publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/607060

5449 lines
436 KiB
Text
Raw Permalink Blame History

<!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
- #607060 - PARKINSON DISEASE 8, AUTOSOMAL DOMINANT; PARK8
- 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=607060"><span class="mim-navbar-menu-font"> Contact Us </span></a>
</li>
<li>
<a href="/mimmatch/">
<span class="mim-navbar-menu-font">
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
MIMmatch
</span>
</span>
</a>
</li>
<li class="dropdown">
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
<li>
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
</li>
<li>
<a href="/donors"> Donors </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
<li>
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/search"> Search Help </a>
</li>
<li>
<a href="/help/linking"> Linking Help </a>
</li>
<li>
<a href="/help/api"> API Help </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/external"> External Links </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/agreement"> Use Agreement </a>
</li>
<li>
<a href="/help/copyright"> Copyright </a>
</li>
</ul>
</li>
<li>
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
</li>
</ul>
</div>
</div>
</nav>
</div>
<div id="mimSearch" class="hidden-print">
<div class="container">
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
<input type="hidden" id="mimSearchStart" name="start" value="1" />
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
<div class="row">
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
<div class="form-group">
<div class="input-group">
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
<div class="input-group-btn">
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
<ul class="dropdown-menu dropdown-menu-right">
<li class="dropdown-header">
Advanced Search
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/entry"> OMIM </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/geneMap"> Gene Map </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/history"> Search History </a>
</li>
</ul>
</div>
</div>
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
</div>
</div>
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
<span class="small">
</span>
</div>
</div>
</form>
<div class="row">
<p />
</div>
</div>
</div>
<!-- <div id="mimSearch"> -->
<div id="mimContent">
<div class="container hidden-print">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<div id="mimAlertBanner">
</div>
</div>
</div>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
<div id="mimFloatingTocMenu" class="small" role="navigation">
<p>
<span class="h4">#607060</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/607060"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="/phenotypicSeries/PS168600"> <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="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#otherFeatures">Other Features</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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;">&#9660;</div>
&nbsp;
<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;">&#9660;</div>
&nbsp;
<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=PARKINSON DISEASE 8, 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="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=23022&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="#mimGeneReviewsFold" id="mimGeneReviewsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling."><span id="mimGeneReviewsToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Gene Reviews</div>
<div id="mimGeneReviewsFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK1208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">LRRK2 Parkinson Disease</a></div><div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK1223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Parkinson Disease Overview</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607060[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=411602" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
</div>
</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;">&#9658;</div>
&nbsp;
<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:0060371" 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/607060" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA002379/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
</div>
</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.">
&nbsp;
</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> 411602<br />
<strong>DO:</strong> 0060371<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>
607060
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
PARKINSON DISEASE 8, AUTOSOMAL DOMINANT; PARK8
</span>
</h3>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/290?start=-3&limit=10&highlight=290">
12q12
</a>
</span>
</td>
<td>
<span class="mim-font">
{Parkinson disease 8}
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607060"> 607060 </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">
LRRK2
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609007"> 609007 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/607060" 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>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS168600" 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>
&nbsp;
<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/607060" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/607060" 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> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hyposmia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83156004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83156004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2364082&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2364082</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004409</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004409</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Parkinsonism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32798002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32798002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G20.C" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G20.C</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001300</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001300</a>]</span><br /> -
Bradykinesia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399317006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399317006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0233565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0233565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002067</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002067</a>]</span><br /> -
Rigidity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700109</a>, <a href="https://bioportal.bioontology.org/search?q=C0026837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span><br /> -
Resting tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25082004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25082004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234379</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002322</a>]</span><br /> -
Postural instability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843921&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843921</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002172" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002172</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002172" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002172</a>]</span><br /> -
Cognitive decline (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386806002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386806002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0338656&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0338656</a>, <a href="https://bioportal.bioontology.org/search?q=C0234985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001268</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001268</a>]</span><br /> -
Dementia (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52448006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52448006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12348006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12348006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F03.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F03.90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F03</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/290.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/294.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">294.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011265&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011265</a>, <a href="https://bioportal.bioontology.org/search?q=C0497327&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497327</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000726</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000726</a>]</span><br /> -
Neuronal loss in the substantia nigra <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846864&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846864</a>]</span><br /> -
