9135131" 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="#33" class="mim-tip-reference" title="Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., Rossetti, L. <strong>Hypothalamic K(ATP) channels control hepatic glucose production.</strong> Nature 434: 1026-1031, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846348</a>] [<a href="https://doi.org/10.1038/nature03439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846348">Pocai et al. (2005)</a> demonstrated that activation of K-ATP channels in the mediobasal hypothalamus is sufficient to lower blood glucose levels through inhibition of hepatic gluconeogenesis. The infusion of a K-ATP blocker within the mediobasal hypothalamus, or the surgical resection of the hepatic branch of the vagus nerve, negated the effects of central insulin (<a href="/entry/176730">176730</a>) and halved the effects of systemic insulin on hepatic glucose production in the mouse. Consistent with these results, mice lacking the SUR1 subunit of the K-ATP channel were resistant to the inhibitory action of insulin on gluconeogenesis. <a href="#33" class="mim-tip-reference" title="Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., Rossetti, L. <strong>Hypothalamic K(ATP) channels control hepatic glucose production.</strong> Nature 434: 1026-1031, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846348</a>] [<a href="https://doi.org/10.1038/nature03439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846348">Pocai et al. (2005)</a> concluded that activation of hypothalamic K-ATP channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15846348" 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><strong><em>Familial Hyperinsulinemic Hypoglycemia 1</em></strong>
|
|
</p>
|
|
|
|
<p>Familial hyperinsulinemic hypoglycemia (see HHF1, <a href="/entry/256450">256450</a>), a disorder characterized by unregulated insulin secretion, was mapped to 11p15.1-p14 by linkage analysis (<a href="#13" class="mim-tip-reference" title="Glaser, B., Chiu, K. C., Anker, R., Nestorowicz, A., Landau, H., Ben-Bassat, H., Shlomai, Z., Kaiser, N., Thornton, P. S., Stanley, C. A., Spielman, R. S., Gogolin-Ewens, K., Cerasi, E., Baker, L., Rice, J., Donis-Keller, H., Permutt, M. A. <strong>Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene.</strong> Nature Genet. 7: 185-188, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7920639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7920639</a>] [<a href="https://doi.org/10.1038/ng0694-185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7920639">Glaser et al., 1994</a>; <a href="#38" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Hallman, D. M., Mathew, P. M. <strong>Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Am. J. Hum. Genet. 56: 416-421, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847376</a>]" pmid="7847376">Thomas et al., 1995</a>; <a href="#9" class="mim-tip-reference" title="Fantes, J. A., Oghene, K., Boyle, S., Danes, S., Fletcher, J. M., Bruford, E. A., Williamson, K., Seawright, A., Schedl, A., Hanson, I., Zehetner, G., Bhogal, R., Lehrach, H., Gregory, S., Williams, J., Little, P. F. R., Sellar, G. C., Hoovers, J., Mannens, M., Weissenbach, J., Junien, C., van Heyningen, V., Bickmore, W. A. <strong>A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.</strong> Genomics 25: 447-461, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789978</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80045-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789978">Fantes et al., 1995</a>). The SUR protein was thought to be a likely candidate since it is a putative subunit of the beta-cell ATP-sensitive potassium channel, K(ATP), a modulator of insulin secretion. <a href="#39" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J. <strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Science 268: 426-429, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>] [<a href="https://doi.org/10.1126/science.7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716548">Thomas et al. (1995)</a> detected 2 separate SUR gene splice site mutations that segregated with the disease phenotype in affected individuals from 9 different families (<a href="#0001">600509.0001</a> and <a href="#0002">600509.0002</a>). Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide-binding domain (NBF2) of the SUR protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7920639+7847376+7716548+7789978" 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 further studies on the role of the SUR nucleotide-binding folds in hyperinsulinemic hypoglycemia, <a href="#40" class="mim-tip-reference" title="Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J. <strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Am. J. Hum. Genet. 59: 510-518, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751851</a>]" pmid="8751851">Thomas et al. (1996)</a> demonstrated that disruption of the first nucleotide-binding fold (NBF1) likewise leads to HHF (<a href="#0003">600509.0003</a>-<a href="#0005">600509.0005</a>). The data indicated that both nucleotide-binding-fold regions of the sulfonylurea receptor are required for normal regulation of beta-cell ATP-dependent potassium channel activity and insulin secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8751851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#29" class="mim-tip-reference" title="Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A. <strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong> Hum. Molec. Genet. 5: 1813-1822, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923011">Nestorowicz et al. (1996)</a> screened a proband from each of 25 Ashkenazi Jewish families with hyperinsulinemic hypoglycemia for mutations in the SUR gene by SSCP analysis of genomic DNA and subsequent sequence analysis. They identified 2 common mutations. One mutation was a novel in-frame deletion of the codon for F1388 (<a href="#0006">600509.0006</a>). This mutation creates a unique BseR1 restriction site in exon 34 allowing detection of noncarriers, homozygotes, and heterozygotes. The second mutation was a previously described G-to-A transition at position -9 of the 3-prime splice site of intron 32 (<a href="#0002">600509.0002</a>). Extended haplotype analysis in the D11S1901-D11S1310 region revealed that these 2 mutations were associated with an H1 haplotype in 88% of patients studied, suggesting a founder effect. <a href="#29" class="mim-tip-reference" title="Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A. <strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong> Hum. Molec. Genet. 5: 1813-1822, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923011">Nestorowicz et al. (1996)</a> determined that F1388-deleted SUR is unable to form a functional K(ATP) channel with Kir6.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#28" class="mim-tip-reference" title="Nestorowicz, A., Glaser, B., Wilson, B. A., Shyng, S.-L., Nichols, C. G., Stanley, C. A., Thornton, P. S., Permutt, M. A. <strong>Genetic heterogeneity in familial hyperinsulinism.</strong> Hum. Molec. Genet. 7: 1119-1128, 1998. Note: Erratum: Hum. Molec. Genet. 7: 1527 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618169</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618169">Nestorowicz et al. (1998)</a> screened 45 familial hyperinsulinism probands of various ethnic origins for mutations in the SUR gene. SSCP and nucleotide sequence analyses of genomic DNA revealed a total of 17 novel and 3 previously described mutations. The novel mutations comprised 1 nonsense and 10 missense mutations, 2 deletions, 3 mutations in consensus splice site sequences, and an in-frame insertion of 6 nucleotides. One mutation occurred in the first nucleotide-binding domain (NBF1) of the SUR molecule and another 8 mutations were located in the second nucleotide-binding domain (NBF2), including 2 at highly conserved amino acid residues within the Walker A sequence motif. Most of the other mutations were distributed throughout the 3 putative transmembrane domains of the SUR protein. With the exception of the 3993-9G-A mutation (<a href="#0002">600509.0002</a>), which was detected on 4.5% (4 of 88) disease chromosomes, allelic frequencies for the identified mutations varied between 1.1% and 2.3%. The clinical manifestations of familial hyperinsulinism in those patients homozygous for mutations in the SUR gene were described. In contrast to the allelic homogeneity of familial hyperinsulinism found in Ashkenazi Jewish patients (<a href="#29" class="mim-tip-reference" title="Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A. <strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong> Hum. Molec. Genet. 5: 1813-1822, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923011">Nestorowicz et al., 1996</a>), the findings of the wider study suggested that a large degree of allelic heterogeneity at the SUR locus exists in non-Ashkenazi patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8923011+9618169" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p>From a morphologic standpoint, there are 2 types of histopathologic lesions underlying PHHI: a focal adenomatous hyperplasia of islet cells of the pancreas in approximately 30% of sporadic cases, and a diffuse form. In sporadic focal forms, specific losses of maternal alleles (LOH) of the imprinted chromosomal region 11p15, restricted to the hyperplastic area of the pancreas, were detected by <a href="#5" class="mim-tip-reference" title="de Lonlay, P., Fournet, J.-C., Rahier, J., Gross-Morand, M.-S., Poggi-Travert, F., Foussier, V., Bonnefont, J.-P., Brusset, M.-C., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C. <strong>Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.</strong> J. Clin. Invest. 100: 802-807, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259578</a>] [<a href="https://doi.org/10.1172/JCI119594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259578">de Lonlay et al. (1997)</a>. Similar mechanisms are observed in embryonal tumors and in the Beckwith-Wiedemann syndrome (BWS; <a href="/entry/130650">130650</a>); the latter condition is also associated with neonatal but transient hyperinsulinism. The same chromosomal region, 11p15.1, includes the SUR gene and the KCNJ11 gene (<a href="/entry/600937">600937</a>), which code for the 2 subunits of the beta-cell K(+)-ATP channel. Recessive mutations in these genes cause recessive familial forms of PHHI, but appear not to be imprinted. Although the parental bias in loss of maternal alleles did not argue in favor of direct involvement of the SUR or KCNJ11 genes, the LOH may unmask a recessive mutation leading to persistent hyperinsulinism. <a href="#44" class="mim-tip-reference" title="Verkarre, V., Fournet, J.-C., de Lonlay, P., Gross-Morand, M.-S., Devillers, M., Rahier, J., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C. <strong>Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.</strong> J. Clin. Invest. 102: 1286-1291, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9769320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9769320</a>] [<a href="https://doi.org/10.1172/JCI4495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9769320">Verkarre et al. (1998)</a> reported somatic reduction to hemizygosity or homozygosity of a paternal SUR constitutional heterozygous mutation in 4 patients with a focal form of PHHI. Thus, this somatic event, which leads to both beta cell proliferation and hyperinsulinism, can be considered as the somatic equivalent, restricted to a microscopic focal lesion, of constitutional uniparental disomy associated with unmasking of a heterozygous paternal mutation leading to a somatic recessive disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9259578+9769320" 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="#36" class="mim-tip-reference" title="Ryan, F., Devaney, D., Joyce, C., Nestorowicz, A., Permutt, M. A., Glaser, B., Barton, D. E., Thornton, P. S. <strong>Hyperinsulinism: molecular aetiology of focal disease.</strong> Arch. Dis. Child 79: 445-447, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10193261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10193261</a>] [<a href="https://doi.org/10.1136/adc.79.5.445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10193261">Ryan et al. (1998)</a> reported a similar situation in a non-Jewish hyperinsulinism patient with a single, paternally inherited SUR1 mutation. <a href="#14" class="mim-tip-reference" title="Glaser, B., Furth, J., Stanley, C. A., Baker, L., Thornton, P. S., Landau, H., Permutt, M. A. <strong>Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.</strong> Hum. Mutat. 14: 23-29, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447255</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<23::AID-HUMU3>3.0.CO;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447255">Glaser et al. (1999)</a> proposed that some or all of the subjects with paternally inherited SUR1 mutations may have focal disease. In the 2 patients who underwent surgery, focal adenomatosis was documented. In one of these patients, tissue was available and reduction to homozygosity for the SUR1 mutation was also documented. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10447255+10193261" 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="Glaser, B., Ryan, F., Donath, M., Landau, H., Stanley, C. A., Baker, L., Barton, D. E., Thornton, P. S. <strong>Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene.</strong> Diabetes 48: 1652-1657, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10426386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10426386</a>] [<a href="https://doi.org/10.2337/diabetes.48.8.1652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10426386">Glaser et al. (1999)</a> examined pancreatic tissue from 3 patients with single paternal-allele mutations of the SUR1 gene and found focal beta-cell hyperplasia. DNA extracted from the focal lesions and adjacent normal pancreas revealed loss of the maternal chromosome 11p15, resulting in reduction to homozygosity for the SUR1 mutation, within the focal lesions only. <a href="#15" class="mim-tip-reference" title="Glaser, B., Ryan, F., Donath, M., Landau, H., Stanley, C. A., Baker, L., Barton, D. E., Thornton, P. S. <strong>Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene.</strong> Diabetes 48: 1652-1657, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10426386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10426386</a>] [<a href="https://doi.org/10.2337/diabetes.48.8.1652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10426386">Glaser et al. (1999)</a> suggested that the combination of a paternally inherited SUR1 mutation along with somatic loss of the maternal allele of chromosome 11p may be the genetic etiology of most, if not all, cases of focal hyperinsulinism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10426386" 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>
|
|
|
|
<div class="mim-changed mim-change"><p>In 15 of 24 Finnish patients with hyperinsulinemic hypoglycemia, <a href="#30" class="mim-tip-reference" title="Otonkoski, T., Ammala, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K., Ashfield, R., Huang, E., Komulainen, J., Ashcroft, F. M., Dunne, M. J., Kere, J., Thomas, P. M. <strong>A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.</strong> Diabetes 48: 408-415, and 415, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10334322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10334322</a>] [<a href="https://doi.org/10.2337/diabetes.48.2.408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10334322">Otonkoski et al. (1999)</a> identified homozygosity or heterozygosity for a V187D mutation in the ABCC8 gene (<a href="#0013">600509.0013</a>). The mutation was not found in 23 patients with hyperinsulinemic hypoglycemia from outside Finland, suggestive of a founder effect. In vitro studies demonstrated that the presence of the V187D mutation renders the potassium channel completely nonfunctional. Parents and sibs who were carriers of the mutation were apparently asymptomatic; <a href="#30" class="mim-tip-reference" title="Otonkoski, T., Ammala, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K., Ashfield, R., Huang, E., Komulainen, J., Ashcroft, F. M., Dunne, M. J., Kere, J., Thomas, P. M. <strong>A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.</strong> Diabetes 48: 408-415, and 415, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10334322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10334322</a>] [<a href="https://doi.org/10.2337/diabetes.48.2.408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10334322">Otonkoski et al. (1999)</a> postulated the presence of another mutation in heterozygous affected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10334322" 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></div>
|
|
|
|
<p>In 5 affected members of the 3-generation family ('family 1') with hyperinsulinemic hypoglycemia originally reported by <a href="#42" class="mim-tip-reference" title="Thornton, P. S., Satin-Smith, M. S., Herold, K., Glaser, B., Chiu, K. C., Nestorowicz, A., Permutt, M. A., Baker, L., Stanley, C. A. <strong>Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.</strong> J. Pediat. 132: 9-14, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9469993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9469993</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70477-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9469993">Thornton et al. (1998)</a>, <a href="#41" class="mim-tip-reference" title="Thornton, P. S., MacMullen, C., Ganguly, A., Ruchelli, E., Steinkrauss, L., Crane, A., Aguilar-Bryan, L., Stanley, C. A. <strong>Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.</strong> Diabetes 52: 2403-2410, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12941782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12941782</a>] [<a href="https://doi.org/10.2337/diabetes.52.9.2403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12941782">Thornton et al. (2003)</a> identified heterozygosity for a 3-bp deletion in exon 34 of the ABCC8 gene (<a href="#0014">600509.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12941782+9469993" 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 an infant of Spanish descent with hyperinsulinemic hypoglycemia, <a href="#43" class="mim-tip-reference" title="Tornovsky, S., Crane, A., Cosgrove, K. E., Hussain, K., Lavie, J., Heyman, M., Nesher, Y., Kuchinski, N., Ben-Shushan, E., Shatz, O., Nahari, E., Potikha, T., and 11 others. <strong>Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.</strong> J. Clin. Endocr. Metab. 89: 6224-6234, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15579781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15579781</a>] [<a href="https://doi.org/10.1210/jc.2004-1233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15579781">Tornovsky et al. (2004)</a> identified a mutation in the promoter of the ABCC8 gene (<a href="#0015">600509.0015</a>) on the paternal allele. No mutation was found on the maternal allele. No focal lesion had been identified after near-total pancreatectomy, but the specimen was not available for reevaluation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15579781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#18" class="mim-tip-reference" title="Henwood, M. J., Kelly, A., MacMullen, C., Bhatia, P., Ganguly, A., Thornton, P. S., Stanley, C. A. <strong>Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.</strong> J. Clin. Endocr. Metab. 90: 789-794, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15562009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15562009</a>] [<a href="https://doi.org/10.1210/jc.2004-1604" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15562009">Henwood et al. (2005)</a> measured acute insulin responses (AIRs) to calcium, leucine, glucose, and tolbutamide in 22 infants with recessive ABCC8 or KCNJ11 mutations, 8 of whom had diffuse hyperinsulinism and 14 of whom had focal hyperinsulinism. Of the 24 total mutations, 7 showed evidence of residual K(ATP) channel function: 2 of the patients with partial defects were homozygous and 4 heterozygous for amino acid substitutions or insertions, and 1 was a compound heterozygote for 2 premature stop codons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15562009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#12" class="mim-tip-reference" title="Giurgea, I., Sempoux, C., Bellanne-Chantelot, C., Ribeiro, M., Hubert, L., Boddaert, N., Saudubray, J.-M., Robert, J.-J., Brunelle, F., Rahier, J., Jaubert, F., Nihoul-Fekete, C., de Lonlay, P. <strong>The Knudson's two-hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism.</strong> J. Clin. Endocr. Metab. 91: 4118-4123, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16882742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16882742</a>] [<a href="https://doi.org/10.1210/jc.2006-0397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16882742">Giurgea et al. (2006)</a> reported 3 patients with hyperinsulinemic hypoglycemia, all with paternally inherited SUR1 mutations. The first 2 patients both had 2 distinct foci of islet cell hyperplasia, and the third patient had a very large area of islet cell hyperplasia involving the major portion of the pancreas. In patients 1 and 2, haploinsufficiency for the maternal 11p15.5 region resulted from a somatic deletion specific for each of the focal lesions, as shown by the diversity of deletion breakpoints. In patient 3, an identical somatic maternal 11p15 deletion demonstrated by similar breakpoints was shown in 2 independent lesion samples, suggesting a very early event during pancreas embryogenesis. <a href="#12" class="mim-tip-reference" title="Giurgea, I., Sempoux, C., Bellanne-Chantelot, C., Ribeiro, M., Hubert, L., Boddaert, N., Saudubray, J.-M., Robert, J.-J., Brunelle, F., Rahier, J., Jaubert, F., Nihoul-Fekete, C., de Lonlay, P. <strong>The Knudson's two-hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism.</strong> J. Clin. Endocr. Metab. 91: 4118-4123, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16882742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16882742</a>] [<a href="https://doi.org/10.1210/jc.2006-0397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16882742">Giurgea et al. (2006)</a> concluded that individual patients with focal hyperinsulinism may have more than 1 focal pancreatic lesion due to separate somatic maternal deletion of the 11p15 region. These patients and those with solitary focal lesions may follow the 2-hit model described by Knudson. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16882742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#32" class="mim-tip-reference" title="Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A. <strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong> J. Clin. Invest. 118: 2877-2886, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18596924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18596924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18596924[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/10.1172/JCI35414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18596924">Pinney et al. (2008)</a> identified 14 different dominantly inherited K(ATP) channel mutations in 16 unrelated families, 13 with mutations in the ABCC8 gene (see, e.g., <a href="#0011">600509.0011</a>) and 3 with mutations in the KCNJ11 gene (see, e.g., <a href="/entry/600937#0020">600937.0020</a>). Unlike recessive mutations, dominantly inherited K(ATP) mutant subunits trafficked normally to the plasma membrane when expressed in simian kidney cells; dominant mutations also resulted in different channel-gating defects, with dominant ABCC8 mutations diminishing channel responses to magnesium adenosine diphosphate or diazoxide and dominant KCNJ11 mutations impairing channel opening even in the absence of nucleotides. <a href="#32" class="mim-tip-reference" title="Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A. <strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong> J. Clin. Invest. 118: 2877-2886, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18596924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18596924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18596924[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/10.1172/JCI35414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18596924">Pinney et al. (2008)</a> concluded that there are distinctive features of dominant K(ATP) hyperinsulinism compared to the more common and more severe recessive form, including retention of normal subunit trafficking, impaired channel activity, and a milder hypoglycemia phenotype that may escape detection in infancy and is often responsive to diazoxide medical therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18596924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#4" class="mim-tip-reference" title="Bellanne-Chantelot, C., Saint-Martin, C., Ribeiro, M.-J., Vaury, C., Verkarre, V., Arnoux, J.-B., Valayannopoulos, V., Gobrecht, S., Sempoux, C., Rahier, J., Fournet, J.-C., Jaubert, F., Aigrain, Y., Nihoul-Fekete, C., de Lonlay, P. <strong>ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.</strong> J. Med. Genet. 47: 752-759, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20685672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20685672</a>] [<a href="https://doi.org/10.1136/jmg.2009.075416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20685672">Bellanne-Chantelot et al. (2010)</a> analyzed the ABCC8 and KCNJ11 genes in 109 diazoxide-unresponsive patients with congenital hyperinsulinism and identified mutations in 89 (82%) of the probands. A total of 118 mutations were found, including 106 (90%) in ABCC8 and 12 (10%) in KCNJ11; 94 of the 118 were different mutations, and 41 had been previously reported. The 37 patients diagnosed with focal disease all had heterozygous mutations, whereas 30 (47%) of 64 patients known or suspected to have diffuse disease had homozygous or compound heterozygous mutations, 22 (34%) had a heterozygous mutation, and 12 (19%) had no mutation in the ABCC8 or KCNJ11 genes. The authors concluded that ABCC8 gene defects are the most important cause of diazoxide-unresponsive congenital hyperinsulinism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20685672" 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 29 patients with diazoxide-unresponsive hyperinsulinemic hypoglycemia, in whom direct sequencing revealed no mutation in the ABCC8 or KCNJ11 genes, or in whom a single recessively acting heterozygous ABCC8 mutation had been identified despite histologically confirmed diffuse pancreatic disease, <a href="#10" class="mim-tip-reference" title="Flanagan, S. E., Damhuis, A., Bannerjee, I., Rokicki, D., Jefferies, C., Kapoor, R. R., Hussain, K., Ellard, S. <strong>Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.</strong> Pediat. Diabetes 13: 285-289, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21978130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21978130</a>] [<a href="https://doi.org/10.1111/j.1399-5448.2011.00821.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21978130">Flanagan et al. (2012)</a> used multiplex ligation-dependent probe amplification (MPLA) for ABCC8 dosage analysis and identified 3 different partial gene deletions (see, e.g., <a href="#0027">600509.0027</a>) in 4 patients (14%). Two of the patients, who had diffuse disease, also carried another ABCC8 mutation that had previously been detected by sequence analysis (see, e.g., <a href="#0028">600509.0028</a>), whereas the 2 patients with focal disease carried only the deletion in ABCC8. Pancreatic tissue was not available from the latter 2 patients for loss-of-heterozygosity studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21978130" 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>
|
|
|
|
