3991 lines
374 KiB
Text
3991 lines
374 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
|
|
|
|
- #162000 - TUBULOINTERSTITIAL KIDNEY DISEASE, AUTOSOMAL DOMINANT 1; ADTKD1
|
|
|
|
|
|
- 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=162000"><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">#162000</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/162000"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS162000"> <strong>Phenotypic Series</strong> </a>
|
|
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#nomenclature">Nomenclature</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=TUBULOINTERSTITIAL KIDNEY DISEASE, AUTOSOMAL DOMINANT" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
|
|
<div id="mimEuroGentestFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10332&Typ=Pat" title="Autosomal dominant tubulointerstitial kidney disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Autosomal dominant tubuloi… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11882&Typ=Pat" title="UMOD-related autosomal dominant tubulointerstitial kidney disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">UMOD-related autosomal dom… </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1356/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/8400" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/condition/autosomal-dominant-tubulointerstitial-kidney-disease-umod" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=162000[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
|
|
<div id="mimOrphanetFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=34149" title="Autosomal dominant tubulointerstitial kidney disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Autosomal dominant tubuloi…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=88950" title="UMOD-related autosomal dominant tubulointerstitial kidney disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">UMOD-related autosomal dom…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:0060062" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/disease/162000" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0060062" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</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>ORPHA:</strong> 34149, 88950<br />
|
|
|
|
|
|
<strong>DO:</strong> 0060062<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
162000
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
<div class="mim-changed mim-change">TUBULOINTERSTITIAL KIDNEY DISEASE, AUTOSOMAL DOMINANT 1; ADTKD1</div>
|
|
|
|
</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">
|
|
HYPERURICEMIC NEPHROPATHY, FAMILIAL JUVENILE, 1; HNFJ1<br />
|
|
FAMILIAL JUVENILE HYPERURICEMIC NEPHROPATHY; FJHN<br />
|
|
GOUTY NEPHROPATHY, FAMILIAL JUVENILE<br />
|
|
MEDULLARY CYSTIC KIDNEY DISEASE 2; MCKD2<br />
|
|
MEDULLARY CYSTIC KIDNEY DISEASE 2, AUTOSOMAL DOMINANT; ADMCKD2<br />
|
|
GLOMERULOCYSTIC KIDNEY DISEASE WITH HYPERURICEMIA AND ISOSTHENURIA
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/16/243?start=-3&limit=10&highlight=243">
|
|
16p12.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Tubulointerstitial kidney disease, autosomal dominant, 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162000"> 162000 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
UMOD
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191845"> 191845 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/162000" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS162000" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/162000" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/162000" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Vascular </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Arterial hypertension (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38341003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38341003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/401-405.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">401-405.99</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/997.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">997.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020538&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020538</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000822" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000822</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000822" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000822</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Kidneys </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Renal insufficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/723188008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">723188008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42399005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42399005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/236423003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">236423003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N19" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N19</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/586" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">586</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1565489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1565489</a>, <a href="https://bioportal.bioontology.org/search?q=C0035078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035078</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000083" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000083</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000083" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000083</a>]</span><br /> -
|
|
Nephropathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90708001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90708001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N28.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N28.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N08" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N08</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022658&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022658</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000112" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000112</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000112" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000112</a>]</span><br /> -
|
|
Renal failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42399005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42399005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N19" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N19</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/586" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">586</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035078</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000083" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000083</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000083" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000083</a>]</span><br /> -
|
|
Polydipsia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17173007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17173007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/139104001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">139104001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085602&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085602</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001959" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001959</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001959" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001959</a>]</span><br /> -
|
|
Polyuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56574000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56574000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/28442001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">28442001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/718402002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">718402002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R35.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R35.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0032617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0032617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000103" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000103</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000103" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000103</a>]</span><br /> -
|
|
Impaired urinary concentration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542212&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542212</a>]</span><br /> -
|
|
Chronic interstitial nephritis seen on renal biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542213&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542213</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60926001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60926001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N11</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N11.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N11.9</a>]</span><br /> -
|
|
Tubulointerstitial abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4025732&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4025732</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001969" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001969</a>]</span><br /> -
|
|
Tubular atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858395&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858395</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000092" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000092</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000092" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000092</a>]</span><br /> -
|
|
Interstitial fibrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/125565008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">125565008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887486&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887486</a>]</span><br /> -
|
|
Hyaline material deposited around tubules <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542214</a>]</span><br /> -
|
|
Thickening of the basement membrane <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/125483003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">125483003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0544995&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0544995</a>]</span><br /> -
|
|
Medullary cysts (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315960&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315960</a>]</span><br /> -
|
|
Glomerulosclerosis (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/82646005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">82646005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197661001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197661001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1417247&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1417247</a>, <a href="https://bioportal.bioontology.org/search?q=C0178664&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0178664</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000096" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000096</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000096" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000096</a>]</span><br /> -
|
|
Glomerulocystic kidney disease (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4020705&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4020705</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100611" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100611</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100611" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100611</a>]</span><br /> -
|
|
Dilatation of Bowman space in glomeruli <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542215&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542215</a>]</span><br /> -
|
|
Rudimentary glomerular tufts <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542216&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542216</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> METABOLIC FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Gout <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90560007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90560007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M10</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M10.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M10.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/274.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">274.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">274</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018099&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018099</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001997" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001997</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001997" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001997</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hyperuricemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35885006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35885006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740394</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002149" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002149</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002149" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002149</a>]</span><br /> -
|
|
Decreased urinary excretion of uromodulin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805786</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset of hyperuricemia or gout in young adulthood<br /> -
|
|
Slowly progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854494&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854494</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003677</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003677</a>]</span><br /> -
|
|
Highly variable phenotype, even within families <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866210&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866210</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the uromodulin gene (UMOD, <a href="/entry/191845#0001">191845.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Tubulointerstitial kidney disease
|
|
- <a href="/phenotypicSeries/PS162000">PS162000</a>
|
|
- 6 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1214?start=-3&limit=10&highlight=1214"> 1q22 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174000"> Tubulointerstitial kidney disease, autosomal dominant, 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174000"> 174000 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/158340"> MUC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/158340"> 158340 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1606?start=-3&limit=10&highlight=1606"> 1q32.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613092"> Tubulointerstitial kidney disease, autosomal dominant, 4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613092"> 613092 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/179820"> REN </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/179820"> 179820 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/647?start=-3&limit=10&highlight=647"> 3q21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617056"> Tubulointerstitial kidney disease, autosomal dominant, 5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617056"> 617056 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609213"> SEC61A1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609213"> 609213 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/958?start=-3&limit=10&highlight=958"> 11q23.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/621106"> Tubulointerstitial kidney disease, autosomal dominant 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/621106"> 621106 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107690"> APOA4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107690"> 107690 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/16/243?start=-3&limit=10&highlight=243"> 16p12.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162000"> Tubulointerstitial kidney disease, autosomal dominant, 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162000"> 162000 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191845"> UMOD </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191845"> 191845 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/459?start=-3&limit=10&highlight=459"> 17q12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/137920"> Renal cysts and diabetes syndrome </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/137920"> 137920 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/189907"> HNF1B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/189907"> 189907 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that autosomal dominant tubulointerstitial kidney disease-1 (ADTKD1) is caused by heterozygous mutation in the gene encoding uromodulin (UMOD; <a href="/entry/191845">191845</a>) on chromosome 16p12.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>Autosomal dominant tubulointerstitial kidney disease-1 (ADTKD1) is an adult-onset, slowly progressive renal disease characterized by elevated serum uric acid (hyperuricemia) due to low fractional excretion of uric acid, defective urinary concentrating ability, 'bland' urinary sediment, and progression to end-stage renal failure. Some patients may develop gouty arthritis, arterial hypertension, polydipsia/polyuria, or mild proteinuria. The onset of symptoms is usually in the third or fourth decade, although earlier and later onset have been reported. Renal ultrasound may show small or hyperechogenic kidneys. Renal biopsy shows variable abnormalities, including tubular atrophy, interstitial fibrosis, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. The median age at onset of end-stage renal disease (ESRD) is 56 years (range 50-65). There is significant inter- and intrafamilial variability, as well as incomplete penetrance, which hampers diagnosis (summary by <a href="#9" class="mim-tip-reference" title="Hart, T. C., Gorry, M. C., Hart, P. S., Woodard, A. S., Shihabi, Z., Sandhu, J., Shirts, B., Xu, L., Zhu, H., Barmada, M. M., Bleyer, A. J. <strong>Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.</strong> J. Med. Genet. 39: 882-892, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471200</a>] [<a href="https://doi.org/10.1136/jmg.39.12.882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471200">Hart et al., 2002</a>, <a href="#1" class="mim-tip-reference" title="Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R. <strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong> Am. J. Kidney Dis. 72: 411-418, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29784615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29784615</a>] [<a href="https://doi.org/10.1053/j.ajkd.2018.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29784615">Ayasreh et al., 2018</a>, and <a href="#6" class="mim-tip-reference" title="Devuyst, O., Olinger, E., Weber, S., Eckardt, K.-U., Kmoch, S., Rampoldi, L., Bleyer, A. J. <strong>Autosomal dominant tubulointerstitial kidney disease.</strong> Nat. Rev. Dis. Primers. 5: 60, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488840</a>] [<a href="https://doi.org/10.1038/s41572-019-0109-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488840">Devuyst et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29784615+31488840+12471200" 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>Genetic Heterogeneity of Autosomal Dominant Tubulointerstitial Kidney Disease</em></strong>
|
|
</p>
|
|
|
|
<div class="mim-changed mim-change"><p>ADTKD2 (<a href="/entry/174000">174000</a>) is caused by mutation in the MUC1 gene (<a href="/entry/158340">158340</a>) on chromosome 1q22; ADTKD3 (<a href="/entry/137920">137920</a>) is caused by mutation in the HNF1B gene (<a href="/entry/189907">189907</a>) on chromosome 17q12; ADTKD4 (<a href="/entry/613092">613092</a>) is caused by mutation in the renin gene (REN; <a href="/entry/179820">179820</a>) on chromosome 1q32; ADTKD5 (<a href="/entry/617056">617056</a>) is caused by mutation in the SEC61A1 gene (<a href="/entry/609213">609213</a>) on chromosome 3q21; and ADTKD6 (<a href="/entry/621106">621106</a>) is caused by mutation in the APOA4 gene (<a href="/entry/107690">107690</a>) on chromosome 11q23.</p></div>