Gliosis in the substantia nigra <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846865&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846865</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011960" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011960</a>]</span><br /> -
Pigmentary loss in the substantia nigra <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846866&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846866</a>]</span><br /> -
Lewy bodies (not always present) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846867&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846867</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43127003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43127003</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100315</a>]</span><br /> -
Neurofibrillary MAPT (tau)-positive tangles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1969813&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1969813</a>]</span><br /> -
Favorable response to levodopa <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5442007&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5442007</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002548" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002548</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002548" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002548</a>]</span><br /> -
Secondary motor complications develop in 50% of those on levodopa therapy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846869&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846869</a>]</span><br />
</span>
</div>
</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 50 to 65 years<br /> -
Relatively benign course<br /> -
Slow progression <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 /> -
Reduced penetrance, estimated to be 15% at 60 years, 21% at 70 years, and 32% at 80 years<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 leucine-rich repeat kinase 2 gene (LRRK2, <a href="/entry/609007#0001">609007.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;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>
Parkinson disease
- <a href="/phenotypicSeries/PS168600">PS168600</a>
- 34 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/1/115?start=-3&limit=10&highlight=115"> 1p36.23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606324"> Parkinson disease 7, autosomal recessive early-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606324"> 606324 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602533"> DJ1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602533"> 602533 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/208?start=-3&limit=10&highlight=208"> 1p36.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606693"> Kufor-Rakeb syndrome </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606693"> 606693 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610513"> ATP13A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610513"> 610513 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/244?start=-3&limit=10&highlight=244"> 1p36.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605909"> Parkinson disease 6, early onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605909"> 605909 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608309"> PINK1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608309"> 608309 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/601?start=-3&limit=10&highlight=601"> 1p32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606852"> {Parkinson disease 10} </a>
</span>
</td>
<td>
<span class="mim-font">
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606852"> 606852 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606852"> PARK10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606852"> 606852 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/688?start=-3&limit=10&highlight=688"> 1p31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615528"> Parkinson disease 19a, juvenile-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615528"> 615528 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608375"> DNAJC6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608375"> 608375 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/688?start=-3&limit=10&highlight=688"> 1p31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615528"> Parkinson disease 19b, early-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615528"> 615528 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608375"> DNAJC6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608375"> 608375 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1217?start=-3&limit=10&highlight=1217"> 1q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, late-onset, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606463"> GBA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606463"> 606463 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1546?start=-3&limit=10&highlight=1546"> 1q32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613164"> {Parkinson disease 16} </a>
</span>
</td>
<td>
<span class="mim-font">
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613164"> 613164 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613164"> PARK16 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613164"> 613164 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/314?start=-3&limit=10&highlight=314"> 2p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602404"> {Parkinson disease 3} </a>
</span>
</td>
<td>
<span class="mim-font">
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602404"> 602404 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602404"> PARK3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602404"> 602404 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/389?start=-3&limit=10&highlight=389"> 2p13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610297"> {Parkinson disease 13} </a>
</span>
</td>
<td>
<span class="mim-font">
</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/610297"> 610297 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606441"> HTRA2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606441"> 606441 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/1118?start=-3&limit=10&highlight=1118"> 2q37.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607688"> {Parkinson disease 11} </a>
</span>
</td>
<td>
<span class="mim-font">
</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/607688"> 607688 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612003"> GIGYF2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612003"> 612003 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/668?start=-3&limit=10&highlight=668"> 3q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616361"> Parkinson disease 21 </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="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616361"> 616361 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616361"> PARK21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616361"> 616361 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/917?start=-3&limit=10&highlight=917"> 3q27.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614251"> {Parkinson disease 18} </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/614251"> 614251 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600495"> EIF4G1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600495"> 600495 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/174?start=-3&limit=10&highlight=174"> 4p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613643"> {?Parkinson disease 5, susceptibility to} </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/613643"> 613643 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191342"> UCHL1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191342"> 191342 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/411?start=-3&limit=10&highlight=411"> 4q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168601"> Parkinson disease 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/168601"> 168601 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/163890"> SNCA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/163890"> 163890 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/411?start=-3&limit=10&highlight=411"> 4q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605543"> Parkinson disease 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/605543"> 605543 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/163890"> SNCA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/163890"> 163890 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/432?start=-3&limit=10&highlight=432"> 4q23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/103730"> ADH1C </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/103730"> 103730 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/929?start=-3&limit=10&highlight=929"> 6q24.