<div class="mim-changed mim-change"><p>In 5 patients with diazoxide-unresponsive focal hyperinsulinism in whom direct sequencing and MPLA dosage analysis failed to reveal a mutation in the ABCC8 or KCNJ11 genes, <a href="#11" class="mim-tip-reference" title="Flanagan, S. E., Xie, W., Caswell, R., Damhuis, A., Vianey-Saban, C., Akcay, T., Darendeliler, F., Bas, F., Guven, A., Siklar, Z., Ocal, G., Berberoglu, M., and 9 others. <strong>Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.</strong> Am. J. Hum. Genet. 92: 131-136, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23273570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23273570</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23273570[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/10.1016/j.ajhg.2012.11.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23273570">Flanagan et al. (2013)</a> performed next-generation sequencing of the entire genomic region of ABCC8 and identified heterozygosity for a paternally inherited deep intronic splicing variant (c.1333-1013A-G; <a href="#0029">600509.0029</a>). The variant was also identified in homozygosity in 1 patient with diffuse hyperinsulinism. Chromosome 11 microsatellite analysis revealed a shared haplotype among the 6 patients, 4 of whom were from Ireland, suggesting that the variant represents a founder mutation in the Irish population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23273570" 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></div>
|
|
|
|
<div class="mim-changed mim-change"><p><strong><em>Type 2 Diabetes Mellitus</em></strong>
|
|
</p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#16" class="mim-tip-reference" title="Goksel, D. L., Fischbach, K., Duggirala, R., Mitchell, B. D., Aguilar-Bryan, L., Blangero, J., Stern, M. P., O'Connell, P. <strong>Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.</strong> Hum. Genet. 103: 280-285, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9799081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9799081</a>] [<a href="https://doi.org/10.1007/s004390050817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9799081">Goksel et al. (1998)</a> found that a silent single-nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-AGA; arg1273 to arg) was strongly associated with insulin response to an oral glucose load in nondiabetic Mexican-American subjects. This observation prompted <a href="#35" class="mim-tip-reference" title="Reis, A. F., Ye, W.-Z., Dubois-Laforgue, D., Bellanne-Chantelot, C., Timsit, J., Velho, G. <strong>Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians.</strong> Hum. Genet. 107: 138-144, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030411</a>] [<a href="https://doi.org/10.1007/s004390000345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030411">Reis et al. (2000)</a> to investigate the possible association of this SNP with type 2 diabetes (T2D; see <a href="/entry/125853">125853</a>) in French Caucasian subjects. They observed an increased frequency of the A allele in patients compared with controls. This association was stronger in the subgroup of patients who were diagnosed at age 45 years or younger. Unexpectedly, the G allele was strongly associated with arterial hypertension in obese diabetic subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11030411+9799081" 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></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#23" class="mim-tip-reference" title="Laukkanen, O., Pihlajamaki, J., Lindstrom, J., Eriksson, J., Valle, T. T., Hamalainen, H., Ilanne-Patrikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J., Uusitupa, M., Laakso, M., Finnish Diabetes Prevention Study Group. <strong>Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.</strong> J. Clin. Endocr. Metab. 89: 6286-6290, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15579791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15579791</a>] [<a href="https://doi.org/10.1210/jc.2004-1204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15579791">Laukkanen et al. (2004)</a> investigated whether common polymorphisms in the ABCC8 and KCNJ11 genes were associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. The 1273AGA allele of the ABCC8 gene was associated with a 2-fold risk of type 2 diabetes (odds ratio (OR), 2.00; 95% CI, 1.19-3.36; P = 0.009). This silent polymorphism was in linkage disequilibrium with 3 promoter polymorphisms, and they formed a high-risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09-3.27; P = 0.023). Subjects with both the high-risk haplotype of the ABCC8 gene and the 23K allele of the KCNJ11 gene (see E23K, <a href="/entry/600937#0014">600937.0014</a>) had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). <a href="#23" class="mim-tip-reference" title="Laukkanen, O., Pihlajamaki, J., Lindstrom, J., Eriksson, J., Valle, T. T., Hamalainen, H., Ilanne-Patrikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J., Uusitupa, M., Laakso, M., Finnish Diabetes Prevention Study Group. <strong>Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.</strong> J. Clin. Endocr. Metab. 89: 6286-6290, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15579791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15579791</a>] [<a href="https://doi.org/10.1210/jc.2004-1204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15579791">Laukkanen et al. (2004)</a> concluded that polymorphisms of the ABCC8 gene predict the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with that of the E23K polymorphism of the KCNJ11 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15579791" 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></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#27" class="mim-tip-reference" title="Meirhaeghe, A., Helbecque, N., Cottel, D., Arveiler, D., Ruidavets, J.-B., Haas, B., Ferrieres, J., Tauber, J.-P., Bingham, A., Amouyel, P. <strong>Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study.</strong> Am. J. Med. Genet. 101: 4-8, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343328</a>] [<a href="https://doi.org/10.1002/ajmg.1297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343328">Meirhaeghe et al. (2001)</a> described an association study between type 2 diabetes and response to sulfonylurea therapy and a polymorphism of the SUR1 gene: IVS16-3T-C. They investigated 122 subjects in 3 French cities: Lille (in the north), Strasbourg (in the east), and Toulouse (in the south). The genotypes of 1,250 controls were in Hardy-Weinberg equilibrium as follows: TT 29%, TC 50%, and CC 21%. The frequency of the -3C allele was 0.46 in controls. In type 2 diabetes cases, the frequency of the C allele was 0.53. Subjects bearing at least one -3C allele and treated with sulfonylurea agents had fasting plasma triglyceride concentrations 35% lower than subjects who were TT homozygous, whereas no difference could be detected between genotypes in subjects with T2D treated with other medications. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343328" 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></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#24" class="mim-tip-reference" title="Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., Hirschhorn, J. N. <strong>Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease.</strong> Nature Genet. 33: 177-182, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12524541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12524541</a>] [<a href="https://doi.org/10.1038/ng1071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12524541">Lohmueller et al. (2003)</a> performed a metaanalysis of genetic association studies to evaluate the contribution of common variants with a susceptibility to common disease. They concluded that there are probably many common variants in the human genome with modest but real effects on common disease risk, and that studies using large samples will convincingly identify such variants. They analyzed 301 published studies covering 25 different reported associations. There was a large excess of studies replicating the first positive reports, inconsistent with the hypothesis of no true positive associations. This excess of replications could not be reasonably explained by publication bias and was concentrated among 11 of the 25 associations. The C/T SNP in exon 22 of the ABCC8 gene, which was first reported to show association of the T allele with type 2 diabetes (<a href="#22" class="mim-tip-reference" title="Inoue, H., Ferrer, J., Welling, C. M., Elbein, S. C., Hoffman, M., Mayorga, R., Warren-Perry, M., Zhang, Y., Millns, H., Turner, R., Province, M., Bryan, J., Permutt, M. A., Aguilar-Bryan, L. <strong>Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.</strong> Diabetes 45: 825-831, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8635661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8635661</a>] [<a href="https://doi.org/10.2337/diab.45.6.825" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8635661">Inoue et al., 1996</a>), was one of these. Another was association of a -3 T/C SNP in intron 24, with C showing association with type 2 diabetes, reported also by <a href="#22" class="mim-tip-reference" title="Inoue, H., Ferrer, J., Welling, C. M., Elbein, S. C., Hoffman, M., Mayorga, R., Warren-Perry, M., Zhang, Y., Millns, H., Turner, R., Province, M., Bryan, J., Permutt, M. A., Aguilar-Bryan, L. <strong>Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.</strong> Diabetes 45: 825-831, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8635661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8635661</a>] [<a href="https://doi.org/10.2337/diab.45.6.825" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8635661">Inoue et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8635661+12524541" 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></div>
|
|
|
|
<p><strong><em>Permanent Neonatal Diabetes Mellitus 3</em></strong>
|
|
</p>
|
|
|
|
<p>In a 27-year-old man who had permanent neonatal diabetes (PNDM3; <a href="/entry/618857">618857</a>) with severe developmental delay and generalized epileptiform activity on EEG, a triad referred to as DEND, <a href="#34" class="mim-tip-reference" title="Proks, P., Arnold, A. L., Bruining, J., Girard, C., Flanagan, S. E., Larkin, B., Colclough, K., Hattersley, A. T., Ashcroft, F. M., Ellard, S. <strong>A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.</strong> Hum. Molec. Genet. 15: 1793-1800, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16613899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16613899</a>] [<a href="https://doi.org/10.1093/hmg/ddl101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16613899">Proks et al. (2006)</a> identified heterozygosity for a de novo missense mutation (F132L; <a href="#0016">600509.0016</a>) in the ABCC8 gene. Functional studies showed that F132L markedly reduced the sensitivity of the K(ATP) channel to inhibition by MgATP, thereby increasing the whole-cell K(ATP) current; the authors noted that the functional consequence of the F132L mutation mirrors that of KCNJ11 mutations causing neonatal diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16613899" 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>
|
|
|
|
<div class="mim-changed mim-change"><p>From a group of 73 patients with neonatal diabetes, <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> screened the ABCC8 gene in 34 who did not have alterations in chromosome 6q or mutations in the KCNJ11 or GCK (<a href="/entry/138079">138079</a>) genes. In 2 patients with permanent neonatal diabetes, they identified heterozygosity for a mutation (<a href="#0017">600509.0017</a> and <a href="#0018">600509.0018</a>, respectively). They also identified heterozygosity for 5 different mutations (see, e.g., <a href="#0019">600509.0019</a>-<a href="#0020">600509.0020</a>) in 7 patients with transient neonatal diabetes (see <a href="/entry/610374">610374</a>). Mutant channels in intact cells and in physiologic concentrations of magnesium ATP had markedly higher activity than did wildtype channels. These overactive channels remained sensitive to sulfonylurea, and treatment with sulfonylureas resulted in euglycemia. The mutation-positive fathers of 5 of the probands with transient neonatal diabetes developed type 2 diabetes mellitus (<a href="/entry/125853">125853</a>) in adulthood; <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> proposed that mutations of the ABCC8 gene may give rise to a monogenic form of type 2 diabetes with variable expression and age at onset. The authors noted that dominant mutations in ABCC8 accounted for 12% of cases of neonatal diabetes in the study group. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885549" 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></div>
|
|
|
|
<p><a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a> studied a cohort of 59 patients with permanent neonatal diabetes who received a diagnosis before 6 months of age and who did not have a mutation in KCNJ11 (<a href="/entry/600937">600937</a>). ABCC8 gene mutations were identified in 16 of the 59 patients (see, e.g., <a href="#0021">600509.0021</a>-<a href="#0026">600509.0026</a>), including 8 patients with heterozygous de novo mutations. The other 8 patients carried homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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>In a rat model of ischemic stroke (<a href="/entry/601367">601367</a>), <a href="#37" class="mim-tip-reference" title="Simard, J. M., Chen, M., Tarasov, K. V., Bhatta, S., Ivanova, S., Melnitchenko, L., Tsymbalyuk, N., West, G. A., Gerzanich, V. <strong>Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.</strong> Nature Med. 12: 433-440, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16550187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16550187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16550187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm1390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16550187">Simard et al. (2006)</a> found upregulation of Sur1 expression in ischemic neurons, astrocytes, and capillaries. Upregulation of Sur1 was linked to activation of the transcription factor Sp1 (<a href="/entry/189906">189906</a>) and was associated with expression of functional nonselective cation channels, which they called the NC(Ca-ATP) channel, but not K(ATP) channels. Treatment with low-dose glibenclamide, which blocks Sur1 and the NC(Ca-ATP) channel, reduced cerebral edema, infarct volume, and mortality by 50%. <a href="#37" class="mim-tip-reference" title="Simard, J. M., Chen, M., Tarasov, K. V., Bhatta, S., Ivanova, S., Melnitchenko, L., Tsymbalyuk, N., West, G. A., Gerzanich, V. <strong>Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.</strong> Nature Med. 12: 433-440, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16550187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16550187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16550187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm1390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16550187">Simard et al. (2006)</a> concluded that the NC(Ca-ATP) channel is involved in the development of cerebral edema and that targeting Sur1 may provide a new therapeutic approach to stroke. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16550187" 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>29 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/600509" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600509[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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, IVS, G-A, -1, EXON CHI DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009654 OR RCV001040039 OR RCV001260357 OR RCV001826455 OR RCV003466843" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009654, RCV001040039, RCV001260357, RCV001826455, RCV003466843" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009654...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a child with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), born of consanguineous parents, <a href="#39" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J. <strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Science 268: 426-429, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>] [<a href="https://doi.org/10.1126/science.7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716548">Thomas et al. (1995)</a> showed that a cloned pancreatic cDNA product had a 109-bp deletion within the NBF2 region of SUR, which corresponded to skipping of exon chi. The deletion caused disruption of the NBF2 consensus sequence by generating a frameshift and ultimately a premature stop signal 24 codons past the deletion. In genomic DNA, a homozygous G-to-A point mutation was found in the 3-prime end of the skipped exon. The recognition site for the restriction endonuclease MspI was destroyed by this base change. Both affected children in the family were homozygous, whereas the parents and 2 unaffected sibs were heterozygous. Twelve other affected children from 6 families of Saudi Arabian origin and 1 family of German origin were homozygous for the G-to-A point mutation, as demonstrated by loss of the MspI recognition site. The G-to-A mutation involved the last nucleotide of the skipped exon. <a href="#39" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J. <strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Science 268: 426-429, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>] [<a href="https://doi.org/10.1126/science.7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716548">Thomas et al. (1995)</a> cited other instances in which G-to-A point mutations at this position had been observed to result in skipping of the exon containing the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716548" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, IVS32, G-A, -9, EXON ALPHA DEL
|
|
</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> rs151344623 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs151344623;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/rs151344623?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=rs151344623" 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=rs151344623" 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=RCV000009656 OR RCV000144995 OR RCV000590487 OR RCV001267446 OR RCV001277185 OR RCV002467491 OR RCV003473069 OR RCV004532316 OR RCV005049326" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009656, RCV000144995, RCV000590487, RCV001267446, RCV001277185, RCV002467491, RCV003473069, RCV004532316, RCV005049326" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009656...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), born of consanguineous parents, <a href="#39" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J. <strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Science 268: 426-429, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>] [<a href="https://doi.org/10.1126/science.7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716548">Thomas et al. (1995)</a> found a mutation in the 3-prime splice site sequence preceding the NBF2 region. The G-to-A mutation destroyed an NciI restriction endonuclease recognition site, and homozygous loss of this site cosegregated with disease phenotype within the family. The G-to-A transition occurred at the ninth nucleotide from the 3-prime end of the intron preceding exon alpha, the first NBF2 exon. In a construct containing the mutation, 3 cryptic 3-prime splice sites within exon alpha were used in place of the wildtype splicing site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A. <strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong> Hum. Molec. Genet. 5: 1813-1822, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923011">Nestorowicz et al. (1996)</a> demonstrated that this mutation in the SUR1 gene and the F1388del mutation (<a href="#0006">600509.0006</a>) account for approximately 88% of hyperinsulinism-associated chromosomes in Ashkenazi Jewish patients. Haplotype analysis with microsatellite markers flanking the gene revealed that the delF1388 mutation, reported only in Ashkenazi probands, occurred on 2 related extended haplotypes. By contrast, the second, more common mutation (3992-9G-A) was associated with 9 different intergenic haplotypes and was reported in non-Jewish hyperinsulinism patients as well. <a href="#14" class="mim-tip-reference" title="Glaser, B., Furth, J., Stanley, C. A., Baker, L., Thornton, P. S., Landau, H., Permutt, M. A. <strong>Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.</strong> Hum. Mutat. 14: 23-29, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447255</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<23::AID-HUMU3>3.0.CO;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447255">Glaser et al. (1999)</a> evaluated disease-associated chromosomes from 41 Ashkenazi Jewish and 2 non-Jewish hyperinsulinism patients carrying the 3992-9G-A mutation by assessing haplotypes defined by 9 common single-nucleotide polymorphisms (SNPs), 6 in the SUR1 gene and 3 in the closely linked KIR6.2 gene. They found that all 54 chromosomes carrying this particular mutation in the Jewish patients appeared to have originated from 1 founder mutation, whereas the same mutation in chromosomes from non-Jewish patients originated independently. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8923011+10447255" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, GLY716VAL
|
|
</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> rs72559723 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72559723;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/rs72559723?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=rs72559723" 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=rs72559723" 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=RCV000009655 OR RCV000077845" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009655, RCV000077845" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009655...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), born of consanguineous Malaysian parents, <a href="#40" class="mim-tip-reference" title="Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J. <strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Am. J. Hum. Genet. 59: 510-518, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751851</a>]" pmid="8751851">Thomas et al. (1996)</a> found that the 6 exons that compose the NBF2 region of SUR had wildtype sequence. The NBF1 region, which is encoded by 8 exons that span approximately 8.2 kb of genomic sequence, shows strong homology with the NBF2 region and the NBF regions of other superfamily members. In of the proband of this family, a homozygous G-to-T transversion was found in the second exon (106-bp exon) of the NBF1 region. The point mutation was predicted to substitute a valine for the second glycine residue, G716V, of the Walker A motif of the NBF1 region, thereby altering a site that is conserved among all members of the ATP-binding-cassette superfamily. The mutation resulted in the loss of a BbvI restriction site allowing demonstration that the affected child was homozygous for the mutation, the parents heterozygous, and an unaffected sib homozygous for the wildtype allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8751851" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, IVS, G-A, -1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1564905676 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564905676;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=rs1564905676" 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=rs1564905676" 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=RCV000009658 OR RCV001328359 OR RCV002251422 OR RCV002251423" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009658, RCV001328359, RCV002251422, RCV002251423" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009658...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), born of nonconsanguineous German parents, <a href="#40" class="mim-tip-reference" title="Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J. <strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Am. J. Hum. Genet. 59: 510-518, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751851</a>]" pmid="8751851">Thomas et al. (1996)</a> identified compound heterozygosity for 2 mutations located in sequences predicted to affect RNA processing of the SUR transcript. The first mutation was a G-to-A transition located at the -1 residue, within the 3-prime splice site of the fifth exon (99-bp exon) of the NBF1 region. The transition destroyed a BstNI restriction site. A G-to-A mutation in the -1 invariant residue in the 3-prime splice site in other genes has been found to result in 100% skipping of the involved exon or in both exon skipping and cryptic 3-prime splice site activation. The second mutation was a branch point mutation (<a href="#0005">600509.0005</a>) at nucleotide -20 of the 146-bp exon preceding the NBF1 encoding region. The presence of this point mutation disrupted an invariant A residue of the branch-point consensus. This A-to-G change resulted in the destruction of an engineered SpeI restriction endonuclease site. Restriction analysis demonstrated that the first mutant allele was of maternal origin and the second of paternal origin. An unaffected brother was homozygous for the wildtype alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8751851" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, BRANCH POINT, A-G, -20
|
|
</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> rs931436550 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs931436550;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/rs931436550?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=rs931436550" 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=rs931436550" 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=RCV000009659 OR RCV001851768 OR RCV002266898 OR RCV002266899 OR RCV003460445 OR RCV004525849" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009659, RCV001851768, RCV002266898, RCV002266899, RCV003460445, RCV004525849" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009659...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the branch point mutation in the ABCC8 gene that was found in compound heterozygous state in patients with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>) by <a href="#40" class="mim-tip-reference" title="Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J. <strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Am. J. Hum. Genet. 59: 510-518, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751851</a>]" pmid="8751851">Thomas et al. (1996)</a>, see <a href="#0004">600509.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8751851" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, 3-BP DEL, PHE1388DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs151344624 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs151344624;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=rs151344624" 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=rs151344624" 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=RCV000177757 OR RCV000201913 OR RCV000587070 OR RCV001277181 OR RCV002243861 OR RCV003462282 OR RCV004537448 OR RCV005042381" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000177757, RCV000201913, RCV000587070, RCV001277181, RCV002243861, RCV003462282, RCV004537448, RCV005042381" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000177757...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Ashkenazi Jewish families with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), <a href="#29" class="mim-tip-reference" title="Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A. <strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong> Hum. Molec. Genet. 5: 1813-1822, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923011">Nestorowicz et al. (1996)</a> identified a 3-bp deletion in exon 34 of the SUR gene, resulting in deletion of phenylalanine-1388. The deletion was associated with a specific haplotype (H1) in the D11S1901-D11S1310 region. The mutation led to the generation of a novel BseR1 restriction site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923011" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, EX35, G-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> rs387906407 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906407;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/rs387906407?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=rs387906407" 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=rs387906407" 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=RCV000009654 OR RCV001040039 OR RCV001260357 OR RCV001826455 OR RCV003466843" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009654, RCV001040039, RCV001260357, RCV001826455, RCV003466843" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009654...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Dunne, M. J., Kane, C., Shepherd, R. M., Sanchez, J. A., James, R. F. L., Johnson, P. R. V., Aynsley-Green, A., Lu, S., Clement, J. P., IV, Lindley, K. J., Seino, S., Aguilar-Bryan, L. <strong>Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor.</strong> New Eng. J. Med. 336: 703-706, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9041101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9041101</a>] [<a href="https://doi.org/10.1056/NEJM199703063361005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9041101">Dunne et al. (1997)</a> identified a G-to-A transition in the terminal nucleotide of exon 35 of the SUR gene in homozygous state in a child from consanguineous Saudi Arabian parents. The child and 2 sibs had persistent hyperinsulinemic hypoglycemia of infancy (HHF1; <a href="/entry/256450">256450</a>). The 2 affected sibs had undergone partial pancreatectomy for the disorder. The proband was born at term after a normal gestation, weighed 4.25 kg, and had macrosomia and plethora, features of in utero hyperinsulinism. Two partial pancreatectomies were required for control of hypoglycemia. Histologic examination of the pancreas revealed diffuse nesidioblastosis. The parents were heterozygous for the G-A mutation. (The mutations previously discovered by Thomas et al. (<a href="#39" class="mim-tip-reference" title="Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J. <strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Science 268: 426-429, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>] [<a href="https://doi.org/10.1126/science.7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7716548">1995</a>, <a href="#40" class="mim-tip-reference" title="Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J. <strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong> Am. J. Hum. Genet. 59: 510-518, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751851</a>]" pmid="8751851">1996</a>) and by <a href="#29" class="mim-tip-reference" title="Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A. <strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong> Hum. Molec. Genet. 5: 1813-1822, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923011">Nestorowicz et al. (1996)</a> were not mentioned by <a href="#7" class="mim-tip-reference" title="Dunne, M. J., Kane, C., Shepherd, R. M., Sanchez, J. A., James, R. F. L., Johnson, P. R. V., Aynsley-Green, A., Lu, S., Clement, J. P., IV, Lindley, K. J., Seino, S., Aguilar-Bryan, L. <strong>Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor.</strong> New Eng. J. Med. 336: 703-706, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9041101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9041101</a>] [<a href="https://doi.org/10.1056/NEJM199703063361005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9041101">Dunne et al. (1997)</a>.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8923011+7716548+9041101+8751851" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ARG1353PRO