|
|
|
|
<p>See <a href="/entry/614227">614227</a> for a possibly distinct form of ADTKD tentatively mapped to chromosome 2p22.1-p21.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="nomenclature" class="mim-anchor"></a>
|
|
<h4 href="#mimNomenclatureFold" id="mimNomenclatureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimNomenclatureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimNomenclatureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The terms 'familial juvenile hyperuricemic nephropathy' (FJHN, HNFJ), 'medullary cystic kidney disease' (MCKD), 'glomerulocystic kidney disease' (GCKD), 'tubulointerstitial nephritis,' and 'hereditary interstitial kidney disease,' among others, have all been used to describe this phenotype. In a review, <a href="#6" class="mim-tip-reference" title="Devuyst, O., Olinger, E., Weber, S., Eckardt, K.-U., Kmoch, S., Rampoldi, L., Bleyer, A. J. <strong>Autosomal dominant tubulointerstitial kidney disease.</strong> Nat. Rev. Dis. Primers. 5: 60, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488840</a>] [<a href="https://doi.org/10.1038/s41572-019-0109-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488840">Devuyst et al. (2019)</a> noted that the use of these confusing and inconsistent terms has hampered the detection and study of this renal disorder, which is genetically heterogeneous. These authors proposed the adoption of a unifying terminology, namely 'autosomal dominant tubulointerstitial kidney disease' (ADTKD), to refer to these diseases. The usual clinical manifestations of ADTKD in general are adult onset, progressive loss of kidney function, and variable proteinuria or microscopic hematuria. Renal biopsy shows interstitial fibrosis and tubular atrophy with a thickening and lamellation of tubular membranes, sometimes with secondary glomerulosclerosis. There may be microcystic tubular dilatations or renal cysts, but these findings are not pathognomonic. Although renal biopsy is important, <a href="#6" class="mim-tip-reference" title="Devuyst, O., Olinger, E., Weber, S., Eckardt, K.-U., Kmoch, S., Rampoldi, L., Bleyer, A. J. <strong>Autosomal dominant tubulointerstitial kidney disease.</strong> Nat. Rev. Dis. Primers. 5: 60, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488840</a>] [<a href="https://doi.org/10.1038/s41572-019-0109-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488840">Devuyst et al. (2019)</a> stated that it is not possible to make a diagnosis of ADTKD based solely on biopsy findings. Genetic testing using a candidate gene panel may be the most effective diagnostic method (see also <a href="#1" class="mim-tip-reference" title="Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R. <strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong> Am. J. Kidney Dis. 72: 411-418, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29784615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29784615</a>] [<a href="https://doi.org/10.1053/j.ajkd.2018.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29784615">Ayasreh et al., 2018</a>). Due to the nonspecific nature of the clinical and pathologic findings, ADTKD is likely underdiagnosed (summary by <a href="#20" class="mim-tip-reference" title="Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others. <strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong> Kidney Int. 98: 717-731, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32450155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32450155</a>] [<a href="https://doi.org/10.1016/j.kint.2020.04.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32450155">Olinger et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=32450155+31488840+29784615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Early Reports of Families With Unknown Mutations</em></strong></p><p>
|
|
<a href="#23" class="mim-tip-reference" title="Rosenbloom, F. M., Kelley, W. N., Carr, A. A., Seegmiller, J. E. <strong>Familial nephropathy and gout in a kindred. (Abstract)</strong> Clin. Res. 15: 270 only, 1967."None>Rosenbloom et al. (1967)</a> described a family in which multiple males in 3 generations died from renal failure at a relatively early age. All had hyperuricemia early in the course of the disease and developed gout. No distinctive histologic findings were yielded by renal biopsy. Transmission from father to son excluded X-linked inheritance. See <a href="#17" class="mim-tip-reference" title="McKusick, V. A. <strong>Familial nephropathy with gout.</strong> Birth Defects Orig. Art. Ser. X(4): 178-179, 1974."None>McKusick (1974)</a> for pedigree of the family of <a href="#23" class="mim-tip-reference" title="Rosenbloom, F. M., Kelley, W. N., Carr, A. A., Seegmiller, J. E. <strong>Familial nephropathy and gout in a kindred. (Abstract)</strong> Clin. Res. 15: 270 only, 1967."None>Rosenbloom et al. (1967)</a>. <a href="#7" class="mim-tip-reference" title="Duncan, H., Dixon, A. C. J. <strong>Gout, familial hyperuricemia, and renal disease.</strong> Quart. J. Med. 29: 127-135, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13818629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13818629</a>]" pmid="13818629">Duncan and Dixon (1960)</a>, <a href="#31" class="mim-tip-reference" title="Van Goor, W., Kooiker, C. J., Mees, F. J. D. <strong>An unusual form of renal disease associated with gout and hypertension.</strong> J. Clin. Path. 24: 354-359, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5556122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5556122</a>] [<a href="https://doi.org/10.1136/jcp.24.4.354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5556122">Van Goor et al. (1971)</a>, and <a href="#26" class="mim-tip-reference" title="Simmonds, H. A., Warren, D. J., Cameron, J. S., Potter, C. F., Farebrother, D. A. <strong>Familial gout and renal failure in young women.</strong> Clin. Nephrol. 14: 176-182, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7428192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7428192</a>]" pmid="7428192">Simmonds et al. (1980)</a> reported families with hyperuricemia and gout associated with renal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13818629+7428192+5556122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Leumann, E. <strong>Personal Communication.</strong> Zurich, Switzerland 1972."None>Leumann (1972)</a> and <a href="#12" class="mim-tip-reference" title="Leumann, E. P., Wegmann, W. <strong>Familial nephropathy with hyperuricemia and gout.</strong> Nephron 34: 51-57, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6855996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6855996</a>] [<a href="https://doi.org/10.1159/000182979" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6855996">Leumann and Wegmann (1983)</a> observed chronic interstitial nephropathy with disproportionate hyperuricemia in 2 girls and their mother. The mother suffered from gout beginning at age 20 years and required dialysis by age 34. The authors suggested that 'the severity of renal destruction by gout has been overestimated in the past and that families like the one described have been considered as gouty nephropathy.' <a href="#3" class="mim-tip-reference" title="Calabrese, G., Simmonds, H. A., Cameron, J. S., Davies, P. M. <strong>Precocious familial gout with reduced fractional urate clearance and normal purine enzymes.</strong> Quart. J. Med. 75: 441-450, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2388995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2388995</a>]" pmid="2388995">Calabrese et al. (1990)</a> and <a href="#4" class="mim-tip-reference" title="Cameron, J. S., Ogg, C. S., Moro, F., Chantler, C., Simmonds, H. A. <strong>Precocious familial gout. (Letter)</strong> Lancet 336: 745 only, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975911</a>] [<a href="https://doi.org/10.1016/0140-6736(90)92235-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1975911">Cameron et al. (1990)</a> reported further families. They emphasized the importance of investigating all sibs of such patients and of treatment with allopurinol of family members with a reduced fractional clearance of urate. Deterioration of renal function in patients who did not consistently take allopurinol and stability of renal function in compliers was the experience of <a href="#4" class="mim-tip-reference" title="Cameron, J. S., Ogg, C. S., Moro, F., Chantler, C., Simmonds, H. A. <strong>Precocious familial gout. (Letter)</strong> Lancet 336: 745 only, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975911</a>] [<a href="https://doi.org/10.1016/0140-6736(90)92235-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1975911">Cameron et al. (1990)</a> in 6 kindreds. <a href="#18" class="mim-tip-reference" title="Moro, F., Ogg, C. S., Simmonds, H. A., Cameron, J. S., Chantler, C., McBride, M. B., Duley, J. A., Davies, P. M. <strong>Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.</strong> Clin. Nephrol. 35: 263-269, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1873940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1873940</a>]" pmid="1873940">Moro et al. (1991)</a> found hyperuricemia associated with a grossly reduced fractional uric acid clearance in 2 children who did not yet have other signs of renal damage. They emphasized the usefulness of early recognition since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2388995+1975911+6855996+1873940" 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="#24" class="mim-tip-reference" title="Saeki, A., Hosoya, T., Okabe, H., Saji, M., Tabe, A., Ichida, K., Itoh, K., Joh, K., Sakai, O. <strong>Newly discovered familial juvenile gouty nephropathy in a Japanese family.</strong> Nephron 70: 359-366, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7477627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7477627</a>] [<a href="https://doi.org/10.1159/000188618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7477627">Saeki et al. (1995)</a> found autosomal dominant inheritance in a Japanese family. They reported on 2 sisters who had gout and renal insufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7477627" 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="#16" class="mim-tip-reference" title="McBride, M. B., Simmonds, H. A., Moro, F. <strong>Familial renal disease or familial juvenile hyperuricaemic nephropathy?</strong> J. Inherit. Metab. Dis. 20: 351-353, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266353</a>] [<a href="https://doi.org/10.1023/a:1005365625778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9266353">McBride et al. (1997)</a> stated that the Guy's Hospital group in London had identified 79 subjects with familial juvenile hyperuricemic nephropathy. They studied 36 children ranging in age from 3 to 17 years. Three were index cases. The other 33 were among 116 'healthy' relatives investigated from FJHN families in which the index case had presented initially with gout, renal disease, or both--generally with a strong family history spanning 2 or 3 generations (<a href="#18" class="mim-tip-reference" title="Moro, F., Ogg, C. S., Simmonds, H. A., Cameron, J. S., Chantler, C., McBride, M. B., Duley, J. A., Davies, P. M. <strong>Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.</strong> Clin. Nephrol. 35: 263-269, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1873940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1873940</a>]" pmid="1873940">Moro et al., 1991</a>). <a href="#16" class="mim-tip-reference" title="McBride, M. B., Simmonds, H. A., Moro, F. <strong>Familial renal disease or familial juvenile hyperuricaemic nephropathy?</strong> J. Inherit. Metab. Dis. 20: 351-353, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266353</a>] [<a href="https://doi.org/10.1023/a:1005365625778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9266353">McBride et al. (1997)</a> found a number of these children from kindreds who had hyperuricemia associated with a grossly reduced fractional uric acid clearance (FE(ur)) but normal renal function. (The FE(ur) is uric acid clearance factored by creatinine clearance x 100; mean for UK children = 18.4 +/- 5.1%.) The FE(ur) was 5.0 in affected children with normal or only mildly impaired renal function. These studies provided compelling evidence that hyperuricemia is a primary event in this type of nephropathy. The investigators underlined the importance of presymptomatic detection of the disorder, since in patients diagnosed before the onset of severe renal disease (creatinine clearance greater than 50 ml/min), allopurinol has ameliorated the hitherto rapid progression of the renal disease seen in earlier generations for up to 27 years (<a href="#19" class="mim-tip-reference" title="Moro, F., Simmonds, H. A., Cameron, J. S., Ogg, C. S., Williams, G. D., McBride, M. B., Davis, P. M. <strong>Does allopurinol affect the progression in familial juvenile gouty nephropathy?</strong> Adv. Exp. Med. Biol. 309A: 199-202, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1789208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1789208</a>] [<a href="https://doi.org/10.1007/978-1-4899-2638-8_45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1789208">Moro et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1789208+9266353+1873940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Families with Mutations in the UMOD Gene</em></strong></p><p>
|
|
<a href="#14" class="mim-tip-reference" title="Massari, P. U., Hsu, C. H., Barnes, R. V., Fox, I. H., Gikas, P. W., Weller, J. M. <strong>Familial hyperuricemia and renal disease.</strong> Arch. Intern. Med. 140: 680-684, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7396593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7396593</a>]" pmid="7396593">Massari et al. (1980)</a> described a family in which 9 individuals had renal disease characterized mainly by hyperuricemia. Three had gouty arthritis. Renal biopsy showed focal global and segmental sclerosis of glomeruli, occasional hypercellularity, foci of atrophic tubules, chronic interstitial inflammation, and folding and wrinkling of the glomerular basement membrane without electron-dense deposits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7396593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Hart, T. C., Gorry, M. C., Hart, P. S., Woodard, A. S., Shihabi, Z., Sandhu, J., Shirts, B., Xu, L., Zhu, H., Barmada, M. M., Bleyer, A. J. <strong>Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.</strong> J. Med. Genet. 39: 882-892, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471200</a>] [<a href="https://doi.org/10.1136/jmg.39.12.882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471200">Hart et al. (2002)</a> reported 4 unrelated families with a similar renal disease characterized by juvenile onset of hyperuricemia, polyuria, gout, and progressive renal insufficiency that was tubulointerstitial in origin. Family 4 had previously been reported by <a href="#14" class="mim-tip-reference" title="Massari, P. U., Hsu, C. H., Barnes, R. V., Fox, I. H., Gikas, P. W., Weller, J. M. <strong>Familial hyperuricemia and renal disease.</strong> Arch. Intern. Med. 140: 680-684, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7396593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7396593</a>]" pmid="7396593">Massari et al. (1980)</a>. In all patients, the disorder was associated with impaired urinary concentrating ability, which was postulated to result in a compensatory increase in proximal tubular reabsorption of uric acid and hyperuricemia. Renal biopsies showed tubular atrophy and interstitial fibrosis. Global glomerulosclerosis was also observed, although there was no evidence of glomerulonephritis. Necroscopy showed sheathing of the renal tubules by dense acellular hyaline fibrous tissue that likely represented abnormal deposition of the UMOD protein. Three families (families 1, 2, and 4) had a clinical diagnosis of familial juvenile hyperuricemic nephropathy (FJHN, HNFJ). Medullary cysts were present in 1 family (family 3), consistent with a clinical diagnosis of medullary cystic kidney disease (MCKD). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7396593+12471200" 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="Stiburkova, B., Majewski, J., Hodanova, K., Ondrova, L., Jerabkova, M., Zikanova, M., Vylet'al, P., Sebesta, I., Marinaki, A., Simmonds, A., Matthijs, G., Fryns, J.-P., Torres, R., Puig, J. G., Ott, J., Kmoch, S. <strong>Familial juvenile hyperuricaemic nephropathy (FJHN): linkage analysis in 15 families, physical and transcriptional characterisation of the FJHN critical region on chromosome 16p11.2 and the analysis of seven candidate genes.</strong> Europ. J. Hum. Genet. 11: 145-154, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12634862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12634862</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12634862">Stiburkova et al. (2003)</a> studied 3 Belgian brothers (family BE2) who reportedly developed the first symptoms of hyperuricemia and gouty arthritis after the age of 30 years; allopurinol treatment was started at that time. They had onset of renal failure between 45 and 50 years of age, with renal echography showing small hyperechogenic kidneys. Between 55 and 60 years of age, they developed arterial hypertension and progressive preterminal renal failure with elevated creatinine levels. Linkage analysis was consistent with linkage to chromosome 16p11. <a href="#32" class="mim-tip-reference" title="Vylet'al, P., Kublova, M., Kalbacova, M., Hodanova, K., Baresova, V., Stiburkova, B., Sikora, J., Hulkova, H., Zivny, J., Majewski, J., Simmonds, A., Fryns, J.-P., Venkat-Raman, G., Elleder, M., Kmoch, S. <strong>Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome.</strong> Kidney Int. 70: 1155-1169, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16883323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16883323</a>] [<a href="https://doi.org/10.1038/sj.ki.5001728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16883323">Vylet'al et al. (2006)</a> restudied family BE2 and reported that 2 of the 3 brothers had earlier onset of the disease at age 20 years. The eldest brother had undergone successful kidney transplantation at age 65 years, and the middle brother began hemodialysis at age 60 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12634862+16883323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Dahan, K., Devuyst, O., Smaers, M., Vertommen, D., Loute, G., Poux, J. M., Viron, B., Jacquot, C., Gagnadoux, M. F., Chauveau, D., Buchler, M., Cochat, P., Cosyns, J. P., Mougenot, B., Rider, M. H., Antignac, C., Verellen-Dumoulin, C., Pirson, Y. <strong>A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.</strong> J. Am. Soc. Nephrol. 14: 2883-2893, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14569098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14569098</a>] [<a href="https://doi.org/10.1097/01.asn.0000092147.83480.b5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14569098">Dahan et al. (2003)</a> reported 11 unrelated families with ADTKD1, 10 of which were of European descent and 1 of Moroccan descent. The 2 largest families had 11 and 7 affected individuals, respectively. At the time of examination, 17 patients had reached end-stage renal failure between ages 25 and 64 years, and 15 had chronic renal failure. Seven had preserved renal function, all of whom were younger than 34 years. Eighteen individuals had a history of gout with onset between 8 and 38 years. Renal biopsy, available from 6 individuals from 3 families, showed chronic interstitial nephritis with tubular atrophy and marked thickening of the tubular basement membrane. Renal imaging showed small cysts in 12 individuals with renal failure. Laboratory studies showed variably decreased urinary excretion of uromodulin compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14569098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V. <strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong> Am. J. Kidney Dis. 46: 52-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983957</a>] [<a href="https://doi.org/10.1053/j.ajkd.2005.