|
|
</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> rs28936370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936370;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/rs28936370?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=rs28936370" 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=rs28936370" 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=RCV000009662 OR RCV001851769 OR RCV002504772" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009662, RCV001851769, RCV002504772" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009662...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of persistent hyperinsulinemic hypoglycemia of infancy (HHF1; <a href="/entry/256450">256450</a>) due to focal adenomatous hyperplasia, <a href="#44" class="mim-tip-reference" title="Verkarre, V., Fournet, J.-C., de Lonlay, P., Gross-Morand, M.-S., Devillers, M., Rahier, J., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C. <strong>Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.</strong> J. Clin. Invest. 102: 1286-1291, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9769320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9769320</a>] [<a href="https://doi.org/10.1172/JCI4495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9769320">Verkarre et al. (1998)</a> found a 4058G-C transversion in exon 33 of the paternally derived SUR gene, leading to an arg1353-to-pro (R1353P) amino acid substitution. The father was constitutionally heterozygous for the same mutation. This was 1 of 12 cases in which loss of maternal alleles of the 11p15 chromosomal region had been found, limited to the hyperplastic lesions of focal adenomatous hyperplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9769320" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ARG1421CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28938469 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28938469;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=rs28938469" 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=rs28938469" 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=RCV000009663 OR RCV001235181 OR RCV001831557 OR RCV003473070 OR RCV005042018" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009663, RCV001235181, RCV001831557, RCV003473070, RCV005042018" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009663...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a sporadic case of persistent hyperinsulinemic hypoglycemia of infancy (HHF1; <a href="/entry/256450">256450</a>) due to focal adenomatous hyperplasia, <a href="#44" class="mim-tip-reference" title="Verkarre, V., Fournet, J.-C., de Lonlay, P., Gross-Morand, M.-S., Devillers, M., Rahier, J., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C. <strong>Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.</strong> J. Clin. Invest. 102: 1286-1291, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9769320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9769320</a>] [<a href="https://doi.org/10.1172/JCI4495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9769320">Verkarre et al. (1998)</a> found a 4261C-T transition in exon 35 of the paternally-derived SUR gene, leading to an arg1421-to-cys (R1421C) amino acid substitution. The father was constitutionally heterozygous for the same mutation. This was 1 of 12 cases in which loss of maternal alleles of the 11p15 chromosomal region had been found, limited to the hyperplastic lesions of focal adenomatous hyperplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9769320" 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></div>
|
|
|
|
<p><a href="#26" class="mim-tip-reference" title="Matsuo, M., Trapp, S., Tanizawa, Y., Kioka, N., Amachi, T., Oka, Y., Ashcroft, F. M., Ueda, K. <strong>Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy.</strong> J. Biol. Chem. 275: 41184-41191, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10993895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10993895</a>] [<a href="https://doi.org/10.1074/jbc.M006503200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10993895">Matsuo et al. (2000)</a> analyzed the functional consequences of the R1421C mutation, which they referred to as R1420C. They showed that the mutation lowers the affinity of the nucleotide-binding fold 2 (NBF2) for ATP and ADP and abolishes the ability of nucleotide binding at NBF2 to stabilize 8-azido-ATP binding at NBF1. In addition, the mutation decreases the expression of potassium-ATP channels, and a smaller current in R1420C-PHHI beta cells leads to enhanced insulin secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10993895" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ARG1494TRP
|
|
</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> rs28936371 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936371;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/rs28936371?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=rs28936371" 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=rs28936371" 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=RCV000009664 OR RCV000710390 OR RCV001831558 OR RCV003466844 OR RCV004549354 OR RCV005042019" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009664, RCV000710390, RCV001831558, RCV003466844, RCV004549354, RCV005042019" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009664...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated sporadic cases of persistent hyperinsulinemic hypoglycemia of infancy (HHF1; <a href="/entry/256450">256450</a>) due to focal adenomatous hyperplasia, <a href="#44" class="mim-tip-reference" title="Verkarre, V., Fournet, J.-C., de Lonlay, P., Gross-Morand, M.-S., Devillers, M., Rahier, J., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C. <strong>Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.</strong> J. Clin. Invest. 102: 1286-1291, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9769320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9769320</a>] [<a href="https://doi.org/10.1172/JCI4495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9769320">Verkarre et al. (1998)</a> demonstrated loss of heterozygosity of the 11p15 region in the maternal allele and a point mutation in the paternally derived SUR allele: a 4480C-T transition in exon 37 leading to an arg1494-to-trp (R1494W) substitution. The father in each case was heterozygous for the R1494W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9769320" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, GLU1506LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852671;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=rs137852671" 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=rs137852671" 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=RCV000009665 OR RCV000201911" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009665, RCV000201911" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009665...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Finnish family with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), <a href="#20" class="mim-tip-reference" title="Huopio, H., Reimann, F., Ashfield, R., Komulainen, J., Lenko, H.-L., Rahier, J., Vauhkonen, I., Kere, J., Laakso, M., Ashcroft, F., Otonkoski, T. <strong>Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.</strong> J. Clin. Invest. 106: 897-906, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11018078[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/10.1172/JCI9804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11018078">Huopio et al. (2000)</a> identified a heterozygous glu1506-to-lys (E1506K) mutation in the ABCC8 gene. This mutation led to a reduction, but not a complete loss, of K(ATP) channel activity. <a href="#19" class="mim-tip-reference" title="Huopio, H., Otonkoski, T., Vauhkonen, I., Reimann, F., Ashcroft, F. M., Laakso, M. <strong>A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. (Commentary)</strong> Lancet 361: 301-307, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12559865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12559865</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)12325-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12559865">Huopio et al. (2003)</a> characterized glucose metabolism in adults heterozygous for this mutation. They found that the mutation results in congenital hyperinsulinism in infancy, loss of insulin secretory capacity in early adulthood, and diabetes in middle age. <a href="#19" class="mim-tip-reference" title="Huopio, H., Otonkoski, T., Vauhkonen, I., Reimann, F., Ashcroft, F. M., Laakso, M. <strong>A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. (Commentary)</strong> Lancet 361: 301-307, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12559865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12559865</a>] [<a href="https://doi.org/10.1016/S0140-6736(03)12325-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12559865">Huopio et al. (2003)</a> suggested that the disorder represents a new subtype of autosomal dominant diabetes. They noted that, except for age at presentation, the E1506K mutation causes a disorder that fulfills the criteria for a form of MODY (see <a href="/entry/606391">606391</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11018078+12559865" 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 6-year-old girl who was macrosomic at birth and had hyperinsulinemic hypoglycemia, <a href="#32" class="mim-tip-reference" title="Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A. <strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong> J. Clin. Invest. 118: 2877-2886, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18596924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18596924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18596924[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/10.1172/JCI35414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18596924">Pinney et al. (2008)</a> identified heterozygosity for what they designated the E1507K mutation in the ABCC8 gene. (<a href="#32" class="mim-tip-reference" title="Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A. <strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong> J. Clin. Invest. 118: 2877-2886, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18596924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18596924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18596924[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/10.1172/JCI35414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18596924">Pinney et al., 2008</a> stated that they used numbering that included the alternatively spliced exon 17 sequence, and therefore the E1506K mutation reported by <a href="#20" class="mim-tip-reference" title="Huopio, H., Reimann, F., Ashfield, R., Komulainen, J., Lenko, H.-L., Rahier, J., Vauhkonen, I., Kere, J., Laakso, M., Ashcroft, F., Otonkoski, T. <strong>Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.</strong> J. Clin. Invest. 106: 897-906, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11018078[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/10.1172/JCI9804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11018078">Huopio et al., 2000</a> is the same amino acid change as the E1507K mutation reported here.) <a href="#32" class="mim-tip-reference" title="Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A. <strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong> J. Clin. Invest. 118: 2877-2886, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18596924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18596924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18596924[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/10.1172/JCI35414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18596924">Pinney et al. (2008)</a> identified the E1507K in 8 other members of the family, none of whom had been suspected of having hypoglycemia, although 3 had severe symptoms, and 3 had mild symptoms consistent with hypoglycemia. The proband's mother and younger brother were the only mutation carriers who denied ever having symptoms of hypoglycemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11018078+18596924" 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 LEUCINE-SENSITIVE HYPOGLYCEMIA OF INFANCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ARG1353HIS
|
|
</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> rs28936370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936370;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/rs28936370?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=rs28936370" 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=rs28936370" 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=RCV000009666 OR RCV001851770 OR RCV003466845 OR RCV005042020" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009666, RCV001851770, RCV003466845, RCV005042020" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009666...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old boy with leucine-sensitive hypoglycemia (LIH; <a href="/entry/240800">240800</a>), <a href="#25" class="mim-tip-reference" title="Magge, S. N., Shyng, S.-L., MacMullen, C., Steinkrauss, L., Ganguly, A., Katz, L. E. L., Stanley, C. A. <strong>Familial leucine-sensitive hypoglycemia in infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.</strong> J. Clin. Endocr. Metab. 89: 4450-4456, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15356046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15356046</a>] [<a href="https://doi.org/10.1210/jc.2004-0441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15356046">Magge et al. (2004)</a> identified a 4058G-A transition in exon 33 of the SUR1 gene that resulted in an arg1353-to-his (R1353H) substitution. Arg1353 of SUR1 is conserved across golden hamster, European hamster, rat, mouse, fruit fly, and cricket and is also conserved between human SUR1 and isoforms of SUR2 (<a href="/entry/601439">601439</a>). Rubidium ion efflux assay and electrophysiologic studies of R1353H SUR1 coexpressed with wildtype Kir6.2 (<a href="/entry/600937">600937</a>) in simian kidney fibroblasts demonstrated partially impaired ATP-dependent potassium channel function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15356046" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, VAL187ASP
|
|
</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> rs137852672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852672;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/rs137852672?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=rs137852672" 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=rs137852672" 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=RCV000009667 OR RCV000723825 OR RCV003473071 OR RCV005042021" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009667, RCV000723825, RCV003473071, RCV005042021" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009667...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 15 of 24 Finnish patients with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), <a href="#30" class="mim-tip-reference" title="Otonkoski, T., Ammala, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K., Ashfield, R., Huang, E., Komulainen, J., Ashcroft, F. M., Dunne, M. J., Kere, J., Thomas, P. M. <strong>A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.</strong> Diabetes 48: 408-415, and 415, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10334322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10334322</a>] [<a href="https://doi.org/10.2337/diabetes.48.2.408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10334322">Otonkoski et al. (1999)</a> identified homozygosity or heterozygosity for a 560T-A transversion in exon 4 of the ABCC8 gene, resulting in a val187-to-asp (V187D) substitution located toward the cytosolic end of the putative fourth or fifth transmembrane domain. In vitro studies demonstrated that the presence of the V187D mutation renders the potassium channel completely nonfunctional. Parents and sibs who were carriers of the mutation were apparently asymptomatic; <a href="#30" class="mim-tip-reference" title="Otonkoski, T., Ammala, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K., Ashfield, R., Huang, E., Komulainen, J., Ashcroft, F. M., Dunne, M. J., Kere, J., Thomas, P. M. <strong>A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.</strong> Diabetes 48: 408-415, and 415, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10334322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10334322</a>] [<a href="https://doi.org/10.2337/diabetes.48.2.408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10334322">Otonkoski et al. (1999)</a> postulated the presence of another mutation in heterozygous affected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10334322" 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 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, 3-BP DEL, SER1387DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906408 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906408;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=rs387906408" 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=rs387906408" 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=RCV000009668 OR RCV000516204 OR RCV002243632 OR RCV002243633" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009668, RCV000516204, RCV002243632, RCV002243633" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009668...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of the 3-generation family (family 1) with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>) originally reported by <a href="#42" class="mim-tip-reference" title="Thornton, P. S., Satin-Smith, M. S., Herold, K., Glaser, B., Chiu, K. C., Nestorowicz, A., Permutt, M. A., Baker, L., Stanley, C. A. <strong>Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.</strong> J. Pediat. 132: 9-14, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9469993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9469993</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70477-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9469993">Thornton et al. (1998)</a>, <a href="#41" class="mim-tip-reference" title="Thornton, P. S., MacMullen, C., Ganguly, A., Ruchelli, E., Steinkrauss, L., Crane, A., Aguilar-Bryan, L., Stanley, C. A. <strong>Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.</strong> Diabetes 52: 2403-2410, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12941782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12941782</a>] [<a href="https://doi.org/10.2337/diabetes.52.9.2403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12941782">Thornton et al. (2003)</a> identified heterozygosity for a 3-bp deletion (4159-4161) in exon 34 of the ABCC8 gene, resulting in an in-frame deletion of a serine at codon 1387 (ser1387del). The mutation was not found in 4 unaffected family members. Studies in COSm6 cells revealed that potassium channels containing the mutation were not functional. <a href="#41" class="mim-tip-reference" title="Thornton, P. S., MacMullen, C., Ganguly, A., Ruchelli, E., Steinkrauss, L., Crane, A., Aguilar-Bryan, L., Stanley, C. A. <strong>Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.</strong> Diabetes 52: 2403-2410, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12941782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12941782</a>] [<a href="https://doi.org/10.2337/diabetes.52.9.2403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12941782">Thornton et al. (2003)</a> noted that this mutation is immediately adjacent to the F1388del (<a href="#0006">600509.0006</a>) mutation that causes recessive hyperinsulinism in Ashkenazi Jews. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12941782+9469993" 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="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, -64C-G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1395224084 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1395224084;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=rs1395224084" 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=rs1395224084" 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=RCV000009669 OR RCV001851771 OR RCV002254260 OR RCV002254261 OR RCV004734507 OR RCV005042022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009669, RCV001851771, RCV002254260, RCV002254261, RCV004734507, RCV005042022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009669...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant of Spanish descent diagnosed 3 days postnatally with hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), <a href="#43" class="mim-tip-reference" title="Tornovsky, S., Crane, A., Cosgrove, K. E., Hussain, K., Lavie, J., Heyman, M., Nesher, Y., Kuchinski, N., Ben-Shushan, E., Shatz, O., Nahari, E., Potikha, T., and 11 others. <strong>Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.</strong> J. Clin. Endocr. Metab. 89: 6224-6234, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15579781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15579781</a>] [<a href="https://doi.org/10.1210/jc.2004-1233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15579781">Tornovsky et al. (2004)</a> identified heterozygosity for a -64C-G transversion in the promoter of the ABCC8 gene on the paternal allele. Functional studies using a luciferase reporter vector revealed a 40% decrease in reporter gene expression for the mutant variant compared to wildtype, and the variant was not found in 100 control chromosomes tested. No mutation was found on the maternal allele. No focal lesion had been identified after near-total pancreatectomy, but the specimen was not available for reevaluation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15579781" 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="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 DIABETES MELLITUS, PERMANENT NEONATAL, 3, WITH NEUROLOGIC FEATURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, PHE132LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356637 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356637;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=rs80356637" 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=rs80356637" 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=RCV000009670 OR RCV000020286 OR RCV001851772 OR RCV002051781" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009670, RCV000020286, RCV001851772, RCV002051781" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009670...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 27-year-old man who had permanent neonatal diabetes (PNDM3; <a href="/entry/618857">618857</a>) with severe developmental delay and generalized epileptiform activity on EEG, <a href="#34" class="mim-tip-reference" title="Proks, P., Arnold, A. L., Bruining, J., Girard, C., Flanagan, S. E., Larkin, B., Colclough, K., Hattersley, A. T., Ashcroft, F. M., Ellard, S. <strong>A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.</strong> Hum. Molec. Genet. 15: 1793-1800, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16613899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16613899</a>] [<a href="https://doi.org/10.1093/hmg/ddl101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16613899">Proks et al. (2006)</a> identified heterozygosity for a de novo 394T-C transition in exon 3 of the ABCC8 gene, resulting in a phe132-to-leu (F132L) substitution. The mutation was not found in his unaffected parents or in 150 normal chromosomes. The authors considered the phenotype in this patient to be a case of DEND (developmental delay, epilepsy, and neonatal diabetes). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16613899" 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="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 DIABETES MELLITUS, PERMANENT NEONATAL, 3, WITH NEUROLOGIC FEATURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, LEU213ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356642 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356642;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=rs80356642" 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=rs80356642" 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=RCV000009671 OR RCV001089457" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009671, RCV001089457" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009671...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-year-old boy (family 12) with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>) and neurologic features, <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> identified heterozygosity for a de novo leu213-to-arg (L213R) substitution. The patient's parents reported that he had motor and developmental delays, which were subsequently documented to include dyspraxia. He did not have seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885549" 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="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ILE1424VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356653 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356653;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=rs80356653" 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=rs80356653" 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=RCV000009672 OR RCV001089458" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009672, RCV001089458" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009672...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient (family 16) with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>), <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> identified heterozygosity for a de novo ile1424-to-val (I1424V) substitution. This patient did not have abnormal cognitive function or development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885549" 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="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 DIABETES MELLITUS, TRANSIENT NEONATAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change">TYPE 2 DIABETES MELLITUS, INCLUDED</div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ARG1379CYS