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15983957">Lens et al. (2005)</a> reported 4 Spanish families with variable manifestations of ADTKD1, demonstrating the phenotypic heterogeneity of the disorder. Family 4 had previously been reported by <a href="#22" class="mim-tip-reference" title="Rezende-Lima, W., Parreira, K. S., Garcia-Gonzalez, M., Riveira, E., Banet, J. F., Lens, X. M. <strong>Homozygosity for uromodulin disorders: FJHN and MCKD-type 2.</strong> Kidney Int. 66: 558-563, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15253706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15253706</a>] [<a href="https://doi.org/10.1111/j.1523-1755.2004.00774.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15253706">Rezende-Lima et al. (2004)</a> as having medullary cystic kidney disease, although those authors noted that cyst formation may be a nonspecific secondary effect. There were 9 individuals in family 1 of <a href="#11" class="mim-tip-reference" title="Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V. <strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong> Am. J. Kidney Dis. 46: 52-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983957</a>] [<a href="https://doi.org/10.1053/j.ajkd.2005.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15983957">Lens et al. (2005)</a> who had highly variable clinical manifestations. Most had onset of hyperuricemia between 27 and 52 years of age, sometimes associated with gout. Four developed renal insufficiency between 29 and 57 years, but only 2 of these had end-stage renal disease after age 64. Four patients had arterial hypertension. Renal ultrasound showed medullary cysts in 2 patients with end-stage renal disease; renal biopsy in 1 of these patients showed chronic interstitial nephritis with marked thickening of tubular membranes. Other mutation carriers in the family did not have renal cysts. Two patients, ages 28 and 32, had only borderline increased serum uric acid without other manifestations. The findings suggested a clinical diagnosis of medullary cystic kidney disease. A 54-year-old man in family 2 had onset of hyperuricemia and gout at 15 and 31 years of age, respectively, and developed renal insufficiency at 44 years. Two older family members had end-stage renal disease at 51 and 67 years, respectively. Renal cysts were not present in this family; they were diagnosed with hyperuricemic nephropathy. Two sisters in family 3 had onset of hyperuricemia and renal insufficiency as teenagers. Renal biopsy showed dilatation of Bowman space in most glomeruli with rudimentary glomerular tufts without tubular dilatations; these findings were consistent with a diagnosis of glomerulocystic kidney disease. Their father and his sister developed end-stage renal disease at 55 and 62 years of age, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15253706+15983957" 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="Williams, S. E., Reed, A. A. C., Galvanovskis, J., Antignac, C., Goodship, T., Karet, F. E., Kotanko, P., Lhotta, K., Moriniere, V., Williams, P., Wong, W., Rorsman, P., Thakker, R. V. <strong>Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum.</strong> Hum. Molec. Genet. 18: 2963-2974, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19465746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19465746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19465746[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/10.1093/hmg/ddp235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19465746">Williams et al. (2009)</a> reported 6 unrelated probands (families 5, 6, 9, 11, 15, and 20), ranging from 14 to 72 years of age, with ADTKD1 confirmed by genetic analysis. Including affected family members, 13 individuals were identified. All patients had low fractional excretion of uric acid, with hyperuricemia in 73% and gout in 31%. Small or atrophic kidneys were found in 23% of patients, and cysts in 8%. About half had renal insufficiency, and 39% had end-stage renal failure. Two patients, including the 72-year-old, had a renal transplant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19465746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R. <strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong> Am. J. Kidney Dis. 72: 411-418, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29784615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29784615</a>] [<a href="https://doi.org/10.1053/j.ajkd.2018.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29784615">Ayasreh et al. (2018)</a> reported 9 unrelated Spanish families in which 44 individuals had ADTKD1 confirmed by genetic analysis. The majority of patients (87%) had hyperuricemia with a mean age at onset of 36.6 years. Other common features included gout (24%), hypertension (63%), polyuria/polydipsia (30%/24%), and proteinuria (10%). End-stage renal disease developed at an average age of 56 years. In 1 consanguineous family (F36), 2 members with a homozygous mutation developed end-stage renal disease at a mean age of 38.5 years, earlier than usual. Renal ultrasound showed small hyperechogenic kidneys in about 50% of those studied; cysts were found in 2 patients. Two patients had renal biopsies that showed tubular atrophy and interstitial fibrosis; 1 also had microcystic dilatation of the tubules. There was marked inter- and intrafamilial phenotypic variability, and the authors emphasized that neither hyperuricemia nor cysts represent hallmarks of the disease. Late onset of the disorder, incomplete penetrance, environmental factors, and other genetic or epigenetic changes may partially explain the variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29784615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others. <strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong> Kidney Int. 98: 717-731, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32450155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32450155</a>] [<a href="https://doi.org/10.1016/j.kint.2020.04.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32450155">Olinger et al. (2020)</a> identified 303 patients from 216 families with ADTKD1 confirmed by genetic analysis. The families were ascertained from 2 large cohorts from Europe and the United States comprising 726 patients from 585 families, and thus represented 38.4% of families. The mean age at presentation was 42 years (range 27-53); most patients had hyperuricemia and gout. End-stage kidney disease occurred at a mean age of 46 years (range 39-57). Regarding pathogenesis, the authors noted that abnormal accumulation of UMOD in the endoplasmic reticulum (ER) of the distal renal tubules may induce ER stress and disrupt function. Defective urinary concentration resulting in polyuria and polydipsia most likely results from impaired activity of the thick ascending loop of Henle, which causes plasma volume contraction with compensatory reabsorption activity of the proximal tubule, including upregulation of Na(+)-coupled urate transporters. This results in hyperuricemia that is unique to ADTKD1. <a href="#20" class="mim-tip-reference" title="Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others. <strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong> Kidney Int. 98: 717-731, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32450155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32450155</a>] [<a href="https://doi.org/10.1016/j.kint.2020.04.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32450155">Olinger et al. (2020)</a> provided a diagnostic algorithm based on simple scoring of clinical features, including urinary UMOD levels, hyperuricemia, and gout. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32450155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of ADTKD1 in the families reported by <a href="#11" class="mim-tip-reference" title="Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V. <strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong> Am. J. Kidney Dis. 46: 52-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983957</a>] [<a href="https://doi.org/10.1053/j.ajkd.2005.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15983957">Lens et al. (2005)</a> and <a href="#1" class="mim-tip-reference" title="Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R. <strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong> Am. J. Kidney Dis. 72: 411-418, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29784615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29784615</a>] [<a href="https://doi.org/10.1053/j.ajkd.2018.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29784615">Ayasreh et al. (2018)</a> was consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29784615+15983957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By genomewide linkage mapping in a 4-generation Italian pedigree with adult-onset renal disease, <a href="#25" class="mim-tip-reference" title="Scolari, F., Puzzer, D., Amoroso, A., Caridi, G., Ghiggeri, G. M., Maiorca, R., Aridon, P., De Fusco, M., Ballabio, A., Casari, G. <strong>Identification of a new locus for medullary cystic disease, on chromosome 16p12.</strong> Am. J. Hum. Genet. 64: 1655-1660, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10330352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10330352</a>] [<a href="https://doi.org/10.1086/302414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10330352">Scolari et al. (1999)</a> identified a disease locus, which they termed 'autosomal dominant medullary cystic disease-2' (MCKD2), on chromosome 16p12. The family fulfilled the typical diagnostic criteria of ADTKD1, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 showed a maximum 2-point lod score of 3.68, and the defined critical region spanned 10.5 cM, between D16S500 and SCNN1B1-2. <a href="#25" class="mim-tip-reference" title="Scolari, F., Puzzer, D., Amoroso, A., Caridi, G., Ghiggeri, G. M., Maiorca, R., Aridon, P., De Fusco, M., Ballabio, A., Casari, G. <strong>Identification of a new locus for medullary cystic disease, on chromosome 16p12.</strong> Am. J. Hum. Genet. 64: 1655-1660, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10330352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10330352</a>] [<a href="https://doi.org/10.1086/302414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10330352">Scolari et al. (1999)</a> noted that the UMOD gene, which maps to the critical region, is expressed mainly in the kidney, where it is localized to the epithelial cells of the thick ascending limb (TAL) of the Henle loop. Uromodulin has been functionally associated with the water nonpermeability of the TAL, a function that is altered in this disorder; UMOD was considered a candidate gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10330352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By linkage analysis of 2 families with ADTKD, <a href="#9" class="mim-tip-reference" title="Hart, T. C., Gorry, M. C., Hart, P. S., Woodard, A. S., Shihabi, Z., Sandhu, J., Shirts, B., Xu, L., Zhu, H., Barmada, M. M., Bleyer, A. J. <strong>Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.</strong> J. Med. Genet. 39: 882-892, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471200</a>] [<a href="https://doi.org/10.1136/jmg.39.12.882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471200">Hart et al. (2002)</a> identified a candidate region between 16p13.11 (D16S499) and 16p12.2 (D16S403). The authors noted that this region did not overlap with a region on 16p12 identified by <a href="#10" class="mim-tip-reference" title="Kamatani, N., Moritani, M., Yamanaka, H., Takeuchi, F., Hosoya, T., Itakura, M. <strong>Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.</strong> Arthritis Rheum. 43: 925-929, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10765940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10765940</a>] [<a href="https://doi.org/10.1002/1529-0131(200004)43:4<925::AID-ANR26>3.0.CO;2-B" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10765940">Kamatani et al. (2000)</a> in a large Japanese family (see below). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10765940+12471200" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Stacey, J. M., Turner, J. J. O., Harding, B., Nesbit, M. A., Kotanko, P., Lhotta, K., Puig, J. G., Torres, R. J., Thakker, R. V. <strong>Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13.</strong> J. Clin. Endocr. Metab. 88: 464-470, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519891</a>] [<a href="https://doi.org/10.1210/jc.2002-021268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12519891">Stacey et al. (2003)</a> pursued linkage studies in 7 European families with ADTKD and used 11 chromosome 16p13-p11 polymorphic loci. Cosegregation between these polymorphic loci and the disorder was observed in 5 of the families; linkage was established between ADTKD and 6 loci. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12519891" 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="Vylet'al, P., Kublova, M., Kalbacova, M., Hodanova, K., Baresova, V., Stiburkova, B., Sikora, J., Hulkova, H., Zivny, J., Majewski, J., Simmonds, A., Fryns, J.-P., Venkat-Raman, G., Elleder, M., Kmoch, S. <strong>Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome.</strong> Kidney Int. 70: 1155-1169, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16883323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16883323</a>] [<a href="https://doi.org/10.1038/sj.ki.5001728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16883323">Vylet'al et al. (2006)</a> performed linkage analysis in 19 families with variable manifestations of ADTKD and found linkage to chromosome 16p11.2 in 9 of the families. Quantitative analysis showed that UMOD excretion was significantly reduced in almost all affected individuals, regardless of which linkage group they belonged to; 1 family (CZ3), which did not link to any known loci, showed normal UMOD excretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16883323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity</em></strong></p><p>
|
|
<a href="#34" class="mim-tip-reference" title="Yokota, N., Yamanaka, H., Yamamoto, Y., Fujimoto, S., Eto, T., Tanaka, K. <strong>Autosomal dominant transmission of gouty arthritis with renal disease in a large Japanese family.</strong> Ann. Rheum. Dis. 50: 108-111, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847794</a>] [<a href="https://doi.org/10.1136/ard.50.2.108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1847794">Yokota et al. (1991)</a> described a large Japanese family with autosomal dominant transmission of gouty arthritis with renal disease. At least 20 members of the family were affected. <a href="#10" class="mim-tip-reference" title="Kamatani, N., Moritani, M., Yamanaka, H., Takeuchi, F., Hosoya, T., Itakura, M. <strong>Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.</strong> Arthritis Rheum. 43: 925-929, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10765940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10765940</a>] [<a href="https://doi.org/10.1002/1529-0131(200004)43:4<925::AID-ANR26>3.0.CO;2-B" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10765940">Kamatani et al. (2000)</a> obtained DNA from 13 affected and 18 unaffected members. A genomewide search initially showed evidence of linkage for a marker on 16p. Subsequently, the same subjects were genotyped for 12 additional markers spanning approximately 30 cM on the short arm of chromosome 16. They obtained a maximum 2-point lod score of 6.04 at theta = 0.0 with the marker D16S401; multipoint linkage analysis yielded a maximum lod score of 6.14 with markers D16S401 and D16S3113, and established a minimum candidate interval of approximately 9 cM in the 16p12 region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1847794+10765940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Stacey, J. M., Turner, J. J. O., Harding, B., Nesbit, M. A., Kotanko, P., Lhotta, K., Puig, J. G., Torres, R. J., Thakker, R. V. <strong>Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13.</strong> J. Clin. Endocr. Metab. 88: 464-470, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519891</a>] [<a href="https://doi.org/10.1210/jc.2002-021268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12519891">Stacey et al. (2003)</a> excluded linkage to chromosome 16p13-p11 in 2 European families with ADTKD, thereby demonstrating genetic heterogeneity (see <a href="/entry/614227">614227</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12519891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 4 unrelated families with ADTKD1, <a href="#9" class="mim-tip-reference" title="Hart, T. C., Gorry, M. C., Hart, P. S., Woodard, A. S., Shihabi, Z., Sandhu, J., Shirts, B., Xu, L., Zhu, H., Barmada, M. M., Bleyer, A. J. <strong>Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.</strong> J. Med. Genet. 39: 882-892, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471200</a>] [<a href="https://doi.org/10.1136/jmg.39.12.882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471200">Hart et al. (2002)</a> identified 4 different heterozygous mutations in exon 4 of the UMOD gene (<a href="/entry/191845#0001">191845.0001</a>-<a href="/entry/191845#0004">191845.0004</a>). The mutations, which were found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the families. Three families (families 1, 2, and 4) had a clinical diagnosis of familial juvenile hyperuricemic nephropathy (FJHN, HNFJ), whereas family 3 was diagnosed clinically with medullary cystic kidney disease (MCKD). Family 4 had previously been reported by <a href="#14" class="mim-tip-reference" title="Massari, P. U., Hsu, C. H., Barnes, R. V., Fox, I. H., Gikas, P. W., Weller, J. M. <strong>Familial hyperuricemia and renal disease.</strong> Arch. Intern. Med. 140: 680-684, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7396593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7396593</a>]" pmid="7396593">Massari et al. (1980)</a>. Functional studies of the variants and studies of patient cells were not performed, but the authors postulated that the mutations caused tertiary structural changes in the uromodulin protein that could alter cytokine binding and ultimately lead to fibrosis and progressive renal failure. The report established that the clinical entities of FJHN and MCKD not only share clinical features, but are also either allelic or variable manifestations of the same disease. Noting that hyperuricemia and medullary cysts are variable features and that the conditions result from mutations in the same gene, the authors suggested the designation 'uromodulin-associated kidney disease.' <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7396593+12471200" 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 5 unrelated kindreds with ADTKD1, 2 from Austria and 3 from Spain, <a href="#30" class="mim-tip-reference" title="Turner, J. J. O., Stacey, J. M., Harding, B., Kotanko, P., Lhotta, K., Puig, J. G., Roberts, I., Torres, R. J., Thakker, R. V. <strong>UROMODULIN mutations cause familial juvenile hyperuricemic nephropathy.</strong> J. Clin. Endocr. Metab. 88: 1398-1401, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629136</a>] [<a href="https://doi.org/10.1210/jc.2002-021973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629136">Turner et al. (2003)</a> identified 5 heterozygous missense mutations in the UMOD gene (<a href="/entry/191845#0005">191845.0005</a>-<a href="/entry/191845#0009">191845.0009</a>) that altered evolutionary conserved residues. These mutations were not found in 110 alleles from 55 unrelated normal individuals. Functional studies of the variants were not performed, but the authors postulated a loss-of-function effect. The families had previously been reported by <a href="#27" class="mim-tip-reference" title="Stacey, J. M., Turner, J. J. O., Harding, B., Nesbit, M. A., Kotanko, P., Lhotta, K., Puig, J. G., Torres, R. J., Thakker, R. V. <strong>Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13.</strong> J. Clin. Endocr. Metab. 88: 464-470, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519891</a>] [<a href="https://doi.org/10.1210/jc.2002-021268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12519891">Stacey et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12519891+12629136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 4 unrelated Italian families with variable manifestations of ADTKD1, <a href="#21" class="mim-tip-reference" title="Rampoldi, L., Caridi, G., Santon, D., Boaretto, F., Bernascone, I., Lamorte, G., Tardanico, R., Dagnino, M., Colussi, G., Scolari, F., Ghiggeri, G. M., Amoroso, A., Casari, G. <strong>Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics.</strong> Hum. Molec. Genet. 12: 3369-3384, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570709</a>] [<a href="https://doi.org/10.1093/hmg/ddg353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570709">Rampoldi et al. (2003)</a> identified heterozygous missense mutations in the UMOD gene (see, e.g., C315R, <a href="/entry/191845#0010">191845.0010</a> and C148W, <a href="/entry/191845#0015">191845.0015</a>). All mutations affected highly conserved cysteine residues and were predicted to affect protein structure. Immunohistochemistry of kidney biopsies revealed dense intracellular accumulation of uromodulin in tubular epithelia of the thick ascending limb of Henle loop. Electron microscopy showed accumulation of dense fibrillar material within the endoplasmic reticulum, and patient urine samples consistently showed a severe reduction of excreted uromodulin. Experiments in transfected cells showed that all 4 mutations caused a delay in protein export to the plasma membrane due to a longer retention time in the ER. The protein maturation impairment and retention in the ER, which may trigger ubiquitination, suggested a pathogenetic mechanism leading to these kidney diseases. <a href="#21" class="mim-tip-reference" title="Rampoldi, L., Caridi, G., Santon, D., Boaretto, F., Bernascone, I., Lamorte, G., Tardanico, R., Dagnino, M., Colussi, G., Scolari, F., Ghiggeri, G. M., Amoroso, A., Casari, G. <strong>Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics.</strong> Hum. Molec. Genet. 12: 3369-3384, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570709</a>] [<a href="https://doi.org/10.1093/hmg/ddg353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570709">Rampoldi et al. (2003)</a> postulated that hyperuricemia is a secondary effect of volume contraction resulting from UMOD dysfunction in the thick ascending loop of Henle. Three families had a clinical diagnosis of MCKD/FJHN (including a family previously reported by <a href="#25" class="mim-tip-reference" title="Scolari, F., Puzzer, D., Amoroso, A., Caridi, G., Ghiggeri, G. M., Maiorca, R., Aridon, P., De Fusco, M., Ballabio, A., Casari, G. <strong>Identification of a new locus for medullary cystic disease, on chromosome 16p12.</strong> Am. J. Hum. Genet. 64: 1655-1660, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10330352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10330352</a>] [<a href="https://doi.org/10.1086/302414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10330352">Scolari et al., 1999</a>), and 1 family had a clinical diagnosis of glomerulocystic kidney disease (GCKD), thus demonstrating that these clinical entities are allelic and likely are different manifestations of the same disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10330352+14570709" 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 patients from 11 families with ADTKD1, <a href="#5" class="mim-tip-reference" title="Dahan, K., Devuyst, O., Smaers, M., Vertommen, D., Loute, G., Poux, J. M., Viron, B., Jacquot, C., Gagnadoux, M. F., Chauveau, D., Buchler, M., Cochat, P., Cosyns, J. P., Mougenot, B., Rider, M. H., Antignac, C., Verellen-Dumoulin, C., Pirson, Y. <strong>A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.</strong> J. Am. Soc. Nephrol. 14: 2883-2893, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14569098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14569098</a>] [<a href="https://doi.org/10.1097/01.asn.0000092147.83480.b5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14569098">Dahan et al. (2003)</a> identified 11 different heterozygous mutations in the UMOD gene, including 10 novel mutations (see, e.g., <a href="/entry/191845#0012">191845.0012</a>). There were 10 missense mutations and 1 in-frame deletion. All of the mutations occurred at highly conserved residues in exon 4, and 5 of the mutations affected a conserved cysteine residue. The families were ascertained from a larger group of 25 families with a similar phenotype; thus, UMOD mutations were found in 44% of families. Medullary cysts were identified in 9 patients from 8 families. Patient kidney samples showed abnormal uromodulin immunostaining within enlarged or cystic profiles in tubules in the thick ascending loop, and not at the apical membrane as observed in controls. Mutant UMOD was not found in proximal tubules. Patients also showed decreased urinary excretion of wildtype uromodulin. These findings indicated that mutant uromodulin accumulates within renal tubular cells in patients with UMOD mutations. <a href="#5" class="mim-tip-reference" title="Dahan, K., Devuyst, O., Smaers, M., Vertommen, D., Loute, G., Poux, J. M., Viron, B., Jacquot, C., Gagnadoux, M. F., Chauveau, D., Buchler, M., Cochat, P., Cosyns, J. P., Mougenot, B., Rider, M. H., Antignac, C., Verellen-Dumoulin, C., Pirson, Y. <strong>A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.</strong> J. Am. Soc. Nephrol. 14: 2883-2893, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14569098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14569098</a>] [<a href="https://doi.org/10.1097/01.asn.0000092147.83480.b5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14569098">Dahan et al. (2003)</a> concluded that the clinical diagnoses of FJHN and MCKD2 represent 2 facets of the same disease entity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14569098" 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 14 affected members of a large consanguineous Spanish family with ADTKD1, <a href="#22" class="mim-tip-reference" title="Rezende-Lima, W., Parreira, K. S., Garcia-Gonzalez, M., Riveira, E., Banet, J. F., Lens, X. M. <strong>Homozygosity for uromodulin disorders: FJHN and MCKD-type 2.</strong> Kidney Int. 66: 558-563, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15253706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15253706</a>] [<a href="https://doi.org/10.1111/j.1523-1755.2004.00774.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15253706">Rezende-Lima et al. (2004)</a> identified a C255Y mutation in the UMOD gene (<a href="/entry/191845#0008">191845.0008</a>). Eleven family members were heterozygous for the mutation, whereas 3 were homozygous. The homozygous individuals had earlier disease onset than the heterozygous carriers, but the report demonstrated that homozygosity for UMOD mutations is not lethal. The clinical phenotype was consistent with medullary cystic kidney disease (MCKD), although the authors noted that cyst formation may be a nonspecific secondary effect. This family was also reported as family F4 by <a href="#11" class="mim-tip-reference" title="Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V. <strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong> Am. J. Kidney Dis. 46: 52-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983957</a>] [<a href="https://doi.org/10.1053/j.ajkd.2005.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15983957">Lens et al. (2005)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15253706+15983957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 apparently unrelated Spanish families with ADTKD1, <a href="#11" class="mim-tip-reference" title="Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V. <strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong> Am. J. Kidney Dis. 46: 52-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983957</a>] [<a href="https://doi.org/10.1053/j.ajkd.2005.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15983957">Lens et al. (2005)</a> identified the same heterozygous missense mutation in the UMOD gene (Q316P; <a href="/entry/191845#0014">191845.0014</a>). The mutation segregated with the phenotype in the families and was not found in 100 control chromosomes. Family 1 had a clinical phenotype consistent with MCKD, and family 2 had a clinical phenotype consistent with FJHN. The demonstration of the same mutation in both families further supported that MCKD and FJHN are the same disease entity. A third Spanish family (family 3), with a clinical phenotype consistent with GCKD, carried a different heterozygous missense mutation (C300G; <a href="/entry/191845#0009">191845.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15983957" 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="Vylet'al, P., Kublova, M., Kalbacova, M., Hodanova, K., Baresova, V., Stiburkova, B., Sikora, J., Hulkova, H., Zivny, J., Majewski, J., Simmonds, A., Fryns, J.-P., Venkat-Raman, G., Elleder, M., Kmoch, S. <strong>Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome.</strong> Kidney Int. 70: 1155-1169, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16883323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16883323</a>] [<a href="https://doi.org/10.1038/sj.ki.5001728" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16883323">Vylet'al et al. (2006)</a> sequenced the UMOD gene in 19 families with variable manifestations of ADTKD1 and identified heterozygous mutations in 6 families, 5 of which had been previously reported (kindred 6 from <a href="#15" class="mim-tip-reference" title="McBride, M. B., Rigden, S., Haycock, G. B., Dalton, N., Van't Hoff, W., Rees, L., Venkat-Raman, G. V., Moro, F., Ogg, C. S., Cameron, J. S., Simmonds, H. A. <strong>Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children.</strong> Pediat. Nephrol. 12: 357-364, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686952</a>] [<a href="https://doi.org/10.1007/s004670050466" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9686952">McBride et al., 1998</a>; kindreds A and B from <a href="#29" class="mim-tip-reference" title="Stiburkova, B., Majewski, J., Sebesta, I., Zhang, W., Ott, J., Kmoch, S. <strong>Familial juvenile hyperuricemic nephropathy: localization of the gene on chromosome 16p11.2--and evidence for genetic heterogeneity.</strong> Am. J. Hum. Genet. 66: 1989-1994, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780922</a>] [<a href="https://doi.org/10.1086/302936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10780922">Stiburkova et al., 2000</a>; <a href="#8" class="mim-tip-reference" title="Fairbanks, L. D., Cameron, J. S., Venkat-Raman, G., Rigden, S. P. A., Rees, L., Van't Hoff, W., Mansell, M., Pattison, J., Goldsmith, D. J. A., Simmonds, H. A. <strong>Early treatment with allopurinol in familial juvenile hyperuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.</strong> Quart. J. Med. 95: 597-607, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205338</a>] [<a href="https://doi.org/10.1093/qjmed/95.9.597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205338">Fairbanks et al., 2002</a>; and family BE2 from <a href="#28" class="mim-tip-reference" title="Stiburkova, B., Majewski, J., Hodanova, K., Ondrova, L., Jerabkova, M., Zikanova, M., Vylet'al, P., Sebesta, I., Marinaki, A., Simmonds, A., Matthijs, G., Fryns, J.-P., Torres, R., Puig, J. G., Ott, J., Kmoch, S. <strong>Familial juvenile hyperuricaemic nephropathy (FJHN): linkage analysis in 15 families, physical and transcriptional characterisation of the FJHN critical region on chromosome 16p11.2 and the analysis of seven candidate genes.</strong> Europ. J. Hum. Genet. 11: 145-154, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12634862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12634862</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12634862">Stiburkova et al., 2003</a>) (see, e.g., <a href="/entry/191845#0006">191845.0006</a> and <a href="/entry/191845#0011">191845.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16883323+9686952+12634862+10780922+12205338" 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 6 of 17 probands with ADTKD who were studied for UMOD mutations, <a href="#33" class="mim-tip-reference" title="Williams, S. E., Reed, A. A. C., Galvanovskis, J., Antignac, C., Goodship, T., Karet, F. E., Kotanko, P., Lhotta, K., Moriniere, V., Williams, P., Wong, W., Rorsman, P., Thakker, R. V. <strong>Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum.</strong> Hum. Molec. Genet. 18: 2963-2974, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19465746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19465746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19465746[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/10.1093/hmg/ddp235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19465746">Williams et al. (2009)</a> identified 6 different heterozygous missense mutations in the UMOD gene (see, e.g., D196N, <a href="/entry/191845#0016">191845.0016</a>). In vitro functional studies of some of the mutations expressed in HeLa cells showed that the mutant uromodulins had significantly delayed maturation compared to wildtype, with abnormal protein retention in the ER and reduced or absent expression at the plasma membrane. There were different effects allowing the identification of 2 mutation groups: group A (including mutants C32W, D196N, and G488R) had 50% maturation compared to wildtype with some expression at the plasma membrane, whereas group B (including mutants C126R, <a href="/entry/191845#0006">191845.0006</a>; N128S, <a href="/entry/191845#0007">191845.0007</a>; and C223R) had 25% maturation compared to wildtype and absence of expression at the plasma membrane. There were no phenotypic differences between patients with group A and group B mutations. The findings suggested that abnormal folding of the mutant proteins resulted in protein retention in the ER, which may trigger apoptosis and underlie the mechanism for disease pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19465746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 10 unrelated families with ADTKD1, <a href="#35" class="mim-tip-reference" title="Zaucke, F., Boehnlein, J. M., Steffens, S., Polishchuk, R. S., Rampoldi, L., Fischer, A., Pasch, A., Boehm, C. W. A., Baasner, A., Attanasio, M., Hoppe, B., Hopfer, H., Beck, B. B., Sayer, J. A., Hildebrandt, F., Wolf, M. T. F. <strong>Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression.</strong> Hum. Molec. Genet. 19: 1985-1997, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20172860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20172860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20172860[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/10.1093/hmg/ddq077" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20172860">Zaucke et al. (2010)</a> identified 7 novel and 3 previously reported heterozygous missense mutations in the UMOD gene (see, e.g., <a href="/entry/191845#0009">191845.0009</a> and <a href="/entry/191845#0013">191845.0013</a>). Most of the mutations affected conserved cysteine residues. The number of UMOD-positive primary cilia in renal biopsy samples from 2 of the patients was significantly decreased compared to control samples. The authors suggested that this defect may contribute to cyst formation. The families were ascertained from a cohort of 44 families with nephropathy from western Europe and the United States who underwent direct sequencing of the UMOD gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20172860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others. <strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong> Kidney Int. 98: 717-731, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32450155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32450155</a>] [<a href="https://doi.org/10.1016/j.kint.2020.04.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32450155">Olinger et al. (2020)</a> identified 106 unique heterozygous mutations in the UMOD gene in 303 patients from 216 families with ADTKD1. The families were ascertained from 2 large cohorts from Europe and the United States comprising 726 patients from 585 families, and thus represented 38.4% of families. The majority (95.3%) of the mutations were missense, and most occurred in exon 3. About half involved cysteine bonds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32450155" 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 review article on the pathogenesis of ADTKD1, <a href="#6" class="mim-tip-reference" title="Devuyst, O., Olinger, E., Weber, S., Eckardt, K.-U., Kmoch, S., Rampoldi, L., Bleyer, A. J. <strong>Autosomal dominant tubulointerstitial kidney disease.</strong> Nat. Rev. Dis. Primers. 5: 60, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488840</a>] [<a href="https://doi.org/10.1038/s41572-019-0109-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488840">Devuyst et al. (2019)</a> concluded that the disorder results from a toxic gain-of-function effect due to abnormal accumulation of mutant UMOD in the ER, where it is believed to stimulate the unfolded protein response and activate pathways of ER stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31488840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In a genetic study of 56 Spanish families with a clinical diagnosis of ADTKD, <a href="#1" class="mim-tip-reference" title="Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R. <strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong> Am. J. Kidney Dis. 72: 411-418, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29784615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29784615</a>] [<a href="https://doi.org/10.1053/j.ajkd.2018.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29784615">Ayasreh et al. (2018)</a> found that 25 (45%) carried pathogenic mutations in either the UMOD gene (9 families, 36%) or MUC1 gene (16 families, 64%). These findings suggested that MUC1 mutations are the most common cause of the disorder in that population. No pathogenic mutations were identified in REN (<a href="/entry/179820">179820</a>) or HNF1B (<a href="/entry/189907">189907</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29784615" 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 genetic study of 2 large cohorts from Europe and the United States comprising 726 patients from 585 families with ADTKD, <a href="#20" class="mim-tip-reference" title="Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others. <strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong> Kidney Int. 98: 717-731, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32450155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32450155</a>] [<a href="https://doi.org/10.1016/j.kint.2020.04.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32450155">Olinger et al. (2020)</a> found that 303 patients from 216 families (38.4%) had mutations in the UMOD gene. MUC1 mutations were found in 104 patients from 93 families (21%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32450155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Bernascone, I., Janas, S., Ikehata, M., Trudu, M., Corbelli, A., Schaeffer, C., Rastaldi, M. P., Devuyst, O., Rampoldi, L. <strong>A transgenic mouse model for uromodulin-associated kidney diseases shows specific tubulo-interstitial damage, urinary concentrating defect and renal failure.</strong> Hum. Molec. Genet. 19: 2998-3010, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20472742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20472742</a>] [<a href="https://doi.org/10.1093/hmg/ddq205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20472742">Bernascone et al. (2010)</a> generated a transgenic mouse model for the UMOD-associated kidney diseases HNFJ and MCKD. The transgenic mice, which had a Umod C147W mutation corresponding to the human UMOD C148W mutation (<a href="/entry/191845#0015">191845.0015</a>), recapitulated most of the features observed in patients with UMOD kidney disease, with urinary concentrating defect of renal origin and progressive renal injury, i.e., tubulointerstitial fibrosis with inflammatory cell infiltration, tubule dilation, and specific damage of the thick ascending limb of the loop of Henle (TAL), leading to mild renal failure. As observed in patients with the C148W mutation, the mutant mice showed a marked reduction in urinary uromodulin excretion. Mutant uromodulin was retained in the endoplasmic reticulum (ER) of expressing cells, leading to ER hyperplasia. The authors suggested that impaired TAL function is a consequence of a gain-of-function effect of UMOD mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20472742" 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="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="Ayasreh2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R.