|
|
</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> rs137852673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852673;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/rs137852673?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=rs137852673" 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=rs137852673" 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=RCV000009673 OR RCV000009674 OR RCV000502425 OR RCV001249022 OR RCV001851773 OR RCV004734508" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009673, RCV000009674, RCV000502425, RCV001249022, RCV001851773, RCV004734508" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009673...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a French girl (family 19) with transient neonatal diabetes mellitus (TNDM2; <a href="/entry/610374">610374</a>) who had a recurrence of diabetes at age 6 and in affected members of an unrelated 5-generation French family (family 17) with transient neonatal diabetes and adult-onset type 2 diabetes mellitus (T2D; <a href="/entry/125853">125853</a>), <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> identified heterozygosity for an arg1379-to-cys (R1379C) substitution. The mutation arose de novo in the first patient. The 5-year-old female proband of the family had transient neonatal diabetes. Her father developed diabetes at age 32 that was treated with sulfonylureas, and her paternal grandmother was diagnosed with gestational diabetes and treated with diet, and a paternal great-aunt was diagnosed at age 44 with diabetes that was also treated with sulfonylureas. <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type 2 diabetes with variable expression and age at onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885549" 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></div>
|
|
|
|
<p><a href="#6" class="mim-tip-reference" title="de Wet, H., Rees, M. G., Shimomura, K., Aittoniemi, J., Patch, A.-M., Flanagan, S. E., Ellard, S., Hattersley, A. T., Sansom, M. S. P., Ashcroft, F. M. <strong>Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.</strong> Proc. Nat. Acad. Sci. 104: 18988-18992, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18025464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18025464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18025464[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0707428104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18025464">De Wet et al. (2007)</a> performed functional studies of this mutation, which they designated R1380C, and demonstrated enhanced MgATP hydrolysis by purified isolated fusion proteins of maltose-binding protein and the second nucleotide-binding domain of ABCC8, in which the mutation is located. This increase in ATPase activity reduced the sensitivity of the channel to inhibition by MgATP and increased the whole-cell K(ATP) current. The authors noted that in pancreatic beta cells, such an increase in K(ATP) current would be expected to impair insulin secretion and thereby cause diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18025464" 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="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 DIABETES MELLITUS, TRANSIENT NEONATAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change">TYPE 2 DIABETES MELLITUS, INCLUDED</div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, LEU582VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852674 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852674;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=rs137852674" 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=rs137852674" 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=RCV000009675 OR RCV000009676" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009675, RCV000009676" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009675...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a 2-year-old French boy (family 36) with transient neonatal diabetes mellitus (TNDM2; <a href="/entry/610374">610374</a>) and in affected members of an unrelated 3-generation French family (family 16) with transient neonatal diabetes and adult-onset type 2 diabetes mellitus (T2D; <a href="/entry/125853">125853</a>), <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> identified heterozygosity for a leu583-to-val (L582V) substitution. The mutation arose de novo in the first patient. In the affected family, the 5-year-old male proband and his female cousin had transient neonatal diabetes, whereas their mutation-positive fathers both developed after age 30 adult-onset type 2 diabetes that was treated with diet alone; and their paternal grandfather also had type 2 diabetes occurring later in life. <a href="#2" class="mim-tip-reference" title="Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. <strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong> New Eng. J. Med. 355: 456-466, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>] [<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885549">Babenko et al. (2006)</a> proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type 2 diabetes with variable expression and age at onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885549" 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></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ASN72SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356634 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356634;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=rs80356634" 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=rs80356634" 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=RCV000009677 OR RCV001089459 OR RCV003473072" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009677, RCV001089459, RCV003473072" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009677...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient from a cohort of 59 patients with permanent neonatal diabetes (PNDM3; <a href="/entry/618857">618857</a>) who received a diagnosis before 6 months of age and who did not have a KCNJ11 mutation, <a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a> identified a 215A-G transition in the ABCC8 gene, resulting in an asn72-to-ser (N72S) substitution, in combination with mosaic segmental paternal isodisomy for 11pter to 11p14. This region includes the ABCC8 gene, and thus uniparental disomy had unmasked a recessively acting mutation. The father was heterozygous for the mutation but did not have diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, GLU382LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356651;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=rs80356651" 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=rs80356651" 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=RCV000009678 OR RCV001089460" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009678, RCV001089460" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009678...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>), diagnosed before the age of 6 months, <a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a> identified a homozygous 1144G-A transition in the ABCC8 gene that resulted in a glu382-to-lys (E382K) substitution. The heterozygous, first-cousin parents were not diabetic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, ALA1185GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193929369 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193929369;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=rs193929369" 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=rs193929369" 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=RCV000009679 OR RCV001089461 OR RCV002243634 OR RCV002243635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009679, RCV001089461, RCV002243634, RCV002243635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009679...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>), diagnosed before the age of 6 months, the offspring of first cousins, <a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a> identified a homozygous mutation in the ABCC8 gene: a 3554C-A transversion resulting in an ala1185-to-glu substitution (A1185E). Neither parent was diabetic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, 134C-T, PRO45LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606623 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606623;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=rs267606623" 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=rs267606623" 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=RCV000009680 OR RCV002512948" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009680, RCV002512948" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009680...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>), <a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a> observed compound heterozygosity for mutations in the ABCC8 gene. One allele carried a 134C-T transition resulting in a pro45-to-leu substitution (P45L); the other carried a 4201G-A transition resulting in a gly1401-to-arg substitution (G1401R; <a href="#0025">600509.0025</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, GLY1401ARG
|
|
</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> rs137852676 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852676;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/rs137852676?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=rs137852676" 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=rs137852676" 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=RCV000009657 OR RCV000029263 OR RCV001277179 OR RCV001390783 OR RCV003321485 OR RCV003466873 OR RCV005042088" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009657, RCV000029263, RCV001277179, RCV001390783, RCV003321485, RCV003466873, RCV005042088" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009657...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gly1401-to-arg (G1401R) mutation in the ABCC8 gene that was found in compound heterozygous state in a patient with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>) by <a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a>, see <a href="#0024">600509.0024</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, 257T-G, VAL86GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193929360 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193929360;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=rs193929360" 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=rs193929360" 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=RCV000009681 OR RCV001089462" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009681, RCV001089462" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009681...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with permanent neonatal diabetes mellitus (PNDM3; <a href="/entry/618857">618857</a>) diagnosed at the age of 5 months, <a href="#8" class="mim-tip-reference" title="Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M. <strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong> Am. J. Hum. Genet. 81: 375-382, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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/10.1086/519174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17668386">Ellard et al. (2007)</a> found heterozygosity for a mutation in the ABCC8 gene: a 257T-G transversion resulting in a val86-to-gly substitution (V86G). This was one of 8 patients with this disorder associated with a heterozygous de novo mutation in ABCC8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17668386" 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="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, EX13DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032666" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032666" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032666</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male proband with diazoxide-unresponsive hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>), who had undergone near-total pancreatectomy and in whom a heterozygous 1-bp duplication (512dupT; <a href="#0028">600509.0028</a>) had previously been detected by <a href="#3" class="mim-tip-reference" title="Banerjee, I., Skae, M., Flanagan, S. E., Rigby, L., Patel, L., Didi, M., Blair, J., Ehtisham, S., Ellard, S., Cosgrove, K. E. <strong>The contribution of rapid K(ATP) channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.</strong> Europ. J. Endocr. 164: 733-740, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21378087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21378087</a>] [<a href="https://doi.org/10.1530/EJE-10-1136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21378087">Banerjee et al. (2011)</a>, <a href="#10" class="mim-tip-reference" title="Flanagan, S. E., Damhuis, A., Bannerjee, I., Rokicki, D., Jefferies, C., Kapoor, R. R., Hussain, K., Ellard, S. <strong>Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.</strong> Pediat. Diabetes 13: 285-289, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21978130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21978130</a>] [<a href="https://doi.org/10.1111/j.1399-5448.2011.00821.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21978130">Flanagan et al. (2012)</a> used MPLA and found that the patient also carried a heterozygous deletion of exon 13 in the ABCC8 gene. His unaffected parents were each heterozygous for 1 of the mutations. <a href="#10" class="mim-tip-reference" title="Flanagan, S. E., Damhuis, A., Bannerjee, I., Rokicki, D., Jefferies, C., Kapoor, R. R., Hussain, K., Ellard, S. <strong>Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.</strong> Pediat. Diabetes 13: 285-289, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21978130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21978130</a>] [<a href="https://doi.org/10.1111/j.1399-5448.2011.00821.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21978130">Flanagan et al. (2012)</a> also identified heterozygosity for the ABCC8 exon 13 deletion in another male proband who had undergone near-total pancreatectomy, histologic examination of which revealed normal pancreatic tissue, consistent with a focal lesion. The deletion was inherited from his unaffected father; pancreatic tissue was not available for loss-of-heterozygosity studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21978130+21378087" 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="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, 1-BP DUP, 512T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1564980510 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564980510;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=rs1564980510" 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=rs1564980510" 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=RCV000032667 OR RCV002254153 OR RCV002254154" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032667, RCV002254153, RCV002254154" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032667...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp duplication in the ABCC8 gene (512dupT) that was found in a patient with diazoxide-unresponsive hyperinsulinemic hypoglycemia (HHF1; <a href="/entry/256450">256450</a>) by <a href="#3" class="mim-tip-reference" title="Banerjee, I., Skae, M., Flanagan, S. E., Rigby, L., Patel, L., Didi, M., Blair, J., Ehtisham, S., Ellard, S., Cosgrove, K. E. <strong>The contribution of rapid K(ATP) channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.</strong> Europ. J. Endocr. 164: 733-740, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21378087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21378087</a>] [<a href="https://doi.org/10.1530/EJE-10-1136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21378087">Banerjee et al. (2011)</a> and <a href="#10" class="mim-tip-reference" title="Flanagan, S. E., Damhuis, A., Bannerjee, I., Rokicki, D., Jefferies, C., Kapoor, R. R., Hussain, K., Ellard, S. <strong>Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.</strong> Pediat. Diabetes 13: 285-289, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21978130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21978130</a>] [<a href="https://doi.org/10.1111/j.1399-5448.2011.00821.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21978130">Flanagan et al. (2012)</a>, see <a href="#0027">600509.0027</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21978130+21378087" 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="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ABCC8, IVS8, A-G, -1013
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs980458021 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs980458021;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=rs980458021" 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=rs980458021" 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=RCV000032668 OR RCV001211946 OR RCV003466885 OR RCV005042102" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032668, RCV001211946, RCV003466885, RCV005042102" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032668...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In 5 probands with diazoxide-unresponsive hypoglycemia due to focal hyperinsulinism (HHF1; <a href="/entry/256450">256450</a>), <a href="#11" class="mim-tip-reference" title="Flanagan, S. E., Xie, W., Caswell, R., Damhuis, A., Vianey-Saban, C., Akcay, T., Darendeliler, F., Bas, F., Guven, A., Siklar, Z., Ocal, G., Berberoglu, M., and 9 others. <strong>Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.</strong> Am. J. Hum. Genet. 92: 131-136, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23273570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23273570</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23273570[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/10.1016/j.ajhg.2012.11.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23273570">Flanagan et al. (2013)</a> identified heterozygosity for a c.1333-1013A-G transition (c.1333-1013A-G, NM_000352.3) deep within intron 8 of the ABCC8 gene, creating a cryptic splice donor site that results in the inclusion of an out-of-frame 76-bp pseudoexon and premature termination. The mutation was inherited from the father in 4 of the patients; in the fifth patient, the mutation was not found in the mother but no DNA was available from the father. The variant was also identified in homozygosity in 1 patient with diffuse hyperinsulinism diagnosed on postmortem examination, and was present in heterozygosity in both parents. Chromosome 11 microsatellite analysis revealed a shared haplotype among the 6 patients, 4 of whom were from Ireland, suggesting that the variant represents a founder mutation in the Irish population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23273570" 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></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</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="Aguilar-Bryan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aguilar-Bryan, L., Nichols, C. G., Wechsler, S. W., Clement, J. P., IV, Boyd, A. E., III, Gonzalez, G., Herrera-Sosa, H., Nguy, K., Bryan, J., Nelson, D. A.
|
|
<strong>Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.</strong>
|
|
Science 268: 423-426, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.7716547" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Babenko2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P.
|
|
<strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong>
|
|
New Eng. J. Med. 355: 456-466, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa055068" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Banerjee2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Banerjee, I., Skae, M., Flanagan, S. E., Rigby, L., Patel, L., Didi, M., Blair, J., Ehtisham, S., Ellard, S., Cosgrove, K. E.
|
|
<strong>The contribution of rapid K(ATP) channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.</strong>
|
|
Europ. J. Endocr. 164: 733-740, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21378087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21378087</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21378087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1530/EJE-10-1136" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bellanne-Chantelot2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellanne-Chantelot, C., Saint-Martin, C., Ribeiro, M.-J., Vaury, C., Verkarre, V., Arnoux, J.-B., Valayannopoulos, V., Gobrecht, S., Sempoux, C., Rahier, J., Fournet, J.-C., Jaubert, F., Aigrain, Y., Nihoul-Fekete, C., de Lonlay, P.
|
|
<strong>ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.</strong>
|
|
J. Med. Genet. 47: 752-759, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20685672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20685672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20685672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2009.075416" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="de Lonlay1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Lonlay, P., Fournet, J.-C., Rahier, J., Gross-Morand, M.-S., Poggi-Travert, F., Foussier, V., Bonnefont, J.-P., Brusset, M.-C., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C.
|
|
<strong>Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.</strong>
|
|
J. Clin. Invest. 100: 802-807, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259578</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259578" target="_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/JCI119594" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="de Wet2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Wet, H., Rees, M. G., Shimomura, K., Aittoniemi, J., Patch, A.-M., Flanagan, S. E., Ellard, S., Hattersley, A. T., Sansom, M. S. P., Ashcroft, F. M.
|
|
<strong>Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 18988-18992, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18025464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18025464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18025464[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=18025464" target="_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.0707428104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Dunne1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dunne, M. J., Kane, C., Shepherd, R. M., Sanchez, J. A., James, R. F. L., Johnson, P. R. V., Aynsley-Green, A., Lu, S., Clement, J. P., IV, Lindley, K. J., Seino, S., Aguilar-Bryan, L.
|
|
<strong>Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor.</strong>
|
|
New Eng. J. Med. 336: 703-706, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9041101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9041101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9041101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199703063361005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Ellard2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M.
|
|
<strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong>
|
|
Am. J. Hum. Genet. 81: 375-382, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17668386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17668386</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17668386[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=17668386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/519174" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Fantes1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fantes, J. A., Oghene, K., Boyle, S., Danes, S., Fletcher, J. M., Bruford, E. A., Williamson, K., Seawright, A., Schedl, A., Hanson, I., Zehetner, G., Bhogal, R., Lehrach, H., Gregory, S., Williams, J., Little, P. F. R., Sellar, G. C., Hoovers, J., Mannens, M., Weissenbach, J., Junien, C., van Heyningen, V., Bickmore, W. A.
|
|
<strong>A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.</strong>
|
|
Genomics 25: 447-461, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789978" target="_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(95)80045-n" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Flanagan2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Flanagan, S. E., Damhuis, A., Bannerjee, I., Rokicki, D., Jefferies, C., Kapoor, R. R., Hussain, K., Ellard, S.
|
|
<strong>Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.</strong>
|
|
Pediat. Diabetes 13: 285-289, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21978130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21978130</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21978130" target="_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.1399-5448.2011.00821.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Flanagan2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Flanagan, S. E., Xie, W., Caswell, R., Damhuis, A., Vianey-Saban, C., Akcay, T., Darendeliler, F., Bas, F., Guven, A., Siklar, Z., Ocal, G., Berberoglu, M., and 9 others.
|
|
<strong>Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.</strong>
|
|
Am. J. Hum. Genet. 92: 131-136, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23273570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23273570</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23273570[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=23273570" target="_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.ajhg.2012.11.017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Giurgea2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giurgea, I., Sempoux, C., Bellanne-Chantelot, C., Ribeiro, M., Hubert, L., Boddaert, N., Saudubray, J.-M., Robert, J.-J., Brunelle, F., Rahier, J., Jaubert, F., Nihoul-Fekete, C., de Lonlay, P.
|
|
<strong>The Knudson's two-hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism.</strong>
|
|
J. Clin. Endocr. Metab. 91: 4118-4123, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16882742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16882742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16882742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2006-0397" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Glaser1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Glaser, B., Chiu, K. C., Anker, R., Nestorowicz, A., Landau, H., Ben-Bassat, H., Shlomai, Z., Kaiser, N., Thornton, P. S., Stanley, C. A., Spielman, R. S., Gogolin-Ewens, K., Cerasi, E., Baker, L., Rice, J., Donis-Keller, H., Permutt, M. A.
|
|
<strong>Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene.</strong>
|
|
Nature Genet. 7: 185-188, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7920639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7920639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7920639" target="_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/ng0694-185" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Glaser1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Glaser, B., Furth, J., Stanley, C. A., Baker, L., Thornton, P. S., Landau, H., Permutt, M. A.
|
|
<strong>Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.</strong>
|
|
Hum. Mutat. 14: 23-29, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447255</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10447255" target="_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(1999)14:1<23::AID-HUMU3>3.0.CO;2-#" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Glaser1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Glaser, B., Ryan, F., Donath, M., Landau, H., Stanley, C. A., Baker, L., Barton, D. E., Thornton, P. S.
|
|
<strong>Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene.</strong>
|
|
Diabetes 48: 1652-1657, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10426386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10426386</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10426386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diabetes.48.8.1652" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Goksel1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goksel, D. L., Fischbach, K., Duggirala, R., Mitchell, B. D., Aguilar-Bryan, L., Blangero, J., Stern, M. P., O'Connell, P.
|
|
<strong>Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.</strong>
|
|
Hum. Genet. 103: 280-285, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9799081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9799081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9799081" target="_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/s004390050817" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Gribble1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gribble, F. M., Tucker, S. J., Ashcroft, F. M.
|
|
<strong>The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.</strong>
|
|
EMBO J. 16: 1145-1152, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9135131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9135131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9135131" target="_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/emboj/16.6.1145" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Henwood2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Henwood, M. J., Kelly, A., MacMullen, C., Bhatia, P., Ganguly, A., Thornton, P. S., Stanley, C. A.
|
|
<strong>Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.</strong>
|
|
J. Clin. Endocr. Metab. 90: 789-794, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15562009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15562009</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15562009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-1604" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Huopio2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huopio, H., Otonkoski, T., Vauhkonen, I., Reimann, F., Ashcroft, F. M., Laakso, M.
|
|
<strong>A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. (Commentary)</strong>
|
|
Lancet 361: 301-307, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12559865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12559865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12559865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/S0140-6736(03)12325-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Huopio2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huopio, H., Reimann, F., Ashfield, R., Komulainen, J., Lenko, H.-L., Rahier, J., Vauhkonen, I., Kere, J., Laakso, M., Ashcroft, F., Otonkoski, T.
|
|
<strong>Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.</strong>
|
|
J. Clin. Invest. 106: 897-906, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11018078[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=11018078" target="_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/JCI9804" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Inagaki1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Inagaki, N., Gonoi, T., Clement, J. P., IV., Namba, N., Inazawa, J., Gonzalez, G., Aguilar-Bryan, L., Seino, S., Bryan, J.
|
|
<strong>Reconstitution of I(KATP): an inward rectifier subunit plus the sulfonylurea receptor.</strong>
|
|
Science 270: 1166-1169, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7502040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7502040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7502040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.270.5239.1166" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Inoue1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Inoue, H., Ferrer, J., Welling, C. M., Elbein, S. C., Hoffman, M., Mayorga, R., Warren-Perry, M., Zhang, Y., Millns, H., Turner, R., Province, M., Bryan, J., Permutt, M. A., Aguilar-Bryan, L.
|
|
<strong>Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.</strong>
|
|
Diabetes 45: 825-831, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8635661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8635661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8635661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diab.45.6.825" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Laukkanen2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laukkanen, O., Pihlajamaki, J., Lindstrom, J., Eriksson, J., Valle, T. T., Hamalainen, H., Ilanne-Patrikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J., Uusitupa, M., Laakso, M., Finnish Diabetes Prevention Study Group.
|
|
<strong>Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.</strong>
|
|
J. Clin. Endocr. Metab. 89: 6286-6290, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15579791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15579791</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15579791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-1204" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Lohmueller2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., Hirschhorn, J. N.
|
|
<strong>Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease.</strong>
|
|
Nature Genet. 33: 177-182, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12524541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12524541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12524541" target="_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/ng1071" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Magge2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Magge, S. N., Shyng, S.-L., MacMullen, C., Steinkrauss, L., Ganguly, A., Katz, L. E. L., Stanley, C. A.
|
|
<strong>Familial leucine-sensitive hypoglycemia in infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.</strong>
|
|
J. Clin. Endocr. Metab. 89: 4450-4456, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15356046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15356046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15356046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-0441" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Matsuo2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsuo, M., Trapp, S., Tanizawa, Y., Kioka, N., Amachi, T., Oka, Y., Ashcroft, F. M., Ueda, K.
|
|
<strong>Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
J. Biol. Chem. 275: 41184-41191, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10993895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10993895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10993895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M006503200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Meirhaeghe2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meirhaeghe, A., Helbecque, N., Cottel, D., Arveiler, D., Ruidavets, J.-B., Haas, B., Ferrieres, J., Tauber, J.-P., Bingham, A., Amouyel, P.
|
|
<strong>Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study.</strong>
|
|
Am. J. Med. Genet. 101: 4-8, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1297" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Nestorowicz1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nestorowicz, A., Glaser, B., Wilson, B. A., Shyng, S.-L., Nichols, C. G., Stanley, C. A., Thornton, P. S., Permutt, M. A.
|
|
<strong>Genetic heterogeneity in familial hyperinsulinism.</strong>
|
|
Hum. Molec. Genet. 7: 1119-1128, 1998. Note: Erratum: Hum. Molec. Genet. 7: 1527 only, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618169</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618169" target="_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/7.7.1119" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Nestorowicz1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A.
|
|
<strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong>
|
|
Hum. Molec. Genet. 5: 1813-1822, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.11.1813" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Otonkoski1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otonkoski, T., Ammala, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K., Ashfield, R., Huang, E., Komulainen, J., Ashcroft, F. M., Dunne, M. J., Kere, J., Thomas, P. M.
|
|
<strong>A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.</strong>
|
|
Diabetes 48: 408-415, and 415, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10334322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10334322</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10334322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diabetes.48.2.408" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Philipson1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Philipson, L. H., Steiner, D. F.
|
|
<strong>Pas de deux or more: the sulfonylurea receptor and K+ channels.</strong>
|
|
Science 268: 372-373, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716539</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.7716539" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Pinney2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A.
|
|
<strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong>
|
|
J. Clin. Invest. 118: 2877-2886, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18596924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18596924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18596924[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=18596924" target="_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/JCI35414" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Pocai2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., Rossetti, L.
|
|
<strong>Hypothalamic K(ATP) channels control hepatic glucose production.</strong>
|
|
Nature 434: 1026-1031, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846348</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15846348" target="_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/nature03439" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Proks2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Proks, P., Arnold, A. L., Bruining, J., Girard, C., Flanagan, S. E., Larkin, B., Colclough, K., Hattersley, A. T., Ashcroft, F. M., Ellard, S.
|
|
<strong>A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.</strong>
|
|
Hum. Molec. Genet. 15: 1793-1800, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16613899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16613899</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16613899" target="_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/ddl101" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Reis2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reis, A. F., Ye, W.-Z., Dubois-Laforgue, D., Bellanne-Chantelot, C., Timsit, J., Velho, G.
|
|
<strong>Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians.</strong>
|
|
Hum. Genet. 107: 138-144, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030411" target="_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/s004390000345" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Ryan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ryan, F., Devaney, D., Joyce, C., Nestorowicz, A., Permutt, M. A., Glaser, B., Barton, D. E., Thornton, P. S.
|
|
<strong>Hyperinsulinism: molecular aetiology of focal disease.</strong>
|
|
Arch. Dis. Child 79: 445-447, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10193261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10193261</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10193261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/adc.79.5.445" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Simard2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Simard, J. M., Chen, M., Tarasov, K. V., Bhatta, S., Ivanova, S., Melnitchenko, L., Tsymbalyuk, N., West, G. A., Gerzanich, V.
|
|
<strong>Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.</strong>
|
|
Nature Med. 12: 433-440, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16550187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16550187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16550187[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=16550187" target="_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/nm1390" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Thomas1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomas, P. M., Cote, G. J., Hallman, D. M., Mathew, P. M.
|
|
<strong>Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
Am. J. Hum. Genet. 56: 416-421, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7847376" 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="39" class="mim-anchor"></a>
|
|
<a id="Thomas1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J.
|
|
<strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
Science 268: 426-429, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7716548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7716548</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7716548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.7716548" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Thomas1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J.
|
|
<strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
Am. J. Hum. Genet. 59: 510-518, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8751851" 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="41" class="mim-anchor"></a>
|
|
<a id="Thornton2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thornton, P. S., MacMullen, C., Ganguly, A., Ruchelli, E., Steinkrauss, L., Crane, A., Aguilar-Bryan, L., Stanley, C. A.
|
|
<strong>Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.</strong>
|
|
Diabetes 52: 2403-2410, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12941782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12941782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12941782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diabetes.52.9.2403" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Thornton1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thornton, P. S., Satin-Smith, M. S., Herold, K., Glaser, B., Chiu, K. C., Nestorowicz, A., Permutt, M. A., Baker, L., Stanley, C. A.
|
|
<strong>Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.</strong>
|
|
J. Pediat. 132: 9-14, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9469993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9469993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9469993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0022-3476(98)70477-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Tornovsky2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tornovsky, S., Crane, A., Cosgrove, K. E., Hussain, K., Lavie, J., Heyman, M., Nesher, Y., Kuchinski, N., Ben-Shushan, E., Shatz, O., Nahari, E., Potikha, T., and 11 others.
|
|
<strong>Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.</strong>
|
|
J. Clin. Endocr. Metab. 89: 6224-6234, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15579781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15579781</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15579781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2004-1233" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Verkarre1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verkarre, V., Fournet, J.-C., de Lonlay, P., Gross-Morand, M.-S., Devillers, M., Rahier, J., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C.
|
|
<strong>Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.</strong>
|
|
J. Clin. Invest. 102: 1286-1291, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9769320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9769320</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9769320" target="_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/JCI4495" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 06/13/2018
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 2/4/2013<br>Marla J. F. O'Neill - updated : 3/20/2009<br>Marla J. F. O'Neill - updated : 5/16/2008<br>Victor A. McKusick - updated : 7/26/2007<br>John A. Phillips, III - updated : 7/13/2007<br>John A. Phillips, III - updated : 8/22/2006<br>Marla J. F. O'Neill - updated : 8/11/2006<br>Cassandra L. Kniffin - updated : 5/15/2006<br>Marla J. F. O'Neill - updated : 3/22/2006<br>Marla J. F. O'Neill - updated : 3/21/2006<br>Marla J. F. O'Neill - updated : 3/16/2006<br>Ada Hamosh - updated : 5/3/2005<br>John A. Phillips, III - updated : 4/21/2005<br>Anne M. Stumpf - reorganized : 4/21/2005<br>Victor A. McKusick - updated : 3/10/2003<br>Victor A. McKusick - updated : 1/30/2003<br>Victor A. McKusick - updated : 5/16/2001<br>Paul J. Converse - updated : 3/27/2001<br>John A. Phillips, III - updated : 11/8/2000<br>Victor A. McKusick - updated : 9/14/2000<br>Victor A. McKusick - updated : 8/16/1999<br>Ada Hamosh - updated : 3/18/1999<br>Victor A. McKusick - updated : 10/16/1998<br>Victor A. McKusick - updated : 7/8/1998<br>Victor A. McKusick - updated : 2/27/1998<br>Victor A. McKusick - updated : 4/11/1997<br>Moyra Smith - updated : 1/31/1997<br>Perseveranda M. Cagas - updated : 9/23/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 4/28/1995
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 02/25/2025
|
|
</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 : 02/25/2025<br>carol : 02/25/2025<br>alopez : 02/24/2025<br>alopez : 12/01/2020<br>carol : 05/04/2020<br>alopez : 04/30/2020<br>alopez : 04/30/2020<br>alopez : 04/30/2020<br>carol : 03/05/2019<br>alopez : 06/13/2018<br>carol : 12/20/2017<br>carol : 07/21/2017<br>carol : 09/12/2016<br>joanna : 07/01/2016<br>mcolton : 6/11/2015<br>carol : 3/10/2015<br>alopez : 9/4/2014<br>carol : 2/4/2013<br>terry : 7/6/2012<br>wwang : 3/30/2009<br>terry : 3/20/2009<br>carol : 5/16/2008<br>alopez : 7/30/2007<br>terry : 7/26/2007<br>alopez : 7/13/2007<br>alopez : 11/21/2006<br>alopez : 11/21/2006<br>carol : 9/5/2006<br>joanna : 8/31/2006<br>alopez : 8/22/2006<br>wwang : 8/16/2006<br>terry : 8/11/2006<br>wwang : 5/24/2006<br>ckniffin : 5/15/2006<br>carol : 3/23/2006<br>carol : 3/22/2006<br>carol : 3/21/2006<br>carol : 3/20/2006<br>carol : 3/16/2006<br>carol : 3/16/2006<br>joanna : 11/4/2005<br>alopez : 5/10/2005<br>terry : 5/3/2005<br>alopez : 4/21/2005<br>alopez : 4/21/2005<br>alopez : 4/21/2005<br>terry : 5/15/2003<br>tkritzer : 5/7/2003<br>carol : 3/17/2003<br>carol : 3/17/2003<br>tkritzer : 3/13/2003<br>terry : 3/10/2003<br>alopez : 1/31/2003<br>terry : 1/30/2003<br>mcapotos : 5/23/2001<br>mcapotos : 5/22/2001<br>terry : 5/16/2001<br>mgross : 3/27/2001<br>alopez : 3/22/2001<br>terry : 11/8/2000<br>carol : 10/17/2000<br>mcapotos : 10/5/2000<br>mcapotos : 9/26/2000<br>terry : 9/14/2000<br>carol : 11/10/1999<br>carol : 11/9/1999<br>jlewis : 8/24/1999<br>terry : 8/16/1999<br>terry : 8/16/1999<br>jlewis : 8/16/1999<br>alopez : 3/18/1999<br>alopez : 3/18/1999<br>carol : 10/28/1998<br>terry : 10/16/1998<br>carol : 7/13/1998<br>terry : 7/8/1998<br>terry : 6/4/1998<br>carol : 3/28/1998<br>alopez : 2/27/1998<br>terry : 2/27/1998<br>mark : 4/11/1997<br>mark : 4/11/1997<br>alopez : 4/2/1997<br>terry : 4/1/1997<br>mark : 1/31/1997<br>terry : 1/31/1997<br>mark : 1/30/1997<br>terry : 11/14/1996<br>terry : 9/25/1996<br>mark : 9/23/1996<br>mark : 11/16/1995<br>mimadm : 11/3/1995<br>terry : 6/26/1995<br>terry : 5/3/1995<br>mark : 4/28/1995
|
|
</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> 600509
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 8; ABCC8
|
|
|
|
</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">
|
|
SULFONYLUREA RECEPTOR; SUR<br />
|
|
SUR1<br />
|
|
SULFONYLUREA RECEPTOR, BETA CELL HIGH AFFINITY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: ABCC8</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 44054006, 609580007, 62151007;
|
|
|
|
|
|
<strong>ICD10CM:</strong> E11;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 11p15.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:17,392,498-17,476,845 </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="5">
|
|
<span class="mim-font">
|
|
11p15.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, noninsulin-dependent
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
125853
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, permanent neonatal 3, with or without neurologic features
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
618857
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, transient neonatal 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610374
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hyperinsulinemic hypoglycemia, familial, 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
256450
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypoglycemia of infancy, leucine-sensitive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
240800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</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>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sulfonylureas are a class of drugs widely used as oral hypoglycemics to promote insulin secretion in the treatment of type 2 diabetes mellitus (T2D, NIDDM; see 125853). These drugs interact with the sulfonylurea receptor of pancreatic beta cells and inhibit the conductance of adenosine triphosphate (ATP)-dependent potassium channels. Aguilar-Bryan et al. (1995) cloned the cDNA for the high-affinity sulfonylurea receptor. Analysis of the predicted amino acid sequence indicated that the gene is a member of the ATP-binding cassette or traffic ATPase superfamily with multiple membrane-spanning domains and 2 nucleotide-binding folds. The results suggested that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect K(ATP) channel activity, and thereby modulate insulin release. Biochemical studies by Aguilar-Bryan et al. (1995) indicated that SUR is a large membrane protein (140 to 170 kD). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By fluorescence in situ hybridization, Thomas et al. (1995) showed that the SUR gene maps to 11p15.1. Inagaki et al. (1995) determined that the BIR (600937) and SUR genes are clustered at 11p15.1, with the BIR gene immediately 3-prime of the SUR gene. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Inagaki et al. (1995) coexpressed SUR with BIR and observed reconstitution of an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to ATP, inhibited by sulfonylureas, and activated by diazoxide. The authors concluded that these pancreatic beta-cell potassium channels are a complex composed of at least 2 subunits: BIR and SUR. </p><p>Philipson and Steiner (1995) discussed the significance of the work on SUR. They compared the SUR protein with other members of the family of ATP-binding cassette proteins, including the multidrug resistance (MDR) proteins (e.g., 171050), which cause chemotherapeutic drug resistance when overexpressed, and the CFTR protein (602421), which is mutant in patients with cystic fibrosis (219700). </p><p>To test the effect of abolition of ATP hydrolysis on K-ATP channel activation by Mg-ADP and diazoxide in Xenopus oocytes, Gribble et al. (1997) mutated the critical lysine residues of the Walker A motifs in the first (K719A) and second (K1384M) nucleotide-binding domains (NBDs) of SUR1. The Walker A lysine of NBD1, but not of NBD2, was essential for activation. Both Walker A lysines were essential for potentiation by Mg-ADP. Mutant currents were more sensitive to inhibition by ATP than were wildtype currents. Metabolic inhibition led to activation of wildtype and K1384M currents, but not K719A or K719A/K1384M currents. These results suggested to the authors that an additional factor, besides ATP and ADP, regulates K-ATP channel activity. </p><p>Pocai et al. (2005) demonstrated that activation of K-ATP channels in the mediobasal hypothalamus is sufficient to lower blood glucose levels through inhibition of hepatic gluconeogenesis. The infusion of a K-ATP blocker within the mediobasal hypothalamus, or the surgical resection of the hepatic branch of the vagus nerve, negated the effects of central insulin (176730) and halved the effects of systemic insulin on hepatic glucose production in the mouse. Consistent with these results, mice lacking the SUR1 subunit of the K-ATP channel were resistant to the inhibitory action of insulin on gluconeogenesis. Pocai et al. (2005) concluded that activation of hypothalamic K-ATP channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycemia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Familial Hyperinsulinemic Hypoglycemia 1</em></strong></p><p>
|
|