|
|
<strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong>
|
|
Am. J. Kidney Dis. 72: 411-418, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29784615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29784615</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29784615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1053/j.ajkd.2018.03.019" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bernascone2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernascone, I., Janas, S., Ikehata, M., Trudu, M., Corbelli, A., Schaeffer, C., Rastaldi, M. P., Devuyst, O., Rampoldi, L.
|
|
<strong>A transgenic mouse model for uromodulin-associated kidney diseases shows specific tubulo-interstitial damage, urinary concentrating defect and renal failure.</strong>
|
|
Hum. Molec. Genet. 19: 2998-3010, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20472742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20472742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20472742" 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/ddq205" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Calabrese1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Calabrese, G., Simmonds, H. A., Cameron, J. S., Davies, P. M.
|
|
<strong>Precocious familial gout with reduced fractional urate clearance and normal purine enzymes.</strong>
|
|
Quart. J. Med. 75: 441-450, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2388995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2388995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2388995" 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="4" class="mim-anchor"></a>
|
|
<a id="Cameron1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cameron, J. S., Ogg, C. S., Moro, F., Chantler, C., Simmonds, H. A.
|
|
<strong>Precocious familial gout. (Letter)</strong>
|
|
Lancet 336: 745 only, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1975911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0140-6736(90)92235-a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dahan2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dahan, K., Devuyst, O., Smaers, M., Vertommen, D., Loute, G., Poux, J. M., Viron, B., Jacquot, C., Gagnadoux, M. F., Chauveau, D., Buchler, M., Cochat, P., Cosyns, J. P., Mougenot, B., Rider, M. H., Antignac, C., Verellen-Dumoulin, C., Pirson, Y.
|
|
<strong>A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.</strong>
|
|
J. Am. Soc. Nephrol. 14: 2883-2893, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14569098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14569098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14569098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/01.asn.0000092147.83480.b5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Devuyst2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Devuyst, O., Olinger, E., Weber, S., Eckardt, K.-U., Kmoch, S., Rampoldi, L., Bleyer, A. J.
|
|
<strong>Autosomal dominant tubulointerstitial kidney disease.</strong>
|
|
Nat. Rev. Dis. Primers. 5: 60, 2019. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31488840" 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/s41572-019-0109-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Duncan1960" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Duncan, H., Dixon, A. C. J.
|
|
<strong>Gout, familial hyperuricemia, and renal disease.</strong>
|
|
Quart. J. Med. 29: 127-135, 1960.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13818629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13818629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13818629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Fairbanks2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fairbanks, L. D., Cameron, J. S., Venkat-Raman, G., Rigden, S. P. A., Rees, L., Van't Hoff, W., Mansell, M., Pattison, J., Goldsmith, D. J. A., Simmonds, H. A.
|
|
<strong>Early treatment with allopurinol in familial juvenile hyperuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.</strong>
|
|
Quart. J. Med. 95: 597-607, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205338</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205338" 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/qjmed/95.9.597" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Hart2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hart, T. C., Gorry, M. C., Hart, P. S., Woodard, A. S., Shihabi, Z., Sandhu, J., Shirts, B., Xu, L., Zhu, H., Barmada, M. M., Bleyer, A. J.
|
|
<strong>Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.</strong>
|
|
J. Med. Genet. 39: 882-892, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471200</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12471200" 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.39.12.882" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kamatani2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kamatani, N., Moritani, M., Yamanaka, H., Takeuchi, F., Hosoya, T., Itakura, M.
|
|
<strong>Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.</strong>
|
|
Arthritis Rheum. 43: 925-929, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10765940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10765940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10765940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1529-0131(200004)43:4<925::AID-ANR26>3.0.CO;2-B" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Lens2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V.
|
|
<strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong>
|
|
Am. J. Kidney Dis. 46: 52-57, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15983957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1053/j.ajkd.2005.04.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Leumann1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leumann, E. P., Wegmann, W.
|
|
<strong>Familial nephropathy with hyperuricemia and gout.</strong>
|
|
Nephron 34: 51-57, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6855996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6855996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6855996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000182979" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Leumann1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leumann, E.
|
|
<strong>Personal Communication.</strong>
|
|
Zurich, Switzerland 1972.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Massari1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Massari, P. U., Hsu, C. H., Barnes, R. V., Fox, I. H., Gikas, P. W., Weller, J. M.
|
|
<strong>Familial hyperuricemia and renal disease.</strong>
|
|
Arch. Intern. Med. 140: 680-684, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7396593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7396593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7396593" 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="15" class="mim-anchor"></a>
|
|
<a id="McBride1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McBride, M. B., Rigden, S., Haycock, G. B., Dalton, N., Van't Hoff, W., Rees, L., Venkat-Raman, G. V., Moro, F., Ogg, C. S., Cameron, J. S., Simmonds, H. A.
|
|
<strong>Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children.</strong>
|
|
Pediat. Nephrol. 12: 357-364, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9686952" 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/s004670050466" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="McBride1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McBride, M. B., Simmonds, H. A., Moro, F.
|
|
<strong>Familial renal disease or familial juvenile hyperuricaemic nephropathy?</strong>
|
|
J. Inherit. Metab. Dis. 20: 351-353, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1023/a:1005365625778" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="McKusick1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A.
|
|
<strong>Familial nephropathy with gout.</strong>
|
|
Birth Defects Orig. Art. Ser. X(4): 178-179, 1974.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Moro1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moro, F., Ogg, C. S., Simmonds, H. A., Cameron, J. S., Chantler, C., McBride, M. B., Duley, J. A., Davies, P. M.
|
|
<strong>Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.</strong>
|
|
Clin. Nephrol. 35: 263-269, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1873940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1873940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1873940" 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="19" class="mim-anchor"></a>
|
|
<a id="Moro1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moro, F., Simmonds, H. A., Cameron, J. S., Ogg, C. S., Williams, G. D., McBride, M. B., Davis, P. M.
|
|
<strong>Does allopurinol affect the progression in familial juvenile gouty nephropathy?</strong>
|
|
Adv. Exp. Med. Biol. 309A: 199-202, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1789208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1789208</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1789208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/978-1-4899-2638-8_45" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Olinger2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others.
|
|
<strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong>
|
|
Kidney Int. 98: 717-731, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32450155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32450155</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32450155" 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.kint.2020.04.038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Rampoldi2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rampoldi, L., Caridi, G., Santon, D., Boaretto, F., Bernascone, I., Lamorte, G., Tardanico, R., Dagnino, M., Colussi, G., Scolari, F., Ghiggeri, G. M., Amoroso, A., Casari, G.
|
|
<strong>Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics.</strong>
|
|
Hum. Molec. Genet. 12: 3369-3384, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570709" 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/ddg353" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Rezende-Lima2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rezende-Lima, W., Parreira, K. S., Garcia-Gonzalez, M., Riveira, E., Banet, J. F., Lens, X. M.
|
|
<strong>Homozygosity for uromodulin disorders: FJHN and MCKD-type 2.</strong>
|
|
Kidney Int. 66: 558-563, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15253706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15253706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15253706" 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.1523-1755.2004.00774.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Rosenbloom1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenbloom, F. M., Kelley, W. N., Carr, A. A., Seegmiller, J. E.
|
|
<strong>Familial nephropathy and gout in a kindred. (Abstract)</strong>
|
|
Clin. Res. 15: 270 only, 1967.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Saeki1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saeki, A., Hosoya, T., Okabe, H., Saji, M., Tabe, A., Ichida, K., Itoh, K., Joh, K., Sakai, O.
|
|
<strong>Newly discovered familial juvenile gouty nephropathy in a Japanese family.</strong>
|
|
Nephron 70: 359-366, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7477627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7477627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7477627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000188618" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Scolari1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scolari, F., Puzzer, D., Amoroso, A., Caridi, G., Ghiggeri, G. M., Maiorca, R., Aridon, P., De Fusco, M., Ballabio, A., Casari, G.
|
|
<strong>Identification of a new locus for medullary cystic disease, on chromosome 16p12.</strong>
|
|
Am. J. Hum. Genet. 64: 1655-1660, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10330352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10330352</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10330352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302414" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Simmonds1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Simmonds, H. A., Warren, D. J., Cameron, J. S., Potter, C. F., Farebrother, D. A.
|
|
<strong>Familial gout and renal failure in young women.</strong>
|
|
Clin. Nephrol. 14: 176-182, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7428192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7428192</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7428192" 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="27" class="mim-anchor"></a>
|
|
<a id="Stacey2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stacey, J. M., Turner, J. J. O., Harding, B., Nesbit, M. A., Kotanko, P., Lhotta, K., Puig, J. G., Torres, R. J., Thakker, R. V.
|
|
<strong>Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13.</strong>
|
|
J. Clin. Endocr. Metab. 88: 464-470, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519891</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12519891" 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.2002-021268" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Stiburkova2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stiburkova, B., Majewski, J., Hodanova, K., Ondrova, L., Jerabkova, M., Zikanova, M., Vylet'al, P., Sebesta, I., Marinaki, A., Simmonds, A., Matthijs, G., Fryns, J.-P., Torres, R., Puig, J. G., Ott, J., Kmoch, S.
|
|
<strong>Familial juvenile hyperuricaemic nephropathy (FJHN): linkage analysis in 15 families, physical and transcriptional characterisation of the FJHN critical region on chromosome 16p11.2 and the analysis of seven candidate genes.</strong>
|
|
Europ. J. Hum. Genet. 11: 145-154, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12634862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12634862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12634862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200937" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Stiburkova2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stiburkova, B., Majewski, J., Sebesta, I., Zhang, W., Ott, J., Kmoch, S.
|
|
<strong>Familial juvenile hyperuricemic nephropathy: localization of the gene on chromosome 16p11.2--and evidence for genetic heterogeneity.</strong>
|
|
Am. J. Hum. Genet. 66: 1989-1994, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10780922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302936" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Turner2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Turner, J. J. O., Stacey, J. M., Harding, B., Kotanko, P., Lhotta, K., Puig, J. G., Roberts, I., Torres, R. J., Thakker, R. V.
|
|
<strong>UROMODULIN mutations cause familial juvenile hyperuricemic nephropathy.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1398-1401, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629136" 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.2002-021973" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Van Goor1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Goor, W., Kooiker, C. J., Mees, F. J. D.
|
|
<strong>An unusual form of renal disease associated with gout and hypertension.</strong>
|
|
J. Clin. Path. 24: 354-359, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5556122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5556122</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5556122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jcp.24.4.354" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Vylet'al2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vylet'al, P., Kublova, M., Kalbacova, M., Hodanova, K., Baresova, V., Stiburkova, B., Sikora, J., Hulkova, H., Zivny, J., Majewski, J., Simmonds, A., Fryns, J.-P., Venkat-Raman, G., Elleder, M., Kmoch, S.
|
|
<strong>Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome.</strong>
|
|
Kidney Int. 70: 1155-1169, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16883323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16883323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16883323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ki.5001728" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Williams2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Williams, S. E., Reed, A. A. C., Galvanovskis, J., Antignac, C., Goodship, T., Karet, F. E., Kotanko, P., Lhotta, K., Moriniere, V., Williams, P., Wong, W., Rorsman, P., Thakker, R. V.
|
|
<strong>Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum.</strong>
|
|
Hum. Molec. Genet. 18: 2963-2974, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19465746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19465746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19465746[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=19465746" 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/ddp235" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Yokota1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yokota, N., Yamanaka, H., Yamamoto, Y., Fujimoto, S., Eto, T., Tanaka, K.
|
|
<strong>Autosomal dominant transmission of gouty arthritis with renal disease in a large Japanese family.</strong>
|
|
Ann. Rheum. Dis. 50: 108-111, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847794</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1847794" 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/ard.50.2.108" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Zaucke2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zaucke, F., Boehnlein, J. M., Steffens, S., Polishchuk, R. S., Rampoldi, L., Fischer, A., Pasch, A., Boehm, C. W. A., Baasner, A., Attanasio, M., Hoppe, B., Hopfer, H., Beck, B. B., Sayer, J. A., Hildebrandt, F., Wolf, M. T. F.