Familial hyperinsulinemic hypoglycemia (see HHF1, 256450), a disorder characterized by unregulated insulin secretion, was mapped to 11p15.1-p14 by linkage analysis (Glaser et al., 1994; Thomas et al., 1995; Fantes et al., 1995). The SUR protein was thought to be a likely candidate since it is a putative subunit of the beta-cell ATP-sensitive potassium channel, K(ATP), a modulator of insulin secretion. Thomas et al. (1995) detected 2 separate SUR gene splice site mutations that segregated with the disease phenotype in affected individuals from 9 different families (600509.0001 and 600509.0002). Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide-binding domain (NBF2) of the SUR protein. </p><p>In further studies on the role of the SUR nucleotide-binding folds in hyperinsulinemic hypoglycemia, Thomas et al. (1996) demonstrated that disruption of the first nucleotide-binding fold (NBF1) likewise leads to HHF (600509.0003-600509.0005). The data indicated that both nucleotide-binding-fold regions of the sulfonylurea receptor are required for normal regulation of beta-cell ATP-dependent potassium channel activity and insulin secretion. </p><p>Nestorowicz et al. (1996) screened a proband from each of 25 Ashkenazi Jewish families with hyperinsulinemic hypoglycemia for mutations in the SUR gene by SSCP analysis of genomic DNA and subsequent sequence analysis. They identified 2 common mutations. One mutation was a novel in-frame deletion of the codon for F1388 (600509.0006). This mutation creates a unique BseR1 restriction site in exon 34 allowing detection of noncarriers, homozygotes, and heterozygotes. The second mutation was a previously described G-to-A transition at position -9 of the 3-prime splice site of intron 32 (600509.0002). Extended haplotype analysis in the D11S1901-D11S1310 region revealed that these 2 mutations were associated with an H1 haplotype in 88% of patients studied, suggesting a founder effect. Nestorowicz et al. (1996) determined that F1388-deleted SUR is unable to form a functional K(ATP) channel with Kir6.2. </p><p>Nestorowicz et al. (1998) screened 45 familial hyperinsulinism probands of various ethnic origins for mutations in the SUR gene. SSCP and nucleotide sequence analyses of genomic DNA revealed a total of 17 novel and 3 previously described mutations. The novel mutations comprised 1 nonsense and 10 missense mutations, 2 deletions, 3 mutations in consensus splice site sequences, and an in-frame insertion of 6 nucleotides. One mutation occurred in the first nucleotide-binding domain (NBF1) of the SUR molecule and another 8 mutations were located in the second nucleotide-binding domain (NBF2), including 2 at highly conserved amino acid residues within the Walker A sequence motif. Most of the other mutations were distributed throughout the 3 putative transmembrane domains of the SUR protein. With the exception of the 3993-9G-A mutation (600509.0002), which was detected on 4.5% (4 of 88) disease chromosomes, allelic frequencies for the identified mutations varied between 1.1% and 2.3%. The clinical manifestations of familial hyperinsulinism in those patients homozygous for mutations in the SUR gene were described. In contrast to the allelic homogeneity of familial hyperinsulinism found in Ashkenazi Jewish patients (Nestorowicz et al., 1996), the findings of the wider study suggested that a large degree of allelic heterogeneity at the SUR locus exists in non-Ashkenazi patients. </p><p>From a morphologic standpoint, there are 2 types of histopathologic lesions underlying PHHI: a focal adenomatous hyperplasia of islet cells of the pancreas in approximately 30% of sporadic cases, and a diffuse form. In sporadic focal forms, specific losses of maternal alleles (LOH) of the imprinted chromosomal region 11p15, restricted to the hyperplastic area of the pancreas, were detected by de Lonlay et al. (1997). Similar mechanisms are observed in embryonal tumors and in the Beckwith-Wiedemann syndrome (BWS; 130650); the latter condition is also associated with neonatal but transient hyperinsulinism. The same chromosomal region, 11p15.1, includes the SUR gene and the KCNJ11 gene (600937), which code for the 2 subunits of the beta-cell K(+)-ATP channel. Recessive mutations in these genes cause recessive familial forms of PHHI, but appear not to be imprinted. Although the parental bias in loss of maternal alleles did not argue in favor of direct involvement of the SUR or KCNJ11 genes, the LOH may unmask a recessive mutation leading to persistent hyperinsulinism. Verkarre et al. (1998) reported somatic reduction to hemizygosity or homozygosity of a paternal SUR constitutional heterozygous mutation in 4 patients with a focal form of PHHI. Thus, this somatic event, which leads to both beta cell proliferation and hyperinsulinism, can be considered as the somatic equivalent, restricted to a microscopic focal lesion, of constitutional uniparental disomy associated with unmasking of a heterozygous paternal mutation leading to a somatic recessive disorder. </p><p>Ryan et al. (1998) reported a similar situation in a non-Jewish hyperinsulinism patient with a single, paternally inherited SUR1 mutation. Glaser et al. (1999) proposed that some or all of the subjects with paternally inherited SUR1 mutations may have focal disease. In the 2 patients who underwent surgery, focal adenomatosis was documented. In one of these patients, tissue was available and reduction to homozygosity for the SUR1 mutation was also documented. </p><p>Glaser et al. (1999) examined pancreatic tissue from 3 patients with single paternal-allele mutations of the SUR1 gene and found focal beta-cell hyperplasia. DNA extracted from the focal lesions and adjacent normal pancreas revealed loss of the maternal chromosome 11p15, resulting in reduction to homozygosity for the SUR1 mutation, within the focal lesions only. Glaser et al. (1999) suggested that the combination of a paternally inherited SUR1 mutation along with somatic loss of the maternal allele of chromosome 11p may be the genetic etiology of most, if not all, cases of focal hyperinsulinism. </p><p>In 15 of 24 Finnish patients with hyperinsulinemic hypoglycemia, Otonkoski et al. (1999) identified homozygosity or heterozygosity for a V187D mutation in the ABCC8 gene (600509.0013). The mutation was not found in 23 patients with hyperinsulinemic hypoglycemia from outside Finland, suggestive of a founder effect. In vitro studies demonstrated that the presence of the V187D mutation renders the potassium channel completely nonfunctional. Parents and sibs who were carriers of the mutation were apparently asymptomatic; Otonkoski et al. (1999) postulated the presence of another mutation in heterozygous affected individuals. </p><p>In 5 affected members of the 3-generation family ('family 1') with hyperinsulinemic hypoglycemia originally reported by Thornton et al. (1998), Thornton et al. (2003) identified heterozygosity for a 3-bp deletion in exon 34 of the ABCC8 gene (600509.0014). </p><p>In an infant of Spanish descent with hyperinsulinemic hypoglycemia, Tornovsky et al. (2004) identified a mutation in the promoter of the ABCC8 gene (600509.0015) on the paternal allele. No mutation was found on the maternal allele. No focal lesion had been identified after near-total pancreatectomy, but the specimen was not available for reevaluation. </p><p>Henwood et al. (2005) measured acute insulin responses (AIRs) to calcium, leucine, glucose, and tolbutamide in 22 infants with recessive ABCC8 or KCNJ11 mutations, 8 of whom had diffuse hyperinsulinism and 14 of whom had focal hyperinsulinism. Of the 24 total mutations, 7 showed evidence of residual K(ATP) channel function: 2 of the patients with partial defects were homozygous and 4 heterozygous for amino acid substitutions or insertions, and 1 was a compound heterozygote for 2 premature stop codons. </p><p>Giurgea et al. (2006) reported 3 patients with hyperinsulinemic hypoglycemia, all with paternally inherited SUR1 mutations. The first 2 patients both had 2 distinct foci of islet cell hyperplasia, and the third patient had a very large area of islet cell hyperplasia involving the major portion of the pancreas. In patients 1 and 2, haploinsufficiency for the maternal 11p15.5 region resulted from a somatic deletion specific for each of the focal lesions, as shown by the diversity of deletion breakpoints. In patient 3, an identical somatic maternal 11p15 deletion demonstrated by similar breakpoints was shown in 2 independent lesion samples, suggesting a very early event during pancreas embryogenesis. Giurgea et al. (2006) concluded that individual patients with focal hyperinsulinism may have more than 1 focal pancreatic lesion due to separate somatic maternal deletion of the 11p15 region. These patients and those with solitary focal lesions may follow the 2-hit model described by Knudson. </p><p>Pinney et al. (2008) identified 14 different dominantly inherited K(ATP) channel mutations in 16 unrelated families, 13 with mutations in the ABCC8 gene (see, e.g., 600509.0011) and 3 with mutations in the KCNJ11 gene (see, e.g., 600937.0020). Unlike recessive mutations, dominantly inherited K(ATP) mutant subunits trafficked normally to the plasma membrane when expressed in simian kidney cells; dominant mutations also resulted in different channel-gating defects, with dominant ABCC8 mutations diminishing channel responses to magnesium adenosine diphosphate or diazoxide and dominant KCNJ11 mutations impairing channel opening even in the absence of nucleotides. Pinney et al. (2008) concluded that there are distinctive features of dominant K(ATP) hyperinsulinism compared to the more common and more severe recessive form, including retention of normal subunit trafficking, impaired channel activity, and a milder hypoglycemia phenotype that may escape detection in infancy and is often responsive to diazoxide medical therapy. </p><p>Bellanne-Chantelot et al. (2010) analyzed the ABCC8 and KCNJ11 genes in 109 diazoxide-unresponsive patients with congenital hyperinsulinism and identified mutations in 89 (82%) of the probands. A total of 118 mutations were found, including 106 (90%) in ABCC8 and 12 (10%) in KCNJ11; 94 of the 118 were different mutations, and 41 had been previously reported. The 37 patients diagnosed with focal disease all had heterozygous mutations, whereas 30 (47%) of 64 patients known or suspected to have diffuse disease had homozygous or compound heterozygous mutations, 22 (34%) had a heterozygous mutation, and 12 (19%) had no mutation in the ABCC8 or KCNJ11 genes. The authors concluded that ABCC8 gene defects are the most important cause of diazoxide-unresponsive congenital hyperinsulinism. </p><p>In 29 patients with diazoxide-unresponsive hyperinsulinemic hypoglycemia, in whom direct sequencing revealed no mutation in the ABCC8 or KCNJ11 genes, or in whom a single recessively acting heterozygous ABCC8 mutation had been identified despite histologically confirmed diffuse pancreatic disease, Flanagan et al. (2012) used multiplex ligation-dependent probe amplification (MPLA) for ABCC8 dosage analysis and identified 3 different partial gene deletions (see, e.g., 600509.0027) in 4 patients (14%). Two of the patients, who had diffuse disease, also carried another ABCC8 mutation that had previously been detected by sequence analysis (see, e.g., 600509.0028), whereas the 2 patients with focal disease carried only the deletion in ABCC8. Pancreatic tissue was not available from the latter 2 patients for loss-of-heterozygosity studies. </p><p>In 5 patients with diazoxide-unresponsive focal hyperinsulinism in whom direct sequencing and MPLA dosage analysis failed to reveal a mutation in the ABCC8 or KCNJ11 genes, Flanagan et al. (2013) performed next-generation sequencing of the entire genomic region of ABCC8 and identified heterozygosity for a paternally inherited deep intronic splicing variant (c.1333-1013A-G; 600509.0029). The variant was also identified in homozygosity in 1 patient with diffuse hyperinsulinism. Chromosome 11 microsatellite analysis revealed a shared haplotype among the 6 patients, 4 of whom were from Ireland, suggesting that the variant represents a founder mutation in the Irish population. </p><p><strong><em>Type 2 Diabetes Mellitus</em></strong></p><p>
|
|
Goksel et al. (1998) found that a silent single-nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-AGA; arg1273 to arg) was strongly associated with insulin response to an oral glucose load in nondiabetic Mexican-American subjects. This observation prompted Reis et al. (2000) to investigate the possible association of this SNP with type 2 diabetes (T2D; see 125853) in French Caucasian subjects. They observed an increased frequency of the A allele in patients compared with controls. This association was stronger in the subgroup of patients who were diagnosed at age 45 years or younger. Unexpectedly, the G allele was strongly associated with arterial hypertension in obese diabetic subjects. </p><p>Laukkanen et al. (2004) investigated whether common polymorphisms in the ABCC8 and KCNJ11 genes were associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. The 1273AGA allele of the ABCC8 gene was associated with a 2-fold risk of type 2 diabetes (odds ratio (OR), 2.00; 95% CI, 1.19-3.36; P = 0.009). This silent polymorphism was in linkage disequilibrium with 3 promoter polymorphisms, and they formed a high-risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09-3.27; P = 0.023). Subjects with both the high-risk haplotype of the ABCC8 gene and the 23K allele of the KCNJ11 gene (see E23K, 600937.0014) had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). Laukkanen et al. (2004) concluded that polymorphisms of the ABCC8 gene predict the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with that of the E23K polymorphism of the KCNJ11 gene. </p><p>Meirhaeghe et al. (2001) described an association study between type 2 diabetes and response to sulfonylurea therapy and a polymorphism of the SUR1 gene: IVS16-3T-C. They investigated 122 subjects in 3 French cities: Lille (in the north), Strasbourg (in the east), and Toulouse (in the south). The genotypes of 1,250 controls were in Hardy-Weinberg equilibrium as follows: TT 29%, TC 50%, and CC 21%. The frequency of the -3C allele was 0.46 in controls. In type 2 diabetes cases, the frequency of the C allele was 0.53. Subjects bearing at least one -3C allele and treated with sulfonylurea agents had fasting plasma triglyceride concentrations 35% lower than subjects who were TT homozygous, whereas no difference could be detected between genotypes in subjects with T2D treated with other medications. </p><p>Lohmueller et al. (2003) performed a metaanalysis of genetic association studies to evaluate the contribution of common variants with a susceptibility to common disease. They concluded that there are probably many common variants in the human genome with modest but real effects on common disease risk, and that studies using large samples will convincingly identify such variants. They analyzed 301 published studies covering 25 different reported associations. There was a large excess of studies replicating the first positive reports, inconsistent with the hypothesis of no true positive associations. This excess of replications could not be reasonably explained by publication bias and was concentrated among 11 of the 25 associations. The C/T SNP in exon 22 of the ABCC8 gene, which was first reported to show association of the T allele with type 2 diabetes (Inoue et al., 1996), was one of these. Another was association of a -3 T/C SNP in intron 24, with C showing association with type 2 diabetes, reported also by Inoue et al. (1996). </p><p><strong><em>Permanent Neonatal Diabetes Mellitus 3</em></strong></p><p>
|
|
In a 27-year-old man who had permanent neonatal diabetes (PNDM3; 618857) with severe developmental delay and generalized epileptiform activity on EEG, a triad referred to as DEND, Proks et al. (2006) identified heterozygosity for a de novo missense mutation (F132L; 600509.0016) in the ABCC8 gene. Functional studies showed that F132L markedly reduced the sensitivity of the K(ATP) channel to inhibition by MgATP, thereby increasing the whole-cell K(ATP) current; the authors noted that the functional consequence of the F132L mutation mirrors that of KCNJ11 mutations causing neonatal diabetes. </p><p>From a group of 73 patients with neonatal diabetes, Babenko et al. (2006) screened the ABCC8 gene in 34 who did not have alterations in chromosome 6q or mutations in the KCNJ11 or GCK (138079) genes. In 2 patients with permanent neonatal diabetes, they identified heterozygosity for a mutation (600509.0017 and 600509.0018, respectively). They also identified heterozygosity for 5 different mutations (see, e.g., 600509.0019-600509.0020) in 7 patients with transient neonatal diabetes (see 610374). Mutant channels in intact cells and in physiologic concentrations of magnesium ATP had markedly higher activity than did wildtype channels. These overactive channels remained sensitive to sulfonylurea, and treatment with sulfonylureas resulted in euglycemia. The mutation-positive fathers of 5 of the probands with transient neonatal diabetes developed type 2 diabetes mellitus (125853) in adulthood; Babenko et al. (2006) proposed that mutations of the ABCC8 gene may give rise to a monogenic form of type 2 diabetes with variable expression and age at onset. The authors noted that dominant mutations in ABCC8 accounted for 12% of cases of neonatal diabetes in the study group. </p><p>Ellard et al. (2007) studied a cohort of 59 patients with permanent neonatal diabetes who received a diagnosis before 6 months of age and who did not have a mutation in KCNJ11 (600937). ABCC8 gene mutations were identified in 16 of the 59 patients (see, e.g., 600509.0021-600509.0026), including 8 patients with heterozygous de novo mutations. The other 8 patients carried homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a rat model of ischemic stroke (601367), Simard et al. (2006) found upregulation of Sur1 expression in ischemic neurons, astrocytes, and capillaries. Upregulation of Sur1 was linked to activation of the transcription factor Sp1 (189906) and was associated with expression of functional nonselective cation channels, which they called the NC(Ca-ATP) channel, but not K(ATP) channels. Treatment with low-dose glibenclamide, which blocks Sur1 and the NC(Ca-ATP) channel, reduced cerebral edema, infarct volume, and mortality by 50%. Simard et al. (2006) concluded that the NC(Ca-ATP) channel is involved in the development of cerebral edema and that targeting Sur1 may provide a new therapeutic approach to stroke. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>29 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, IVS, G-A, -1, EXON CHI DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000009654, RCV001040039, RCV001260357, RCV001826455, RCV003466843
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a child with hyperinsulinemic hypoglycemia (HHF1; 256450), born of consanguineous parents, Thomas et al. (1995) showed that a cloned pancreatic cDNA product had a 109-bp deletion within the NBF2 region of SUR, which corresponded to skipping of exon chi. The deletion caused disruption of the NBF2 consensus sequence by generating a frameshift and ultimately a premature stop signal 24 codons past the deletion. In genomic DNA, a homozygous G-to-A point mutation was found in the 3-prime end of the skipped exon. The recognition site for the restriction endonuclease MspI was destroyed by this base change. Both affected children in the family were homozygous, whereas the parents and 2 unaffected sibs were heterozygous. Twelve other affected children from 6 families of Saudi Arabian origin and 1 family of German origin were homozygous for the G-to-A point mutation, as demonstrated by loss of the MspI recognition site. The G-to-A mutation involved the last nucleotide of the skipped exon. Thomas et al. (1995) cited other instances in which G-to-A point mutations at this position had been observed to result in skipping of the exon containing the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, IVS32, G-A, -9, EXON ALPHA DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs151344623,
|
|
|
|
|
|
gnomAD: rs151344623,
|
|
|
|
|
|
ClinVar: RCV000009656, RCV000144995, RCV000590487, RCV001267446, RCV001277185, RCV002467491, RCV003473069, RCV004532316, RCV005049326
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with hyperinsulinemic hypoglycemia (HHF1; 256450), born of consanguineous parents, Thomas et al. (1995) found a mutation in the 3-prime splice site sequence preceding the NBF2 region. The G-to-A mutation destroyed an NciI restriction endonuclease recognition site, and homozygous loss of this site cosegregated with disease phenotype within the family. The G-to-A transition occurred at the ninth nucleotide from the 3-prime end of the intron preceding exon alpha, the first NBF2 exon. In a construct containing the mutation, 3 cryptic 3-prime splice sites within exon alpha were used in place of the wildtype splicing site. </p><p>Nestorowicz et al. (1996) demonstrated that this mutation in the SUR1 gene and the F1388del mutation (600509.0006) account for approximately 88% of hyperinsulinism-associated chromosomes in Ashkenazi Jewish patients. Haplotype analysis with microsatellite markers flanking the gene revealed that the delF1388 mutation, reported only in Ashkenazi probands, occurred on 2 related extended haplotypes. By contrast, the second, more common mutation (3992-9G-A) was associated with 9 different intergenic haplotypes and was reported in non-Jewish hyperinsulinism patients as well. Glaser et al. (1999) evaluated disease-associated chromosomes from 41 Ashkenazi Jewish and 2 non-Jewish hyperinsulinism patients carrying the 3992-9G-A mutation by assessing haplotypes defined by 9 common single-nucleotide polymorphisms (SNPs), 6 in the SUR1 gene and 3 in the closely linked KIR6.2 gene. They found that all 54 chromosomes carrying this particular mutation in the Jewish patients appeared to have originated from 1 founder mutation, whereas the same mutation in chromosomes from non-Jewish patients originated independently. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, GLY716VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72559723,
|
|
|
|
|
|
gnomAD: rs72559723,
|
|
|
|
|
|
ClinVar: RCV000009655, RCV000077845
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with hyperinsulinemic hypoglycemia (HHF1; 256450), born of consanguineous Malaysian parents, Thomas et al. (1996) found that the 6 exons that compose the NBF2 region of SUR had wildtype sequence. The NBF1 region, which is encoded by 8 exons that span approximately 8.2 kb of genomic sequence, shows strong homology with the NBF2 region and the NBF regions of other superfamily members. In of the proband of this family, a homozygous G-to-T transversion was found in the second exon (106-bp exon) of the NBF1 region. The point mutation was predicted to substitute a valine for the second glycine residue, G716V, of the Walker A motif of the NBF1 region, thereby altering a site that is conserved among all members of the ATP-binding-cassette superfamily. The mutation resulted in the loss of a BbvI restriction site allowing demonstration that the affected child was homozygous for the mutation, the parents heterozygous, and an unaffected sib homozygous for the wildtype allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, IVS, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1564905676,
|
|
|
|
|
|
|
|
ClinVar: RCV000009658, RCV001328359, RCV002251422, RCV002251423
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with hyperinsulinemic hypoglycemia (HHF1; 256450), born of nonconsanguineous German parents, Thomas et al. (1996) identified compound heterozygosity for 2 mutations located in sequences predicted to affect RNA processing of the SUR transcript. The first mutation was a G-to-A transition located at the -1 residue, within the 3-prime splice site of the fifth exon (99-bp exon) of the NBF1 region. The transition destroyed a BstNI restriction site. A G-to-A mutation in the -1 invariant residue in the 3-prime splice site in other genes has been found to result in 100% skipping of the involved exon or in both exon skipping and cryptic 3-prime splice site activation. The second mutation was a branch point mutation (600509.0005) at nucleotide -20 of the 146-bp exon preceding the NBF1 encoding region. The presence of this point mutation disrupted an invariant A residue of the branch-point consensus. This A-to-G change resulted in the destruction of an engineered SpeI restriction endonuclease site. Restriction analysis demonstrated that the first mutant allele was of maternal origin and the second of paternal origin. An unaffected brother was homozygous for the wildtype alleles. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, BRANCH POINT, A-G, -20
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs931436550,
|
|
|
|
|
|
gnomAD: rs931436550,
|
|
|
|
|
|
ClinVar: RCV000009659, RCV001851768, RCV002266898, RCV002266899, RCV003460445, RCV004525849
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the branch point mutation in the ABCC8 gene that was found in compound heterozygous state in patients with hyperinsulinemic hypoglycemia (HHF1; 256450) by Thomas et al. (1996), see 600509.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, 3-BP DEL, PHE1388DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs151344624,
|
|
|
|
|
|
|
|
ClinVar: RCV000177757, RCV000201913, RCV000587070, RCV001277181, RCV002243861, RCV003462282, RCV004537448, RCV005042381
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Ashkenazi Jewish families with hyperinsulinemic hypoglycemia (HHF1; 256450), Nestorowicz et al. (1996) identified a 3-bp deletion in exon 34 of the SUR gene, resulting in deletion of phenylalanine-1388. The deletion was associated with a specific haplotype (H1) in the D11S1901-D11S1310 region. The mutation led to the generation of a novel BseR1 restriction site. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, EX35, G-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906407,
|
|
|
|
|
|
gnomAD: rs387906407,
|
|
|
|
|
|
ClinVar: RCV000009654, RCV001040039, RCV001260357, RCV001826455, RCV003466843
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Dunne et al. (1997) identified a G-to-A transition in the terminal nucleotide of exon 35 of the SUR gene in homozygous state in a child from consanguineous Saudi Arabian parents. The child and 2 sibs had persistent hyperinsulinemic hypoglycemia of infancy (HHF1; 256450). The 2 affected sibs had undergone partial pancreatectomy for the disorder. The proband was born at term after a normal gestation, weighed 4.25 kg, and had macrosomia and plethora, features of in utero hyperinsulinism. Two partial pancreatectomies were required for control of hypoglycemia. Histologic examination of the pancreas revealed diffuse nesidioblastosis. The parents were heterozygous for the G-A mutation. (The mutations previously discovered by Thomas et al. (1995, 1996) and by Nestorowicz et al. (1996) were not mentioned by Dunne et al. (1997).) </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ARG1353PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28936370,
|
|
|
|
|
|
gnomAD: rs28936370,
|
|
|
|
|
|
ClinVar: RCV000009662, RCV001851769, RCV002504772
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of persistent hyperinsulinemic hypoglycemia of infancy (HHF1; 256450) due to focal adenomatous hyperplasia, Verkarre et al. (1998) found a 4058G-C transversion in exon 33 of the paternally derived SUR gene, leading to an arg1353-to-pro (R1353P) amino acid substitution. The father was constitutionally heterozygous for the same mutation. This was 1 of 12 cases in which loss of maternal alleles of the 11p15 chromosomal region had been found, limited to the hyperplastic lesions of focal adenomatous hyperplasia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ARG1421CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28938469,
|
|
|
|
|
|
|
|
ClinVar: RCV000009663, RCV001235181, RCV001831557, RCV003473070, RCV005042018
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a sporadic case of persistent hyperinsulinemic hypoglycemia of infancy (HHF1; 256450) due to focal adenomatous hyperplasia, Verkarre et al. (1998) found a 4261C-T transition in exon 35 of the paternally-derived SUR gene, leading to an arg1421-to-cys (R1421C) amino acid substitution. The father was constitutionally heterozygous for the same mutation. This was 1 of 12 cases in which loss of maternal alleles of the 11p15 chromosomal region had been found, limited to the hyperplastic lesions of focal adenomatous hyperplasia. </p></div>
|
|
|
|
<p>Matsuo et al. (2000) analyzed the functional consequences of the R1421C mutation, which they referred to as R1420C. They showed that the mutation lowers the affinity of the nucleotide-binding fold 2 (NBF2) for ATP and ADP and abolishes the ability of nucleotide binding at NBF2 to stabilize 8-azido-ATP binding at NBF1. In addition, the mutation decreases the expression of potassium-ATP channels, and a smaller current in R1420C-PHHI beta cells leads to enhanced insulin secretion. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ARG1494TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28936371,
|
|
|
|
|
|
gnomAD: rs28936371,
|
|
|
|
|
|
ClinVar: RCV000009664, RCV000710390, RCV001831558, RCV003466844, RCV004549354, RCV005042019
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated sporadic cases of persistent hyperinsulinemic hypoglycemia of infancy (HHF1; 256450) due to focal adenomatous hyperplasia, Verkarre et al. (1998) demonstrated loss of heterozygosity of the 11p15 region in the maternal allele and a point mutation in the paternally derived SUR allele: a 4480C-T transition in exon 37 leading to an arg1494-to-trp (R1494W) substitution. The father in each case was heterozygous for the R1494W mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, GLU1506LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852671,
|
|
|
|
|
|
|
|
ClinVar: RCV000009665, RCV000201911
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Finnish family with hyperinsulinemic hypoglycemia (HHF1; 256450), Huopio et al. (2000) identified a heterozygous glu1506-to-lys (E1506K) mutation in the ABCC8 gene. This mutation led to a reduction, but not a complete loss, of K(ATP) channel activity. Huopio et al. (2003) characterized glucose metabolism in adults heterozygous for this mutation. They found that the mutation results in congenital hyperinsulinism in infancy, loss of insulin secretory capacity in early adulthood, and diabetes in middle age. Huopio et al. (2003) suggested that the disorder represents a new subtype of autosomal dominant diabetes. They noted that, except for age at presentation, the E1506K mutation causes a disorder that fulfills the criteria for a form of MODY (see 606391). </p><p>In a 6-year-old girl who was macrosomic at birth and had hyperinsulinemic hypoglycemia, Pinney et al. (2008) identified heterozygosity for what they designated the E1507K mutation in the ABCC8 gene. (Pinney et al., 2008 stated that they used numbering that included the alternatively spliced exon 17 sequence, and therefore the E1506K mutation reported by Huopio et al., 2000 is the same amino acid change as the E1507K mutation reported here.) Pinney et al. (2008) identified the E1507K in 8 other members of the family, none of whom had been suspected of having hypoglycemia, although 3 had severe symptoms, and 3 had mild symptoms consistent with hypoglycemia. The proband's mother and younger brother were the only mutation carriers who denied ever having symptoms of hypoglycemia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 LEUCINE-SENSITIVE HYPOGLYCEMIA OF INFANCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ARG1353HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28936370,
|
|
|
|
|
|
gnomAD: rs28936370,
|
|
|
|
|
|
ClinVar: RCV000009666, RCV001851770, RCV003466845, RCV005042020
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old boy with leucine-sensitive hypoglycemia (LIH; 240800), Magge et al. (2004) identified a 4058G-A transition in exon 33 of the SUR1 gene that resulted in an arg1353-to-his (R1353H) substitution. Arg1353 of SUR1 is conserved across golden hamster, European hamster, rat, mouse, fruit fly, and cricket and is also conserved between human SUR1 and isoforms of SUR2 (601439). Rubidium ion efflux assay and electrophysiologic studies of R1353H SUR1 coexpressed with wildtype Kir6.2 (600937) in simian kidney fibroblasts demonstrated partially impaired ATP-dependent potassium channel function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, VAL187ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852672,
|
|
|
|
|
|
gnomAD: rs137852672,
|
|
|
|
|
|
ClinVar: RCV000009667, RCV000723825, RCV003473071, RCV005042021
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 15 of 24 Finnish patients with hyperinsulinemic hypoglycemia (HHF1; 256450), Otonkoski et al. (1999) identified homozygosity or heterozygosity for a 560T-A transversion in exon 4 of the ABCC8 gene, resulting in a val187-to-asp (V187D) substitution located toward the cytosolic end of the putative fourth or fifth transmembrane domain. In vitro studies demonstrated that the presence of the V187D mutation renders the potassium channel completely nonfunctional. Parents and sibs who were carriers of the mutation were apparently asymptomatic; Otonkoski et al. (1999) postulated the presence of another mutation in heterozygous affected individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, 3-BP DEL, SER1387DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906408,
|
|
|
|
|
|
|
|
ClinVar: RCV000009668, RCV000516204, RCV002243632, RCV002243633
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of the 3-generation family (family 1) with hyperinsulinemic hypoglycemia (HHF1; 256450) originally reported by Thornton et al. (1998), Thornton et al. (2003) identified heterozygosity for a 3-bp deletion (4159-4161) in exon 34 of the ABCC8 gene, resulting in an in-frame deletion of a serine at codon 1387 (ser1387del). The mutation was not found in 4 unaffected family members. Studies in COSm6 cells revealed that potassium channels containing the mutation were not functional. Thornton et al. (2003) noted that this mutation is immediately adjacent to the F1388del (600509.0006) mutation that causes recessive hyperinsulinism in Ashkenazi Jews. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, -64C-G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1395224084,
|
|
|
|
|
|
|
|
ClinVar: RCV000009669, RCV001851771, RCV002254260, RCV002254261, RCV004734507, RCV005042022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant of Spanish descent diagnosed 3 days postnatally with hyperinsulinemic hypoglycemia (HHF1; 256450), Tornovsky et al. (2004) identified heterozygosity for a -64C-G transversion in the promoter of the ABCC8 gene on the paternal allele. Functional studies using a luciferase reporter vector revealed a 40% decrease in reporter gene expression for the mutant variant compared to wildtype, and the variant was not found in 100 control chromosomes tested. No mutation was found on the maternal allele. No focal lesion had been identified after near-total pancreatectomy, but the specimen was not available for reevaluation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 DIABETES MELLITUS, PERMANENT NEONATAL, 3, WITH NEUROLOGIC FEATURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, PHE132LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356637,
|
|
|
|
|
|
|
|
ClinVar: RCV000009670, RCV000020286, RCV001851772, RCV002051781
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 27-year-old man who had permanent neonatal diabetes (PNDM3; 618857) with severe developmental delay and generalized epileptiform activity on EEG, Proks et al. (2006) identified heterozygosity for a de novo 394T-C transition in exon 3 of the ABCC8 gene, resulting in a phe132-to-leu (F132L) substitution. The mutation was not found in his unaffected parents or in 150 normal chromosomes. The authors considered the phenotype in this patient to be a case of DEND (developmental delay, epilepsy, and neonatal diabetes). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 DIABETES MELLITUS, PERMANENT NEONATAL, 3, WITH NEUROLOGIC FEATURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, LEU213ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356642,
|
|
|
|
|
|
|
|
ClinVar: RCV000009671, RCV001089457
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-year-old boy (family 12) with permanent neonatal diabetes mellitus (PNDM3; 618857) and neurologic features, Babenko et al. (2006) identified heterozygosity for a de novo leu213-to-arg (L213R) substitution. The patient's parents reported that he had motor and developmental delays, which were subsequently documented to include dyspraxia. He did not have seizures. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ILE1424VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356653,
|
|
|
|
|
|
|
|
ClinVar: RCV000009672, RCV001089458
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient (family 16) with permanent neonatal diabetes mellitus (PNDM3; 618857), Babenko et al. (2006) identified heterozygosity for a de novo ile1424-to-val (I1424V) substitution. This patient did not have abnormal cognitive function or development. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 DIABETES MELLITUS, TRANSIENT NEONATAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
TYPE 2 DIABETES MELLITUS, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ARG1379CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852673,
|
|
|
|
|
|
gnomAD: rs137852673,
|
|
|
|
|
|
ClinVar: RCV000009673, RCV000009674, RCV000502425, RCV001249022, RCV001851773, RCV004734508
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a French girl (family 19) with transient neonatal diabetes mellitus (TNDM2; 610374) who had a recurrence of diabetes at age 6 and in affected members of an unrelated 5-generation French family (family 17) with transient neonatal diabetes and adult-onset type 2 diabetes mellitus (T2D; 125853), Babenko et al. (2006) identified heterozygosity for an arg1379-to-cys (R1379C) substitution. The mutation arose de novo in the first patient. The 5-year-old female proband of the family had transient neonatal diabetes. Her father developed diabetes at age 32 that was treated with sulfonylureas, and her paternal grandmother was diagnosed with gestational diabetes and treated with diet, and a paternal great-aunt was diagnosed at age 44 with diabetes that was also treated with sulfonylureas. Babenko et al. (2006) proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type 2 diabetes with variable expression and age at onset. </p></div>
|
|
|
|
<p>De Wet et al. (2007) performed functional studies of this mutation, which they designated R1380C, and demonstrated enhanced MgATP hydrolysis by purified isolated fusion proteins of maltose-binding protein and the second nucleotide-binding domain of ABCC8, in which the mutation is located. This increase in ATPase activity reduced the sensitivity of the channel to inhibition by MgATP and increased the whole-cell K(ATP) current. The authors noted that in pancreatic beta cells, such an increase in K(ATP) current would be expected to impair insulin secretion and thereby cause diabetes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 DIABETES MELLITUS, TRANSIENT NEONATAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
TYPE 2 DIABETES MELLITUS, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, LEU582VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852674,
|
|
|
|
|
|
|
|
ClinVar: RCV000009675, RCV000009676
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a 2-year-old French boy (family 36) with transient neonatal diabetes mellitus (TNDM2; 610374) and in affected members of an unrelated 3-generation French family (family 16) with transient neonatal diabetes and adult-onset type 2 diabetes mellitus (T2D; 125853), Babenko et al. (2006) identified heterozygosity for a leu583-to-val (L582V) substitution. The mutation arose de novo in the first patient. In the affected family, the 5-year-old male proband and his female cousin had transient neonatal diabetes, whereas their mutation-positive fathers both developed after age 30 adult-onset type 2 diabetes that was treated with diet alone; and their paternal grandfather also had type 2 diabetes occurring later in life. Babenko et al. (2006) proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type 2 diabetes with variable expression and age at onset. </p></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ASN72SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356634,
|
|
|
|
|
|
|
|
ClinVar: RCV000009677, RCV001089459, RCV003473072
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient from a cohort of 59 patients with permanent neonatal diabetes (PNDM3; 618857) who received a diagnosis before 6 months of age and who did not have a KCNJ11 mutation, Ellard et al. (2007) identified a 215A-G transition in the ABCC8 gene, resulting in an asn72-to-ser (N72S) substitution, in combination with mosaic segmental paternal isodisomy for 11pter to 11p14. This region includes the ABCC8 gene, and thus uniparental disomy had unmasked a recessively acting mutation. The father was heterozygous for the mutation but did not have diabetes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, GLU382LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356651,
|
|
|
|
|
|
|
|
ClinVar: RCV000009678, RCV001089460
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with permanent neonatal diabetes mellitus (PNDM3; 618857), diagnosed before the age of 6 months, Ellard et al. (2007) identified a homozygous 1144G-A transition in the ABCC8 gene that resulted in a glu382-to-lys (E382K) substitution. The heterozygous, first-cousin parents were not diabetic. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, ALA1185GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193929369,
|
|
|
|
|
|
|
|
ClinVar: RCV000009679, RCV001089461, RCV002243634, RCV002243635
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with permanent neonatal diabetes mellitus (PNDM3; 618857), diagnosed before the age of 6 months, the offspring of first cousins, Ellard et al. (2007) identified a homozygous mutation in the ABCC8 gene: a 3554C-A transversion resulting in an ala1185-to-glu substitution (A1185E). Neither parent was diabetic. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, 134C-T, PRO45LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606623,
|
|
|
|
|
|
|
|
ClinVar: RCV000009680, RCV002512948
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with permanent neonatal diabetes mellitus (PNDM3; 618857), Ellard et al. (2007) observed compound heterozygosity for mutations in the ABCC8 gene. One allele carried a 134C-T transition resulting in a pro45-to-leu substitution (P45L); the other carried a 4201G-A transition resulting in a gly1401-to-arg substitution (G1401R; 600509.0025). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, GLY1401ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852676,
|
|
|
|
|
|
gnomAD: rs137852676,
|
|
|
|
|
|
ClinVar: RCV000009657, RCV000029263, RCV001277179, RCV001390783, RCV003321485, RCV003466873, RCV005042088
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gly1401-to-arg (G1401R) mutation in the ABCC8 gene that was found in compound heterozygous state in a patient with permanent neonatal diabetes mellitus (PNDM3; 618857) by Ellard et al. (2007), see 600509.0024. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 DIABETES MELLITUS, PERMANENT NEONATAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, 257T-G, VAL86GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193929360,
|
|
|
|
|
|
|
|
ClinVar: RCV000009681, RCV001089462
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with permanent neonatal diabetes mellitus (PNDM3; 618857) diagnosed at the age of 5 months, Ellard et al. (2007) found heterozygosity for a mutation in the ABCC8 gene: a 257T-G transversion resulting in a val86-to-gly substitution (V86G). This was one of 8 patients with this disorder associated with a heterozygous de novo mutation in ABCC8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, EX13DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000032666
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male proband with diazoxide-unresponsive hyperinsulinemic hypoglycemia (HHF1; 256450), who had undergone near-total pancreatectomy and in whom a heterozygous 1-bp duplication (512dupT; 600509.0028) had previously been detected by Banerjee et al. (2011), Flanagan et al. (2012) used MPLA and found that the patient also carried a heterozygous deletion of exon 13 in the ABCC8 gene. His unaffected parents were each heterozygous for 1 of the mutations. Flanagan et al. (2012) also identified heterozygosity for the ABCC8 exon 13 deletion in another male proband who had undergone near-total pancreatectomy, histologic examination of which revealed normal pancreatic tissue, consistent with a focal lesion. The deletion was inherited from his unaffected father; pancreatic tissue was not available for loss-of-heterozygosity studies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, 1-BP DUP, 512T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1564980510,
|
|
|
|
|
|
|
|
ClinVar: RCV000032667, RCV002254153, RCV002254154
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp duplication in the ABCC8 gene (512dupT) that was found in a patient with diazoxide-unresponsive hyperinsulinemic hypoglycemia (HHF1; 256450) by Banerjee et al. (2011) and Flanagan et al. (2012), see 600509.0027. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCC8, IVS8, A-G, -1013
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs980458021,
|
|
|
|
|
|
|
|
ClinVar: RCV000032668, RCV001211946, RCV003466885, RCV005042102
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In 5 probands with diazoxide-unresponsive hypoglycemia due to focal hyperinsulinism (HHF1; 256450), Flanagan et al. (2013) identified heterozygosity for a c.1333-1013A-G transition (c.1333-1013A-G, NM_000352.3) deep within intron 8 of the ABCC8 gene, creating a cryptic splice donor site that results in the inclusion of an out-of-frame 76-bp pseudoexon and premature termination. The mutation was inherited from the father in 4 of the patients; in the fifth patient, the mutation was not found in the mother but no DNA was available from the father. The variant was also identified in homozygosity in 1 patient with diffuse hyperinsulinism diagnosed on postmortem examination, and was present in heterozygosity in both parents. Chromosome 11 microsatellite analysis revealed a shared haplotype among the 6 patients, 4 of whom were from Ireland, suggesting that the variant represents a founder mutation in the Irish population. </p></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aguilar-Bryan, L., Nichols, C. G., Wechsler, S. W., Clement, J. P., IV, Boyd, A. E., III, Gonzalez, G., Herrera-Sosa, H., Nguy, K., Bryan, J., Nelson, D. A.
|
|
<strong>Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.</strong>
|
|
Science 268: 423-426, 1995.
|
|
|
|
|
|
[PubMed: 7716547]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7716547]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P.
|
|
<strong>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</strong>
|
|
New Eng. J. Med. 355: 456-466, 2006.
|
|
|
|
|
|
[PubMed: 16885549]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa055068]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Banerjee, I., Skae, M., Flanagan, S. E., Rigby, L., Patel, L., Didi, M., Blair, J., Ehtisham, S., Ellard, S., Cosgrove, K. E.
|
|
<strong>The contribution of rapid K(ATP) channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.</strong>
|
|
Europ. J. Endocr. 164: 733-740, 2011.
|
|
|
|
|
|
[PubMed: 21378087]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1530/EJE-10-1136]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellanne-Chantelot, C., Saint-Martin, C., Ribeiro, M.-J., Vaury, C., Verkarre, V., Arnoux, J.-B., Valayannopoulos, V., Gobrecht, S., Sempoux, C., Rahier, J., Fournet, J.-C., Jaubert, F., Aigrain, Y., Nihoul-Fekete, C., de Lonlay, P.