|
|
<strong>Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression.</strong>
|
|
Hum. Molec. Genet. 19: 1985-1997, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20172860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20172860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20172860[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=20172860" 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/ddq077" 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">
|
|
Cassandra L. Kniffin - updated : 01/26/2021
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Carol A. Bocchini - updated : 10/18/2017<br>George E. Tiller - updated : 9/9/2013<br>George E. Tiller - updated : 9/5/2013<br>Cassandra L. Kniffin - updated : 2/13/2013<br>Marla J. F. O'Neill - updated : 9/15/2011<br>Marla J. F. O'Neill - updated : 10/15/2009<br>John A. Phillips, III - updated : 8/26/2003<br>Victor A. McKusick - updated : 6/30/2003<br>Victor A. McKusick - updated : 12/27/2002<br>Victor A. McKusick - updated : 2/12/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/2/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 02/26/2025
|
|
</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">
|
|
ckniffin : 02/25/2025<br>carol : 05/17/2022<br>carol : 02/22/2022<br>alopez : 02/09/2021<br>carol : 01/29/2021<br>ckniffin : 01/27/2021<br>ckniffin : 01/26/2021<br>carol : 10/19/2017<br>carol : 10/18/2017<br>carol : 08/01/2016<br>carol : 07/29/2016<br>ckniffin : 07/27/2016<br>carol : 03/25/2016<br>alopez : 9/9/2013<br>tpirozzi : 9/5/2013<br>carol : 9/5/2013<br>tpirozzi : 9/5/2013<br>carol : 4/4/2013<br>ckniffin : 2/13/2013<br>carol : 9/15/2011<br>terry : 9/15/2011<br>carol : 12/10/2010<br>terry : 10/21/2009<br>wwang : 10/16/2009<br>terry : 10/15/2009<br>terry : 9/10/2008<br>alopez : 8/26/2003<br>tkritzer : 7/15/2003<br>tkritzer : 7/7/2003<br>terry : 6/30/2003<br>cwells : 12/30/2002<br>terry : 12/27/2002<br>dholmes : 3/10/1998<br>mark : 2/18/1998<br>terry : 2/12/1998<br>alopez : 6/2/1997<br>mark : 9/17/1995<br>mimadm : 12/2/1994<br>davew : 8/5/1994<br>warfield : 3/28/1994<br>supermim : 3/16/1992<br>carol : 9/4/1991
|
|
</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> 162000
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TUBULOINTERSTITIAL KIDNEY DISEASE, AUTOSOMAL DOMINANT 1; ADTKD1
|
|
|
|
</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">
|
|
HYPERURICEMIC NEPHROPATHY, FAMILIAL JUVENILE, 1; HNFJ1<br />
|
|
FAMILIAL JUVENILE HYPERURICEMIC NEPHROPATHY; FJHN<br />
|
|
GOUTY NEPHROPATHY, FAMILIAL JUVENILE<br />
|
|
MEDULLARY CYSTIC KIDNEY DISEASE 2; MCKD2<br />
|
|
MEDULLARY CYSTIC KIDNEY DISEASE 2, AUTOSOMAL DOMINANT; ADMCKD2<br />
|
|
GLOMERULOCYSTIC KIDNEY DISEASE WITH HYPERURICEMIA AND ISOSTHENURIA
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 34149, 88950;
|
|
|
|
|
|
<strong>DO:</strong> 0060062;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
16p12.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Tubulointerstitial kidney disease, autosomal dominant, 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
162000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
UMOD
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
191845
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that autosomal dominant tubulointerstitial kidney disease-1 (ADTKD1) is caused by heterozygous mutation in the gene encoding uromodulin (UMOD; 191845) on chromosome 16p12.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Autosomal dominant tubulointerstitial kidney disease-1 (ADTKD1) is an adult-onset, slowly progressive renal disease characterized by elevated serum uric acid (hyperuricemia) due to low fractional excretion of uric acid, defective urinary concentrating ability, 'bland' urinary sediment, and progression to end-stage renal failure. Some patients may develop gouty arthritis, arterial hypertension, polydipsia/polyuria, or mild proteinuria. The onset of symptoms is usually in the third or fourth decade, although earlier and later onset have been reported. Renal ultrasound may show small or hyperechogenic kidneys. Renal biopsy shows variable abnormalities, including tubular atrophy, interstitial fibrosis, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. The median age at onset of end-stage renal disease (ESRD) is 56 years (range 50-65). There is significant inter- and intrafamilial variability, as well as incomplete penetrance, which hampers diagnosis (summary by Hart et al., 2002, Ayasreh et al., 2018, and Devuyst et al., 2019). </p><p><strong><em>Genetic Heterogeneity of Autosomal Dominant Tubulointerstitial Kidney Disease</em></strong></p><p>
|
|
ADTKD2 (174000) is caused by mutation in the MUC1 gene (158340) on chromosome 1q22; ADTKD3 (137920) is caused by mutation in the HNF1B gene (189907) on chromosome 17q12; ADTKD4 (613092) is caused by mutation in the renin gene (REN; 179820) on chromosome 1q32; ADTKD5 (617056) is caused by mutation in the SEC61A1 gene (609213) on chromosome 3q21; and ADTKD6 (621106) is caused by mutation in the APOA4 gene (107690) on chromosome 11q23.</p><p>See 614227 for a possibly distinct form of ADTKD tentatively mapped to chromosome 2p22.1-p21.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The terms 'familial juvenile hyperuricemic nephropathy' (FJHN, HNFJ), 'medullary cystic kidney disease' (MCKD), 'glomerulocystic kidney disease' (GCKD), 'tubulointerstitial nephritis,' and 'hereditary interstitial kidney disease,' among others, have all been used to describe this phenotype. In a review, Devuyst et al. (2019) noted that the use of these confusing and inconsistent terms has hampered the detection and study of this renal disorder, which is genetically heterogeneous. These authors proposed the adoption of a unifying terminology, namely 'autosomal dominant tubulointerstitial kidney disease' (ADTKD), to refer to these diseases. The usual clinical manifestations of ADTKD in general are adult onset, progressive loss of kidney function, and variable proteinuria or microscopic hematuria. Renal biopsy shows interstitial fibrosis and tubular atrophy with a thickening and lamellation of tubular membranes, sometimes with secondary glomerulosclerosis. There may be microcystic tubular dilatations or renal cysts, but these findings are not pathognomonic. Although renal biopsy is important, Devuyst et al. (2019) stated that it is not possible to make a diagnosis of ADTKD based solely on biopsy findings. Genetic testing using a candidate gene panel may be the most effective diagnostic method (see also Ayasreh et al., 2018). Due to the nonspecific nature of the clinical and pathologic findings, ADTKD is likely underdiagnosed (summary by Olinger et al., 2020). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Early Reports of Families With Unknown Mutations</em></strong></p><p>
|
|
Rosenbloom et al. (1967) described a family in which multiple males in 3 generations died from renal failure at a relatively early age. All had hyperuricemia early in the course of the disease and developed gout. No distinctive histologic findings were yielded by renal biopsy. Transmission from father to son excluded X-linked inheritance. See McKusick (1974) for pedigree of the family of Rosenbloom et al. (1967). Duncan and Dixon (1960), Van Goor et al. (1971), and Simmonds et al. (1980) reported families with hyperuricemia and gout associated with renal disease. </p><p>Leumann (1972) and Leumann and Wegmann (1983) observed chronic interstitial nephropathy with disproportionate hyperuricemia in 2 girls and their mother. The mother suffered from gout beginning at age 20 years and required dialysis by age 34. The authors suggested that 'the severity of renal destruction by gout has been overestimated in the past and that families like the one described have been considered as gouty nephropathy.' Calabrese et al. (1990) and Cameron et al. (1990) reported further families. They emphasized the importance of investigating all sibs of such patients and of treatment with allopurinol of family members with a reduced fractional clearance of urate. Deterioration of renal function in patients who did not consistently take allopurinol and stability of renal function in compliers was the experience of Cameron et al. (1990) in 6 kindreds. Moro et al. (1991) found hyperuricemia associated with a grossly reduced fractional uric acid clearance in 2 children who did not yet have other signs of renal damage. They emphasized the usefulness of early recognition since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion. </p><p>Saeki et al. (1995) found autosomal dominant inheritance in a Japanese family. They reported on 2 sisters who had gout and renal insufficiency. </p><p>McBride et al. (1997) stated that the Guy's Hospital group in London had identified 79 subjects with familial juvenile hyperuricemic nephropathy. They studied 36 children ranging in age from 3 to 17 years. Three were index cases. The other 33 were among 116 'healthy' relatives investigated from FJHN families in which the index case had presented initially with gout, renal disease, or both--generally with a strong family history spanning 2 or 3 generations (Moro et al., 1991). McBride et al. (1997) found a number of these children from kindreds who had hyperuricemia associated with a grossly reduced fractional uric acid clearance (FE(ur)) but normal renal function. (The FE(ur) is uric acid clearance factored by creatinine clearance x 100; mean for UK children = 18.4 +/- 5.1%.) The FE(ur) was 5.0 in affected children with normal or only mildly impaired renal function. These studies provided compelling evidence that hyperuricemia is a primary event in this type of nephropathy. The investigators underlined the importance of presymptomatic detection of the disorder, since in patients diagnosed before the onset of severe renal disease (creatinine clearance greater than 50 ml/min), allopurinol has ameliorated the hitherto rapid progression of the renal disease seen in earlier generations for up to 27 years (Moro et al., 1991). </p><p><strong><em>Families with Mutations in the UMOD Gene</em></strong></p><p>
|
|
Massari et al. (1980) described a family in which 9 individuals had renal disease characterized mainly by hyperuricemia. Three had gouty arthritis. Renal biopsy showed focal global and segmental sclerosis of glomeruli, occasional hypercellularity, foci of atrophic tubules, chronic interstitial inflammation, and folding and wrinkling of the glomerular basement membrane without electron-dense deposits. </p><p>Hart et al. (2002) reported 4 unrelated families with a similar renal disease characterized by juvenile onset of hyperuricemia, polyuria, gout, and progressive renal insufficiency that was tubulointerstitial in origin. Family 4 had previously been reported by Massari et al. (1980). In all patients, the disorder was associated with impaired urinary concentrating ability, which was postulated to result in a compensatory increase in proximal tubular reabsorption of uric acid and hyperuricemia. Renal biopsies showed tubular atrophy and interstitial fibrosis. Global glomerulosclerosis was also observed, although there was no evidence of glomerulonephritis. Necroscopy showed sheathing of the renal tubules by dense acellular hyaline fibrous tissue that likely represented abnormal deposition of the UMOD protein. Three families (families 1, 2, and 4) had a clinical diagnosis of familial juvenile hyperuricemic nephropathy (FJHN, HNFJ). Medullary cysts were present in 1 family (family 3), consistent with a clinical diagnosis of medullary cystic kidney disease (MCKD). </p><p>Stiburkova et al. (2003) studied 3 Belgian brothers (family BE2) who reportedly developed the first symptoms of hyperuricemia and gouty arthritis after the age of 30 years; allopurinol treatment was started at that time. They had onset of renal failure between 45 and 50 years of age, with renal echography showing small hyperechogenic kidneys. Between 55 and 60 years of age, they developed arterial hypertension and progressive preterminal renal failure with elevated creatinine levels. Linkage analysis was consistent with linkage to chromosome 16p11. Vylet'al et al. (2006) restudied family BE2 and reported that 2 of the 3 brothers had earlier onset of the disease at age 20 years. The eldest brother had undergone successful kidney transplantation at age 65 years, and the middle brother began hemodialysis at age 60 years. </p><p>Dahan et al. (2003) reported 11 unrelated families with ADTKD1, 10 of which were of European descent and 1 of Moroccan descent. The 2 largest families had 11 and 7 affected individuals, respectively. At the time of examination, 17 patients had reached end-stage renal failure between ages 25 and 64 years, and 15 had chronic renal failure. Seven had preserved renal function, all of whom were younger than 34 years. Eighteen individuals had a history of gout with onset between 8 and 38 years. Renal biopsy, available from 6 individuals from 3 families, showed chronic interstitial nephritis with tubular atrophy and marked thickening of the tubular basement membrane. Renal imaging showed small cysts in 12 individuals with renal failure. Laboratory studies showed variably decreased urinary excretion of uromodulin compared to controls. </p><p>Lens et al. (2005) reported 4 Spanish families with variable manifestations of ADTKD1, demonstrating the phenotypic heterogeneity of the disorder. Family 4 had previously been reported by Rezende-Lima et al. (2004) as having medullary cystic kidney disease, although those authors noted that cyst formation may be a nonspecific secondary effect. There were 9 individuals in family 1 of Lens et al. (2005) who had highly variable clinical manifestations. Most had onset of hyperuricemia between 27 and 52 years of age, sometimes associated with gout. Four developed renal insufficiency between 29 and 57 years, but only 2 of these had end-stage renal disease after age 64. Four patients had arterial hypertension. Renal ultrasound showed medullary cysts in 2 patients with end-stage renal disease; renal biopsy in 1 of these patients showed chronic interstitial nephritis with marked thickening of tubular membranes. Other mutation carriers in the family did not have renal cysts. Two patients, ages 28 and 32, had only borderline increased serum uric acid without other manifestations. The findings suggested a clinical diagnosis of medullary cystic kidney disease. A 54-year-old man in family 2 had onset of hyperuricemia and gout at 15 and 31 years of age, respectively, and developed renal insufficiency at 44 years. Two older family members had end-stage renal disease at 51 and 67 years, respectively. Renal cysts were not present in this family; they were diagnosed with hyperuricemic nephropathy. Two sisters in family 3 had onset of hyperuricemia and renal insufficiency as teenagers. Renal biopsy showed dilatation of Bowman space in most glomeruli with rudimentary glomerular tufts without tubular dilatations; these findings were consistent with a diagnosis of glomerulocystic kidney disease. Their father and his sister developed end-stage renal disease at 55 and 62 years of age, respectively. </p><p>Williams et al. (2009) reported 6 unrelated probands (families 5, 6, 9, 11, 15, and 20), ranging from 14 to 72 years of age, with ADTKD1 confirmed by genetic analysis. Including affected family members, 13 individuals were identified. All patients had low fractional excretion of uric acid, with hyperuricemia in 73% and gout in 31%. Small or atrophic kidneys were found in 23% of patients, and cysts in 8%. About half had renal insufficiency, and 39% had end-stage renal failure. Two patients, including the 72-year-old, had a renal transplant. </p><p>Ayasreh et al. (2018) reported 9 unrelated Spanish families in which 44 individuals had ADTKD1 confirmed by genetic analysis. The majority of patients (87%) had hyperuricemia with a mean age at onset of 36.6 years. Other common features included gout (24%), hypertension (63%), polyuria/polydipsia (30%/24%), and proteinuria (10%). End-stage renal disease developed at an average age of 56 years. In 1 consanguineous family (F36), 2 members with a homozygous mutation developed end-stage renal disease at a mean age of 38.5 years, earlier than usual. Renal ultrasound showed small hyperechogenic kidneys in about 50% of those studied; cysts were found in 2 patients. Two patients had renal biopsies that showed tubular atrophy and interstitial fibrosis; 1 also had microcystic dilatation of the tubules. There was marked inter- and intrafamilial phenotypic variability, and the authors emphasized that neither hyperuricemia nor cysts represent hallmarks of the disease. Late onset of the disorder, incomplete penetrance, environmental factors, and other genetic or epigenetic changes may partially explain the variability. </p><p>Olinger et al. (2020) identified 303 patients from 216 families with ADTKD1 confirmed by genetic analysis. The families were ascertained from 2 large cohorts from Europe and the United States comprising 726 patients from 585 families, and thus represented 38.4% of families. The mean age at presentation was 42 years (range 27-53); most patients had hyperuricemia and gout. End-stage kidney disease occurred at a mean age of 46 years (range 39-57). Regarding pathogenesis, the authors noted that abnormal accumulation of UMOD in the endoplasmic reticulum (ER) of the distal renal tubules may induce ER stress and disrupt function. Defective urinary concentration resulting in polyuria and polydipsia most likely results from impaired activity of the thick ascending loop of Henle, which causes plasma volume contraction with compensatory reabsorption activity of the proximal tubule, including upregulation of Na(+)-coupled urate transporters. This results in hyperuricemia that is unique to ADTKD1. Olinger et al. (2020) provided a diagnostic algorithm based on simple scoring of clinical features, including urinary UMOD levels, hyperuricemia, and gout. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of ADTKD1 in the families reported by Lens et al. (2005) and Ayasreh et al. (2018) was consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomewide linkage mapping in a 4-generation Italian pedigree with adult-onset renal disease, Scolari et al. (1999) identified a disease locus, which they termed 'autosomal dominant medullary cystic disease-2' (MCKD2), on chromosome 16p12. The family fulfilled the typical diagnostic criteria of ADTKD1, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 showed a maximum 2-point lod score of 3.68, and the defined critical region spanned 10.5 cM, between D16S500 and SCNN1B1-2. Scolari et al. (1999) noted that the UMOD gene, which maps to the critical region, is expressed mainly in the kidney, where it is localized to the epithelial cells of the thick ascending limb (TAL) of the Henle loop. Uromodulin has been functionally associated with the water nonpermeability of the TAL, a function that is altered in this disorder; UMOD was considered a candidate gene. </p><p>By linkage analysis of 2 families with ADTKD, Hart et al. (2002) identified a candidate region between 16p13.11 (D16S499) and 16p12.2 (D16S403). The authors noted that this region did not overlap with a region on 16p12 identified by Kamatani et al. (2000) in a large Japanese family (see below). </p><p>Stacey et al. (2003) pursued linkage studies in 7 European families with ADTKD and used 11 chromosome 16p13-p11 polymorphic loci. Cosegregation between these polymorphic loci and the disorder was observed in 5 of the families; linkage was established between ADTKD and 6 loci. </p><p>Vylet'al et al. (2006) performed linkage analysis in 19 families with variable manifestations of ADTKD and found linkage to chromosome 16p11.2 in 9 of the families. Quantitative analysis showed that UMOD excretion was significantly reduced in almost all affected individuals, regardless of which linkage group they belonged to; 1 family (CZ3), which did not link to any known loci, showed normal UMOD excretion. </p><p><strong><em>Genetic Heterogeneity</em></strong></p><p>
|
|
Yokota et al. (1991) described a large Japanese family with autosomal dominant transmission of gouty arthritis with renal disease. At least 20 members of the family were affected. Kamatani et al. (2000) obtained DNA from 13 affected and 18 unaffected members. A genomewide search initially showed evidence of linkage for a marker on 16p. Subsequently, the same subjects were genotyped for 12 additional markers spanning approximately 30 cM on the short arm of chromosome 16. They obtained a maximum 2-point lod score of 6.04 at theta = 0.0 with the marker D16S401; multipoint linkage analysis yielded a maximum lod score of 6.14 with markers D16S401 and D16S3113, and established a minimum candidate interval of approximately 9 cM in the 16p12 region. </p><p>Stacey et al. (2003) excluded linkage to chromosome 16p13-p11 in 2 European families with ADTKD, thereby demonstrating genetic heterogeneity (see 614227). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 4 unrelated families with ADTKD1, Hart et al. (2002) identified 4 different heterozygous mutations in exon 4 of the UMOD gene (191845.0001-191845.0004). The mutations, which were found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the families. Three families (families 1, 2, and 4) had a clinical diagnosis of familial juvenile hyperuricemic nephropathy (FJHN, HNFJ), whereas family 3 was diagnosed clinically with medullary cystic kidney disease (MCKD). Family 4 had previously been reported by Massari et al. (1980). Functional studies of the variants and studies of patient cells were not performed, but the authors postulated that the mutations caused tertiary structural changes in the uromodulin protein that could alter cytokine binding and ultimately lead to fibrosis and progressive renal failure. The report established that the clinical entities of FJHN and MCKD not only share clinical features, but are also either allelic or variable manifestations of the same disease. Noting that hyperuricemia and medullary cysts are variable features and that the conditions result from mutations in the same gene, the authors suggested the designation 'uromodulin-associated kidney disease.' </p><p>In 5 unrelated kindreds with ADTKD1, 2 from Austria and 3 from Spain, Turner et al. (2003) identified 5 heterozygous missense mutations in the UMOD gene (191845.0005-191845.0009) that altered evolutionary conserved residues. These mutations were not found in 110 alleles from 55 unrelated normal individuals. Functional studies of the variants were not performed, but the authors postulated a loss-of-function effect. The families had previously been reported by Stacey et al. (2003). </p><p>In affected members of 4 unrelated Italian families with variable manifestations of ADTKD1, Rampoldi et al. (2003) identified heterozygous missense mutations in the UMOD gene (see, e.g., C315R, 191845.0010 and C148W, 191845.0015). All mutations affected highly conserved cysteine residues and were predicted to affect protein structure. Immunohistochemistry of kidney biopsies revealed dense intracellular accumulation of uromodulin in tubular epithelia of the thick ascending limb of Henle loop. Electron microscopy showed accumulation of dense fibrillar material within the endoplasmic reticulum, and patient urine samples consistently showed a severe reduction of excreted uromodulin. Experiments in transfected cells showed that all 4 mutations caused a delay in protein export to the plasma membrane due to a longer retention time in the ER. The protein maturation impairment and retention in the ER, which may trigger ubiquitination, suggested a pathogenetic mechanism leading to these kidney diseases. Rampoldi et al. (2003) postulated that hyperuricemia is a secondary effect of volume contraction resulting from UMOD dysfunction in the thick ascending loop of Henle. Three families had a clinical diagnosis of MCKD/FJHN (including a family previously reported by Scolari et al., 1999), and 1 family had a clinical diagnosis of glomerulocystic kidney disease (GCKD), thus demonstrating that these clinical entities are allelic and likely are different manifestations of the same disorder. </p><p>In patients from 11 families with ADTKD1, Dahan et al. (2003) identified 11 different heterozygous mutations in the UMOD gene, including 10 novel mutations (see, e.g., 191845.0012). There were 10 missense mutations and 1 in-frame deletion. All of the mutations occurred at highly conserved residues in exon 4, and 5 of the mutations affected a conserved cysteine residue. The families were ascertained from a larger group of 25 families with a similar phenotype; thus, UMOD mutations were found in 44% of families. Medullary cysts were identified in 9 patients from 8 families. Patient kidney samples showed abnormal uromodulin immunostaining within enlarged or cystic profiles in tubules in the thick ascending loop, and not at the apical membrane as observed in controls. Mutant UMOD was not found in proximal tubules. Patients also showed decreased urinary excretion of wildtype uromodulin. These findings indicated that mutant uromodulin accumulates within renal tubular cells in patients with UMOD mutations. Dahan et al. (2003) concluded that the clinical diagnoses of FJHN and MCKD2 represent 2 facets of the same disease entity. </p><p>In 14 affected members of a large consanguineous Spanish family with ADTKD1, Rezende-Lima et al. (2004) identified a C255Y mutation in the UMOD gene (191845.0008). Eleven family members were heterozygous for the mutation, whereas 3 were homozygous. The homozygous individuals had earlier disease onset than the heterozygous carriers, but the report demonstrated that homozygosity for UMOD mutations is not lethal. The clinical phenotype was consistent with medullary cystic kidney disease (MCKD), although the authors noted that cyst formation may be a nonspecific secondary effect. This family was also reported as family F4 by Lens et al. (2005). </p><p>In affected members of 2 apparently unrelated Spanish families with ADTKD1, Lens et al. (2005) identified the same heterozygous missense mutation in the UMOD gene (Q316P; 191845.0014). The mutation segregated with the phenotype in the families and was not found in 100 control chromosomes. Family 1 had a clinical phenotype consistent with MCKD, and family 2 had a clinical phenotype consistent with FJHN. The demonstration of the same mutation in both families further supported that MCKD and FJHN are the same disease entity. A third Spanish family (family 3), with a clinical phenotype consistent with GCKD, carried a different heterozygous missense mutation (C300G; 191845.0009). </p><p>Vylet'al et al. (2006) sequenced the UMOD gene in 19 families with variable manifestations of ADTKD1 and identified heterozygous mutations in 6 families, 5 of which had been previously reported (kindred 6 from McBride et al., 1998; kindreds A and B from Stiburkova et al., 2000; Fairbanks et al., 2002; and family BE2 from Stiburkova et al., 2003) (see, e.g., 191845.0006 and 191845.0011). </p><p>In 6 of 17 probands with ADTKD who were studied for UMOD mutations, Williams et al. (2009) identified 6 different heterozygous missense mutations in the UMOD gene (see, e.g., D196N, 191845.0016). In vitro functional studies of some of the mutations expressed in HeLa cells showed that the mutant uromodulins had significantly delayed maturation compared to wildtype, with abnormal protein retention in the ER and reduced or absent expression at the plasma membrane. There were different effects allowing the identification of 2 mutation groups: group A (including mutants C32W, D196N, and G488R) had 50% maturation compared to wildtype with some expression at the plasma membrane, whereas group B (including mutants C126R, 191845.0006; N128S, 191845.0007; and C223R) had 25% maturation compared to wildtype and absence of expression at the plasma membrane. There were no phenotypic differences between patients with group A and group B mutations. The findings suggested that abnormal folding of the mutant proteins resulted in protein retention in the ER, which may trigger apoptosis and underlie the mechanism for disease pathogenesis. </p><p>In affected members of 10 unrelated families with ADTKD1, Zaucke et al. (2010) identified 7 novel and 3 previously reported heterozygous missense mutations in the UMOD gene (see, e.g., 191845.0009 and 191845.0013). Most of the mutations affected conserved cysteine residues. The number of UMOD-positive primary cilia in renal biopsy samples from 2 of the patients was significantly decreased compared to control samples. The authors suggested that this defect may contribute to cyst formation. The families were ascertained from a cohort of 44 families with nephropathy from western Europe and the United States who underwent direct sequencing of the UMOD gene. </p><p>Olinger et al. (2020) identified 106 unique heterozygous mutations in the UMOD gene in 303 patients from 216 families with ADTKD1. The families were ascertained from 2 large cohorts from Europe and the United States comprising 726 patients from 585 families, and thus represented 38.4% of families. The majority (95.3%) of the mutations were missense, and most occurred in exon 3. About half involved cysteine bonds. </p><p>In a review article on the pathogenesis of ADTKD1, Devuyst et al. (2019) concluded that the disorder results from a toxic gain-of-function effect due to abnormal accumulation of mutant UMOD in the ER, where it is believed to stimulate the unfolded protein response and activate pathways of ER stress. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a genetic study of 56 Spanish families with a clinical diagnosis of ADTKD, Ayasreh et al. (2018) found that 25 (45%) carried pathogenic mutations in either the UMOD gene (9 families, 36%) or MUC1 gene (16 families, 64%). These findings suggested that MUC1 mutations are the most common cause of the disorder in that population. No pathogenic mutations were identified in REN (179820) or HNF1B (189907). </p><p>In a genetic study of 2 large cohorts from Europe and the United States comprising 726 patients from 585 families with ADTKD, Olinger et al. (2020) found that 303 patients from 216 families (38.4%) had mutations in the UMOD gene. MUC1 mutations were found in 104 patients from 93 families (21%). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Bernascone et al. (2010) generated a transgenic mouse model for the UMOD-associated kidney diseases HNFJ and MCKD. The transgenic mice, which had a Umod C147W mutation corresponding to the human UMOD C148W mutation (191845.0015), recapitulated most of the features observed in patients with UMOD kidney disease, with urinary concentrating defect of renal origin and progressive renal injury, i.e., tubulointerstitial fibrosis with inflammatory cell infiltration, tubule dilation, and specific damage of the thick ascending limb of the loop of Henle (TAL), leading to mild renal failure. As observed in patients with the C148W mutation, the mutant mice showed a marked reduction in urinary uromodulin excretion. Mutant uromodulin was retained in the endoplasmic reticulum (ER) of expressing cells, leading to ER hyperplasia. The authors suggested that impaired TAL function is a consequence of a gain-of-function effect of UMOD mutations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ayasreh, N., Bullich, G., Miquel, R., Furlano, M., Ruiz, P., Lorente, L., Valero, O., Garcia-Gonzalez, M. A., Arhda, N., Garin, I., Martinez, V., Perez-Gomez, V., Fulladosa, X., Arroyo, D., Martinez-Vea, A., Espinosa, M., Ballarin, J., Ars, E., Torra, R.
|
|
<strong>Autosomal dominant tubulointerstitial kidney disease: clinical presentation of patients with ADTKD-UMOD and ADTKD-MUC1.</strong>
|
|
Am. J. Kidney Dis. 72: 411-418, 2018.
|
|
|
|
|
|
[PubMed: 29784615]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1053/j.ajkd.2018.03.019]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernascone, I., Janas, S., Ikehata, M., Trudu, M., Corbelli, A., Schaeffer, C., Rastaldi, M. P., Devuyst, O., Rampoldi, L.
|
|
<strong>A transgenic mouse model for uromodulin-associated kidney diseases shows specific tubulo-interstitial damage, urinary concentrating defect and renal failure.</strong>
|
|
Hum. Molec. Genet. 19: 2998-3010, 2010.