|
|
<strong>ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.</strong>
|
|
J. Med. Genet. 47: 752-759, 2010.
|
|
|
|
|
|
[PubMed: 20685672]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2009.075416]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Lonlay, P., Fournet, J.-C., Rahier, J., Gross-Morand, M.-S., Poggi-Travert, F., Foussier, V., Bonnefont, J.-P., Brusset, M.-C., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C.
|
|
<strong>Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.</strong>
|
|
J. Clin. Invest. 100: 802-807, 1997.
|
|
|
|
|
|
[PubMed: 9259578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI119594]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Wet, H., Rees, M. G., Shimomura, K., Aittoniemi, J., Patch, A.-M., Flanagan, S. E., Ellard, S., Hattersley, A. T., Sansom, M. S. P., Ashcroft, F. M.
|
|
<strong>Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 18988-18992, 2007.
|
|
|
|
|
|
[PubMed: 18025464]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0707428104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dunne, M. J., Kane, C., Shepherd, R. M., Sanchez, J. A., James, R. F. L., Johnson, P. R. V., Aynsley-Green, A., Lu, S., Clement, J. P., IV, Lindley, K. J., Seino, S., Aguilar-Bryan, L.
|
|
<strong>Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor.</strong>
|
|
New Eng. J. Med. 336: 703-706, 1997.
|
|
|
|
|
|
[PubMed: 9041101]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199703063361005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellard, S., Flanagan, S. E., Girard, C. A., Patch, A.-M., Harries, L. W., Parrish, A., Edghill, E. L., Mackay, D. J. G., Proks, P., Shimomura, K., Haberland, H., Carson, D. J., Shield, J. P. H., Hattersley, A. T., Ashcroft, F. M.
|
|
<strong>Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.</strong>
|
|
Am. J. Hum. Genet. 81: 375-382, 2007.
|
|
|
|
|
|
[PubMed: 17668386]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/519174]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fantes, J. A., Oghene, K., Boyle, S., Danes, S., Fletcher, J. M., Bruford, E. A., Williamson, K., Seawright, A., Schedl, A., Hanson, I., Zehetner, G., Bhogal, R., Lehrach, H., Gregory, S., Williams, J., Little, P. F. R., Sellar, G. C., Hoovers, J., Mannens, M., Weissenbach, J., Junien, C., van Heyningen, V., Bickmore, W. A.
|
|
<strong>A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.</strong>
|
|
Genomics 25: 447-461, 1995.
|
|
|
|
|
|
[PubMed: 7789978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80045-n]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Flanagan, S. E., Damhuis, A., Bannerjee, I., Rokicki, D., Jefferies, C., Kapoor, R. R., Hussain, K., Ellard, S.
|
|
<strong>Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.</strong>
|
|
Pediat. Diabetes 13: 285-289, 2012.
|
|
|
|
|
|
[PubMed: 21978130]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-5448.2011.00821.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Flanagan, S. E., Xie, W., Caswell, R., Damhuis, A., Vianey-Saban, C., Akcay, T., Darendeliler, F., Bas, F., Guven, A., Siklar, Z., Ocal, G., Berberoglu, M., and 9 others.
|
|
<strong>Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.</strong>
|
|
Am. J. Hum. Genet. 92: 131-136, 2013.
|
|
|
|
|
|
[PubMed: 23273570]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.11.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giurgea, I., Sempoux, C., Bellanne-Chantelot, C., Ribeiro, M., Hubert, L., Boddaert, N., Saudubray, J.-M., Robert, J.-J., Brunelle, F., Rahier, J., Jaubert, F., Nihoul-Fekete, C., de Lonlay, P.
|
|
<strong>The Knudson's two-hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism.</strong>
|
|
J. Clin. Endocr. Metab. 91: 4118-4123, 2006.
|
|
|
|
|
|
[PubMed: 16882742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2006-0397]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Glaser, B., Chiu, K. C., Anker, R., Nestorowicz, A., Landau, H., Ben-Bassat, H., Shlomai, Z., Kaiser, N., Thornton, P. S., Stanley, C. A., Spielman, R. S., Gogolin-Ewens, K., Cerasi, E., Baker, L., Rice, J., Donis-Keller, H., Permutt, M. A.
|
|
<strong>Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene.</strong>
|
|
Nature Genet. 7: 185-188, 1994.
|
|
|
|
|
|
[PubMed: 7920639]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0694-185]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Glaser, B., Furth, J., Stanley, C. A., Baker, L., Thornton, P. S., Landau, H., Permutt, M. A.
|
|
<strong>Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.</strong>
|
|
Hum. Mutat. 14: 23-29, 1999.
|
|
|
|
|
|
[PubMed: 10447255]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<23::AID-HUMU3>3.0.CO;2-#]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Glaser, B., Ryan, F., Donath, M., Landau, H., Stanley, C. A., Baker, L., Barton, D. E., Thornton, P. S.
|
|
<strong>Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene.</strong>
|
|
Diabetes 48: 1652-1657, 1999.
|
|
|
|
|
|
[PubMed: 10426386]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diabetes.48.8.1652]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goksel, D. L., Fischbach, K., Duggirala, R., Mitchell, B. D., Aguilar-Bryan, L., Blangero, J., Stern, M. P., O'Connell, P.
|
|
<strong>Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.</strong>
|
|
Hum. Genet. 103: 280-285, 1998.
|
|
|
|
|
|
[PubMed: 9799081]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050817]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gribble, F. M., Tucker, S. J., Ashcroft, F. M.
|
|
<strong>The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.</strong>
|
|
EMBO J. 16: 1145-1152, 1997.
|
|
|
|
|
|
[PubMed: 9135131]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/16.6.1145]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Henwood, M. J., Kelly, A., MacMullen, C., Bhatia, P., Ganguly, A., Thornton, P. S., Stanley, C. A.
|
|
<strong>Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.</strong>
|
|
J. Clin. Endocr. Metab. 90: 789-794, 2005.
|
|
|
|
|
|
[PubMed: 15562009]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-1604]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huopio, H., Otonkoski, T., Vauhkonen, I., Reimann, F., Ashcroft, F. M., Laakso, M.
|
|
<strong>A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. (Commentary)</strong>
|
|
Lancet 361: 301-307, 2003.
|
|
|
|
|
|
[PubMed: 12559865]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(03)12325-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huopio, H., Reimann, F., Ashfield, R., Komulainen, J., Lenko, H.-L., Rahier, J., Vauhkonen, I., Kere, J., Laakso, M., Ashcroft, F., Otonkoski, T.
|
|
<strong>Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.</strong>
|
|
J. Clin. Invest. 106: 897-906, 2000.
|
|
|
|
|
|
[PubMed: 11018078]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI9804]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Inagaki, N., Gonoi, T., Clement, J. P., IV., Namba, N., Inazawa, J., Gonzalez, G., Aguilar-Bryan, L., Seino, S., Bryan, J.
|
|
<strong>Reconstitution of I(KATP): an inward rectifier subunit plus the sulfonylurea receptor.</strong>
|
|
Science 270: 1166-1169, 1995.
|
|
|
|
|
|
[PubMed: 7502040]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.270.5239.1166]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Inoue, H., Ferrer, J., Welling, C. M., Elbein, S. C., Hoffman, M., Mayorga, R., Warren-Perry, M., Zhang, Y., Millns, H., Turner, R., Province, M., Bryan, J., Permutt, M. A., Aguilar-Bryan, L.
|
|
<strong>Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.</strong>
|
|
Diabetes 45: 825-831, 1996.
|
|
|
|
|
|
[PubMed: 8635661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.45.6.825]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laukkanen, O., Pihlajamaki, J., Lindstrom, J., Eriksson, J., Valle, T. T., Hamalainen, H., Ilanne-Patrikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J., Uusitupa, M., Laakso, M., Finnish Diabetes Prevention Study Group.
|
|
<strong>Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.</strong>
|
|
J. Clin. Endocr. Metab. 89: 6286-6290, 2004.
|
|
|
|
|
|
[PubMed: 15579791]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-1204]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., Hirschhorn, J. N.
|
|
<strong>Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease.</strong>
|
|
Nature Genet. 33: 177-182, 2003.
|
|
|
|
|
|
[PubMed: 12524541]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1071]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Magge, S. N., Shyng, S.-L., MacMullen, C., Steinkrauss, L., Ganguly, A., Katz, L. E. L., Stanley, C. A.
|
|
<strong>Familial leucine-sensitive hypoglycemia in infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.</strong>
|
|
J. Clin. Endocr. Metab. 89: 4450-4456, 2004.
|
|
|
|
|
|
[PubMed: 15356046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-0441]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuo, M., Trapp, S., Tanizawa, Y., Kioka, N., Amachi, T., Oka, Y., Ashcroft, F. M., Ueda, K.
|
|
<strong>Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
J. Biol. Chem. 275: 41184-41191, 2000.
|
|
|
|
|
|
[PubMed: 10993895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M006503200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meirhaeghe, A., Helbecque, N., Cottel, D., Arveiler, D., Ruidavets, J.-B., Haas, B., Ferrieres, J., Tauber, J.-P., Bingham, A., Amouyel, P.
|
|
<strong>Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study.</strong>
|
|
Am. J. Med. Genet. 101: 4-8, 2001.
|
|
|
|
|
|
[PubMed: 11343328]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1297]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nestorowicz, A., Glaser, B., Wilson, B. A., Shyng, S.-L., Nichols, C. G., Stanley, C. A., Thornton, P. S., Permutt, M. A.
|
|
<strong>Genetic heterogeneity in familial hyperinsulinism.</strong>
|
|
Hum. Molec. Genet. 7: 1119-1128, 1998. Note: Erratum: Hum. Molec. Genet. 7: 1527 only, 1998.
|
|
|
|
|
|
[PubMed: 9618169]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.7.1119]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nestorowicz, A., Wilson, B. A., Schoor, K. P., Inoue, H., Glaser, B., Landau, H., Stanley, C. A., Thornton, P. S., Clement, J. P., IV, Bryan, J., Aguilar-Bryan, L., Permutt, M. A.
|
|
<strong>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</strong>
|
|
Hum. Molec. Genet. 5: 1813-1822, 1996.
|
|
|
|
|
|
[PubMed: 8923011]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.11.1813]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otonkoski, T., Ammala, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K., Ashfield, R., Huang, E., Komulainen, J., Ashcroft, F. M., Dunne, M. J., Kere, J., Thomas, P. M.
|
|
<strong>A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.</strong>
|
|
Diabetes 48: 408-415, and 415, 1999.
|
|
|
|
|
|
[PubMed: 10334322]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diabetes.48.2.408]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Philipson, L. H., Steiner, D. F.
|
|
<strong>Pas de deux or more: the sulfonylurea receptor and K+ channels.</strong>
|
|
Science 268: 372-373, 1995.
|
|
|
|
|
|
[PubMed: 7716539]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7716539]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pinney, S. E., MacMullen, C., Becker, S., Lin, Y.-W., Hanna, C., Thornton, P., Ganguly, A., Shyng, S.-L., Stanley, C. A.
|
|
<strong>Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant K(ATP) channel mutations.</strong>
|
|
J. Clin. Invest. 118: 2877-2886, 2008.
|
|
|
|
|
|
[PubMed: 18596924]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI35414]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., Rossetti, L.
|
|
<strong>Hypothalamic K(ATP) channels control hepatic glucose production.</strong>
|
|
Nature 434: 1026-1031, 2005.
|
|
|
|
|
|
[PubMed: 15846348]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature03439]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Proks, P., Arnold, A. L., Bruining, J., Girard, C., Flanagan, S. E., Larkin, B., Colclough, K., Hattersley, A. T., Ashcroft, F. M., Ellard, S.
|
|
<strong>A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.</strong>
|
|
Hum. Molec. Genet. 15: 1793-1800, 2006.
|
|
|
|
|
|
[PubMed: 16613899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddl101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reis, A. F., Ye, W.-Z., Dubois-Laforgue, D., Bellanne-Chantelot, C., Timsit, J., Velho, G.
|
|
<strong>Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians.</strong>
|
|
Hum. Genet. 107: 138-144, 2000.
|
|
|
|
|
|
[PubMed: 11030411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390000345]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ryan, F., Devaney, D., Joyce, C., Nestorowicz, A., Permutt, M. A., Glaser, B., Barton, D. E., Thornton, P. S.
|
|
<strong>Hyperinsulinism: molecular aetiology of focal disease.</strong>
|
|
Arch. Dis. Child 79: 445-447, 1998.
|
|
|
|
|
|
[PubMed: 10193261]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.79.5.445]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Simard, J. M., Chen, M., Tarasov, K. V., Bhatta, S., Ivanova, S., Melnitchenko, L., Tsymbalyuk, N., West, G. A., Gerzanich, V.
|
|
<strong>Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.</strong>
|
|
Nature Med. 12: 433-440, 2006.
|
|
|
|
|
|
[PubMed: 16550187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm1390]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, P. M., Cote, G. J., Hallman, D. M., Mathew, P. M.
|
|
<strong>Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
Am. J. Hum. Genet. 56: 416-421, 1995.
|
|
|
|
|
|
[PubMed: 7847376]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., Bryan, J.
|
|
<strong>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
Science 268: 426-429, 1995.
|
|
|
|
|
|
[PubMed: 7716548]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7716548]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomas, P. M., Wohllk, N., Huang, E., Kuhnle, U., Rabl, W., Gagel, R. F., Cote, G. J.
|
|
<strong>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</strong>
|
|
Am. J. Hum. Genet. 59: 510-518, 1996.
|
|
|
|
|
|
[PubMed: 8751851]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thornton, P. S., MacMullen, C., Ganguly, A., Ruchelli, E., Steinkrauss, L., Crane, A., Aguilar-Bryan, L., Stanley, C. A.
|
|
<strong>Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.</strong>
|
|
Diabetes 52: 2403-2410, 2003.
|
|
|
|
|
|
[PubMed: 12941782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diabetes.52.9.2403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thornton, P. S., Satin-Smith, M. S., Herold, K., Glaser, B., Chiu, K. C., Nestorowicz, A., Permutt, M. A., Baker, L., Stanley, C. A.
|
|
<strong>Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.</strong>
|
|
J. Pediat. 132: 9-14, 1998.
|
|
|
|
|
|
[PubMed: 9469993]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(98)70477-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tornovsky, S., Crane, A., Cosgrove, K. E., Hussain, K., Lavie, J., Heyman, M., Nesher, Y., Kuchinski, N., Ben-Shushan, E., Shatz, O., Nahari, E., Potikha, T., and 11 others.
|
|
<strong>Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.</strong>
|
|
J. Clin. Endocr. Metab. 89: 6224-6234, 2004.
|
|
|
|
|
|
[PubMed: 15579781]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2004-1233]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verkarre, V., Fournet, J.-C., de Lonlay, P., Gross-Morand, M.-S., Devillers, M., Rahier, J., Brunelle, F., Robert, J.-J., Nihoul-Fekete, C., Saudubray, J.-M., Junien, C.
|
|
<strong>Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.</strong>
|
|
J. Clin. Invest. 102: 1286-1291, 1998.
|
|
|
|
|
|
[PubMed: 9769320]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI4495]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 06/13/2018<br>Marla J. F. O'Neill - updated : 2/4/2013<br>Marla J. F. O'Neill - updated : 3/20/2009<br>Marla J. F. O'Neill - updated : 5/16/2008<br>Victor A. McKusick - updated : 7/26/2007<br>John A. Phillips, III - updated : 7/13/2007<br>John A. Phillips, III - updated : 8/22/2006<br>Marla J. F. O'Neill - updated : 8/11/2006<br>Cassandra L. Kniffin - updated : 5/15/2006<br>Marla J. F. O'Neill - updated : 3/22/2006<br>Marla J. F. O'Neill - updated : 3/21/2006<br>Marla J. F. O'Neill - updated : 3/16/2006<br>Ada Hamosh - updated : 5/3/2005<br>John A. Phillips, III - updated : 4/21/2005<br>Anne M. Stumpf - reorganized : 4/21/2005<br>Victor A. McKusick - updated : 3/10/2003<br>Victor A. McKusick - updated : 1/30/2003<br>Victor A. McKusick - updated : 5/16/2001<br>Paul J. Converse - updated : 3/27/2001<br>John A. Phillips, III - updated : 11/8/2000<br>Victor A. McKusick - updated : 9/14/2000<br>Victor A. McKusick - updated : 8/16/1999<br>Ada Hamosh - updated : 3/18/1999<br>Victor A. McKusick - updated : 10/16/1998<br>Victor A. McKusick - updated : 7/8/1998<br>Victor A. McKusick - updated : 2/27/1998<br>Victor A. McKusick - updated : 4/11/1997<br>Moyra Smith - updated : 1/31/1997<br>Perseveranda M. Cagas - updated : 9/23/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 4/28/1995
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 02/25/2025<br>carol : 02/25/2025<br>carol : 02/25/2025<br>alopez : 02/24/2025<br>alopez : 12/01/2020<br>carol : 05/04/2020<br>alopez : 04/30/2020<br>alopez : 04/30/2020<br>alopez : 04/30/2020<br>carol : 03/05/2019<br>alopez : 06/13/2018<br>carol : 12/20/2017<br>carol : 07/21/2017<br>carol : 09/12/2016<br>joanna : 07/01/2016<br>mcolton : 6/11/2015<br>carol : 3/10/2015<br>alopez : 9/4/2014<br>carol : 2/4/2013<br>terry : 7/6/2012<br>wwang : 3/30/2009<br>terry : 3/20/2009<br>carol : 5/16/2008<br>alopez : 7/30/2007<br>terry : 7/26/2007<br>alopez : 7/13/2007<br>alopez : 11/21/2006<br>alopez : 11/21/2006<br>carol : 9/5/2006<br>joanna : 8/31/2006<br>alopez : 8/22/2006<br>wwang : 8/16/2006<br>terry : 8/11/2006<br>wwang : 5/24/2006<br>ckniffin : 5/15/2006<br>carol : 3/23/2006<br>carol : 3/22/2006<br>carol : 3/21/2006<br>carol : 3/20/2006<br>carol : 3/16/2006<br>carol : 3/16/2006<br>joanna : 11/4/2005<br>alopez : 5/10/2005<br>terry : 5/3/2005<br>alopez : 4/21/2005<br>alopez : 4/21/2005<br>alopez : 4/21/2005<br>terry : 5/15/2003<br>tkritzer : 5/7/2003<br>carol : 3/17/2003<br>carol : 3/17/2003<br>tkritzer : 3/13/2003<br>terry : 3/10/2003<br>alopez : 1/31/2003<br>terry : 1/30/2003<br>mcapotos : 5/23/2001<br>mcapotos : 5/22/2001<br>terry : 5/16/2001<br>mgross : 3/27/2001<br>alopez : 3/22/2001<br>terry : 11/8/2000<br>carol : 10/17/2000<br>mcapotos : 10/5/2000<br>mcapotos : 9/26/2000<br>terry : 9/14/2000<br>carol : 11/10/1999<br>carol : 11/9/1999<br>jlewis : 8/24/1999<br>terry : 8/16/1999<br>terry : 8/16/1999<br>jlewis : 8/16/1999<br>alopez : 3/18/1999<br>alopez : 3/18/1999<br>carol : 10/28/1998<br>terry : 10/16/1998<br>carol : 7/13/1998<br>terry : 7/8/1998<br>terry : 6/4/1998<br>carol : 3/28/1998<br>alopez : 2/27/1998<br>terry : 2/27/1998<br>mark : 4/11/1997<br>mark : 4/11/1997<br>alopez : 4/2/1997<br>terry : 4/1/1997<br>mark : 1/31/1997<br>terry : 1/31/1997<br>mark : 1/30/1997<br>terry : 11/14/1996<br>terry : 9/25/1996<br>mark : 9/23/1996<br>mark : 11/16/1995<br>mimadm : 11/3/1995<br>terry : 6/26/1995<br>terry : 5/3/1995<br>mark : 4/28/1995
|
|
</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>
|
|
|
|
|