|
|
|
|
|
|
[PubMed: 20472742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq205]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Calabrese, G., Simmonds, H. A., Cameron, J. S., Davies, P. M.
|
|
<strong>Precocious familial gout with reduced fractional urate clearance and normal purine enzymes.</strong>
|
|
Quart. J. Med. 75: 441-450, 1990.
|
|
|
|
|
|
[PubMed: 2388995]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cameron, J. S., Ogg, C. S., Moro, F., Chantler, C., Simmonds, H. A.
|
|
<strong>Precocious familial gout. (Letter)</strong>
|
|
Lancet 336: 745 only, 1990.
|
|
|
|
|
|
[PubMed: 1975911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0140-6736(90)92235-a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dahan, K., Devuyst, O., Smaers, M., Vertommen, D., Loute, G., Poux, J. M., Viron, B., Jacquot, C., Gagnadoux, M. F., Chauveau, D., Buchler, M., Cochat, P., Cosyns, J. P., Mougenot, B., Rider, M. H., Antignac, C., Verellen-Dumoulin, C., Pirson, Y.
|
|
<strong>A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.</strong>
|
|
J. Am. Soc. Nephrol. 14: 2883-2893, 2003.
|
|
|
|
|
|
[PubMed: 14569098]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/01.asn.0000092147.83480.b5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Devuyst, O., Olinger, E., Weber, S., Eckardt, K.-U., Kmoch, S., Rampoldi, L., Bleyer, A. J.
|
|
<strong>Autosomal dominant tubulointerstitial kidney disease.</strong>
|
|
Nat. Rev. Dis. Primers. 5: 60, 2019. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 31488840]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41572-019-0109-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duncan, H., Dixon, A. C. J.
|
|
<strong>Gout, familial hyperuricemia, and renal disease.</strong>
|
|
Quart. J. Med. 29: 127-135, 1960.
|
|
|
|
|
|
[PubMed: 13818629]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fairbanks, L. D., Cameron, J. S., Venkat-Raman, G., Rigden, S. P. A., Rees, L., Van't Hoff, W., Mansell, M., Pattison, J., Goldsmith, D. J. A., Simmonds, H. A.
|
|
<strong>Early treatment with allopurinol in familial juvenile hyperuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.</strong>
|
|
Quart. J. Med. 95: 597-607, 2002.
|
|
|
|
|
|
[PubMed: 12205338]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/qjmed/95.9.597]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hart, T. C., Gorry, M. C., Hart, P. S., Woodard, A. S., Shihabi, Z., Sandhu, J., Shirts, B., Xu, L., Zhu, H., Barmada, M. M., Bleyer, A. J.
|
|
<strong>Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.</strong>
|
|
J. Med. Genet. 39: 882-892, 2002.
|
|
|
|
|
|
[PubMed: 12471200]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.39.12.882]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kamatani, N., Moritani, M., Yamanaka, H., Takeuchi, F., Hosoya, T., Itakura, M.
|
|
<strong>Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.</strong>
|
|
Arthritis Rheum. 43: 925-929, 2000.
|
|
|
|
|
|
[PubMed: 10765940]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1529-0131(200004)43:4<925::AID-ANR26>3.0.CO;2-B]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lens, X. M., Banet, J. F., Outeda, P., Barrio-Lucia, V.
|
|
<strong>A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.</strong>
|
|
Am. J. Kidney Dis. 46: 52-57, 2005.
|
|
|
|
|
|
[PubMed: 15983957]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1053/j.ajkd.2005.04.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leumann, E. P., Wegmann, W.
|
|
<strong>Familial nephropathy with hyperuricemia and gout.</strong>
|
|
Nephron 34: 51-57, 1983.
|
|
|
|
|
|
[PubMed: 6855996]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000182979]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leumann, E.
|
|
<strong>Personal Communication.</strong>
|
|
Zurich, Switzerland 1972.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Massari, P. U., Hsu, C. H., Barnes, R. V., Fox, I. H., Gikas, P. W., Weller, J. M.
|
|
<strong>Familial hyperuricemia and renal disease.</strong>
|
|
Arch. Intern. Med. 140: 680-684, 1980.
|
|
|
|
|
|
[PubMed: 7396593]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McBride, M. B., Rigden, S., Haycock, G. B., Dalton, N., Van't Hoff, W., Rees, L., Venkat-Raman, G. V., Moro, F., Ogg, C. S., Cameron, J. S., Simmonds, H. A.
|
|
<strong>Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children.</strong>
|
|
Pediat. Nephrol. 12: 357-364, 1998.
|
|
|
|
|
|
[PubMed: 9686952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004670050466]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McBride, M. B., Simmonds, H. A., Moro, F.
|
|
<strong>Familial renal disease or familial juvenile hyperuricaemic nephropathy?</strong>
|
|
J. Inherit. Metab. Dis. 20: 351-353, 1997.
|
|
|
|
|
|
[PubMed: 9266353]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/a:1005365625778]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A.
|
|
<strong>Familial nephropathy with gout.</strong>
|
|
Birth Defects Orig. Art. Ser. X(4): 178-179, 1974.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moro, F., Ogg, C. S., Simmonds, H. A., Cameron, J. S., Chantler, C., McBride, M. B., Duley, J. A., Davies, P. M.
|
|
<strong>Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.</strong>
|
|
Clin. Nephrol. 35: 263-269, 1991.
|
|
|
|
|
|
[PubMed: 1873940]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moro, F., Simmonds, H. A., Cameron, J. S., Ogg, C. S., Williams, G. D., McBride, M. B., Davis, P. M.
|
|
<strong>Does allopurinol affect the progression in familial juvenile gouty nephropathy?</strong>
|
|
Adv. Exp. Med. Biol. 309A: 199-202, 1991.
|
|
|
|
|
|
[PubMed: 1789208]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/978-1-4899-2638-8_45]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Olinger, E., Hofmann, P., Kidd, K., Dufour, I., Belge, H., Schaeffer, C., Kipp, A., Bonny, O., Deltas, C., Demoulin, N., Fehr, T., Fuster, D. G., and 21 others.
|
|
<strong>Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.</strong>
|
|
Kidney Int. 98: 717-731, 2020.
|
|
|
|
|
|
[PubMed: 32450155]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.kint.2020.04.038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rampoldi, L., Caridi, G., Santon, D., Boaretto, F., Bernascone, I., Lamorte, G., Tardanico, R., Dagnino, M., Colussi, G., Scolari, F., Ghiggeri, G. M., Amoroso, A., Casari, G.
|
|
<strong>Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics.</strong>
|
|
Hum. Molec. Genet. 12: 3369-3384, 2003.
|
|
|
|
|
|
[PubMed: 14570709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg353]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rezende-Lima, W., Parreira, K. S., Garcia-Gonzalez, M., Riveira, E., Banet, J. F., Lens, X. M.
|
|
<strong>Homozygosity for uromodulin disorders: FJHN and MCKD-type 2.</strong>
|
|
Kidney Int. 66: 558-563, 2004.
|
|
|
|
|
|
[PubMed: 15253706]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1523-1755.2004.00774.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenbloom, F. M., Kelley, W. N., Carr, A. A., Seegmiller, J. E.
|
|
<strong>Familial nephropathy and gout in a kindred. (Abstract)</strong>
|
|
Clin. Res. 15: 270 only, 1967.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saeki, A., Hosoya, T., Okabe, H., Saji, M., Tabe, A., Ichida, K., Itoh, K., Joh, K., Sakai, O.
|
|
<strong>Newly discovered familial juvenile gouty nephropathy in a Japanese family.</strong>
|
|
Nephron 70: 359-366, 1995.
|
|
|
|
|
|
[PubMed: 7477627]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000188618]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scolari, F., Puzzer, D., Amoroso, A., Caridi, G., Ghiggeri, G. M., Maiorca, R., Aridon, P., De Fusco, M., Ballabio, A., Casari, G.
|
|
<strong>Identification of a new locus for medullary cystic disease, on chromosome 16p12.</strong>
|
|
Am. J. Hum. Genet. 64: 1655-1660, 1999.
|
|
|
|
|
|
[PubMed: 10330352]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302414]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Simmonds, H. A., Warren, D. J., Cameron, J. S., Potter, C. F., Farebrother, D. A.
|
|
<strong>Familial gout and renal failure in young women.</strong>
|
|
Clin. Nephrol. 14: 176-182, 1980.
|
|
|
|
|
|
[PubMed: 7428192]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stacey, J. M., Turner, J. J. O., Harding, B., Nesbit, M. A., Kotanko, P., Lhotta, K., Puig, J. G., Torres, R. J., Thakker, R. V.
|
|
<strong>Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13.</strong>
|
|
J. Clin. Endocr. Metab. 88: 464-470, 2003.
|
|
|
|
|
|
[PubMed: 12519891]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021268]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stiburkova, B., Majewski, J., Hodanova, K., Ondrova, L., Jerabkova, M., Zikanova, M., Vylet'al, P., Sebesta, I., Marinaki, A., Simmonds, A., Matthijs, G., Fryns, J.-P., Torres, R., Puig, J. G., Ott, J., Kmoch, S.
|
|
<strong>Familial juvenile hyperuricaemic nephropathy (FJHN): linkage analysis in 15 families, physical and transcriptional characterisation of the FJHN critical region on chromosome 16p11.2 and the analysis of seven candidate genes.</strong>
|
|
Europ. J. Hum. Genet. 11: 145-154, 2003.
|
|
|
|
|
|
[PubMed: 12634862]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200937]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stiburkova, B., Majewski, J., Sebesta, I., Zhang, W., Ott, J., Kmoch, S.
|
|
<strong>Familial juvenile hyperuricemic nephropathy: localization of the gene on chromosome 16p11.2--and evidence for genetic heterogeneity.</strong>
|
|
Am. J. Hum. Genet. 66: 1989-1994, 2000.
|
|
|
|
|
|
[PubMed: 10780922]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302936]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Turner, J. J. O., Stacey, J. M., Harding, B., Kotanko, P., Lhotta, K., Puig, J. G., Roberts, I., Torres, R. J., Thakker, R. V.
|
|
<strong>UROMODULIN mutations cause familial juvenile hyperuricemic nephropathy.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1398-1401, 2003.
|
|
|
|
|
|
[PubMed: 12629136]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021973]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Goor, W., Kooiker, C. J., Mees, F. J. D.
|
|
<strong>An unusual form of renal disease associated with gout and hypertension.</strong>
|
|
J. Clin. Path. 24: 354-359, 1971.
|
|
|
|
|
|
[PubMed: 5556122]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jcp.24.4.354]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vylet'al, P., Kublova, M., Kalbacova, M., Hodanova, K., Baresova, V., Stiburkova, B., Sikora, J., Hulkova, H., Zivny, J., Majewski, J., Simmonds, A., Fryns, J.-P., Venkat-Raman, G., Elleder, M., Kmoch, S.
|
|
<strong>Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome.</strong>
|
|
Kidney Int. 70: 1155-1169, 2006.
|
|
|
|
|
|
[PubMed: 16883323]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ki.5001728]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Williams, S. E., Reed, A. A. C., Galvanovskis, J., Antignac, C., Goodship, T., Karet, F. E., Kotanko, P., Lhotta, K., Moriniere, V., Williams, P., Wong, W., Rorsman, P., Thakker, R. V.
|
|
<strong>Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum.</strong>
|
|
Hum. Molec. Genet. 18: 2963-2974, 2009.
|
|
|
|
|
|
[PubMed: 19465746]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp235]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yokota, N., Yamanaka, H., Yamamoto, Y., Fujimoto, S., Eto, T., Tanaka, K.
|
|
<strong>Autosomal dominant transmission of gouty arthritis with renal disease in a large Japanese family.</strong>
|
|
Ann. Rheum. Dis. 50: 108-111, 1991.
|
|
|
|
|
|
[PubMed: 1847794]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/ard.50.2.108]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zaucke, F., Boehnlein, J. M., Steffens, S., Polishchuk, R. S., Rampoldi, L., Fischer, A., Pasch, A., Boehm, C. W. A., Baasner, A., Attanasio, M., Hoppe, B., Hopfer, H., Beck, B. B., Sayer, J. A., Hildebrandt, F., Wolf, M. T. F.
|
|
<strong>Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression.</strong>
|
|
Hum. Molec. Genet. 19: 1985-1997, 2010.
|
|
|
|
|
|
[PubMed: 20172860]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq077]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 01/26/2021<br>Carol A. Bocchini - updated : 10/18/2017<br>George E. Tiller - updated : 9/9/2013<br>George E. Tiller - updated : 9/5/2013<br>Cassandra L. Kniffin - updated : 2/13/2013<br>Marla J. F. O'Neill - updated : 9/15/2011<br>Marla J. F. O'Neill - updated : 10/15/2009<br>John A. Phillips, III - updated : 8/26/2003<br>Victor A. McKusick - updated : 6/30/2003<br>Victor A. McKusick - updated : 12/27/2002<br>Victor A. McKusick - updated : 2/12/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/2/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 02/26/2025<br>ckniffin : 02/25/2025<br>carol : 05/17/2022<br>carol : 02/22/2022<br>alopez : 02/09/2021<br>carol : 01/29/2021<br>ckniffin : 01/27/2021<br>ckniffin : 01/26/2021<br>carol : 10/19/2017<br>carol : 10/18/2017<br>carol : 08/01/2016<br>carol : 07/29/2016<br>ckniffin : 07/27/2016<br>carol : 03/25/2016<br>alopez : 9/9/2013<br>tpirozzi : 9/5/2013<br>carol : 9/5/2013<br>tpirozzi : 9/5/2013<br>carol : 4/4/2013<br>ckniffin : 2/13/2013<br>carol : 9/15/2011<br>terry : 9/15/2011<br>carol : 12/10/2010<br>terry : 10/21/2009<br>wwang : 10/16/2009<br>terry : 10/15/2009<br>terry : 9/10/2008<br>alopez : 8/26/2003<br>tkritzer : 7/15/2003<br>tkritzer : 7/7/2003<br>terry : 6/30/2003<br>cwells : 12/30/2002<br>terry : 12/27/2002<br>dholmes : 3/10/1998<br>mark : 2/18/1998<br>terry : 2/12/1998<br>alopez : 6/2/1997<br>mark : 9/17/1995<br>mimadm : 12/2/1994<br>davew : 8/5/1994<br>warfield : 3/28/1994<br>supermim : 3/16/1992<br>carol : 9/4/1991
|
|
</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>
|
|
|
|
|