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620923"> {Parkinson disease 26, autosomal dominant, susceptibility to} </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/620923"> 620923 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612906"> RAB32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612906"> 612906 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/1011?start=-3&limit=10&highlight=1011"> 6q26 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600116"> Parkinson disease, juvenile, type 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600116"> 600116 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602544"> PRKN </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602544"> 602544 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/1041?start=-3&limit=10&highlight=1041"> 6q27 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600075"> TBP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600075"> 600075 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/284?start=-3&limit=10&highlight=284"> 7p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616710"> Parkinson disease 22, autosomal dominant </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/616710"> 616710 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616244"> CHCHD2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616244"> 616244 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/565?start=-3&limit=10&highlight=565"> 9q34.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620482"> Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620482"> 620482 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600756"> PTPA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600756"> 600756 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/283?start=-3&limit=10&highlight=283"> 10q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619491"> {Parkinson disease 24, autosomal dominant, susceptibility to} </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/619491"> 619491 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176801"> PSAP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176801"> 176801 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/290?start=-3&limit=10&highlight=290"> 12q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607060"> {Parkinson disease 8} </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/607060"> 607060 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609007"> LRRK2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609007"> 609007 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/813?start=-3&limit=10&highlight=813"> 12q24.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, late-onset, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601517"> ATXN2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601517"> 601517 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/213?start=-3&limit=10&highlight=213"> 13q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603680"> ATXN8OS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603680"> 603680 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/466?start=-3&limit=10&highlight=466"> 14q32.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, late-onset, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607047"> ATXN3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607047"> 607047 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/264?start=-3&limit=10&highlight=264"> 15q22.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616840"> Parkinson disease 23, autosomal recessive, early onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616840"> 616840 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608879"> VPS13C </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608879"> 608879 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/404?start=-3&limit=10&highlight=404"> 16q11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614203"> {Parkinson disease 17} </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/614203"> 614203 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601501"> VPS35 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601501"> 601501 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/663?start=-3&limit=10&highlight=663"> 17q21.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/168600"> {Parkinson disease, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</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/168600"> 168600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/157140"> MAPT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/157140"> 157140 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/21/62?start=-3&limit=10&highlight=62"> 21q22.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615530"> Parkinson disease 20, early-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615530"> 615530 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604297"> SYNJ1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604297"> 604297 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/204?start=-3&limit=10&highlight=204"> 22q12.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/260300"> Parkinson disease 15, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/260300"> 260300 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605648"> FBXO7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605648"> 605648 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/268?start=-3&limit=10&highlight=268"> 22q13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612953"> Parkinson disease 14, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612953"> 612953 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603604"> PLA2G6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603604"> 603604 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/445?start=-3&limit=10&highlight=445"> Xq21-q25 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300557"> {Parkinson disease 12} </a>
</span>
</td>
<td>
<span class="mim-font">
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300557"> 300557 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300557"> PARK12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300557"> 300557 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;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">&#9660;</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 &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt 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 autosomal dominant Parkinson disease-8 (PARK8) is caused by heterozygous mutation in the LRRK2 gene (<a href="/entry/609007">609007</a>), which encodes dardarin, on chromosome 12q12.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (<a href="/entry/168600">168600</a>).</p><p>Some patients with mutations in the LRRK2 gene may be classified as having Lewy body disease or Lewy body dementia (<a href="/entry/127750">127750</a>) or various forms of frontotemporal dementia (FTD; <a href="/entry/600274">600274</a>).</p><p><a href="#8" class="mim-tip-reference" title="Dachsel, J. C., Farrer, M. J. &lt;strong&gt;LRRK2 and Parkinson disease.&lt;/strong&gt; Arch. Neurol. 67: 542-547, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20457952/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20457952&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2010.79&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20457952">Dachsel and Farrer (2010)</a> provided a review of the LRRK2 gene and its role in Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20457952" 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">&#9660;</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><a href="#18" class="mim-tip-reference" title="Hasegawa, K., Kowa, H. &lt;strong&gt;Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy.&lt;/strong&gt; Europ. Neurol. 38 (suppl. 1): 39-43, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9276200/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9276200&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000113460&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9276200">Hasegawa and Kowa (1997)</a> reported a large Japanese family with autosomal dominant parkinsonism characterized by laterality of parkinsonism at onset, mean age of onset at 51 +/- 6 years, and favorable response to dopaminergic medication. Neuropathologic examination showed pure nigral degeneration without Lewy bodies or neurofibrillary tangles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9276200" 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="#40" class="mim-tip-reference" title="Wszolek, Z. K., Pfeiffer, B., Fulgham, J. R., Parisi, J. E., Thompson, B. M., Uitti, R. J., Calne, D. B., Pfeiffer, R. F. &lt;strong&gt;Western Nebraska family (family D) with autosomal dominant parkinsonism.&lt;/strong&gt; Neurology 45: 502-505, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7898705/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7898705&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.45.3.502&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7898705">Wszolek et al. (1995)</a> reported a large family from western Nebraska in which 18 members spanning 6 generations had slowly progressive parkinsonism inherited in an autosomal dominant pattern. The family's ancestors probably immigrated to the United States from England. Clinical features included bradykinesia, rigidity, resting tremor, postural instability, and favorable response to levodopa. Postmortem examination of 1 affected individual showed neuronal and pigmentary loss, gliosis, and Lewy bodies in the substantia nigra. In a follow-up report of the same family, <a href="#41" class="mim-tip-reference" title="Wszolek, Z. K., Pfeiffer, R. F., Tsuboi, Y., Uitti, R. J., McComb, R. D., Stoessl, A. J., Strongosky, A. J., Zimprich, A., Muller-Myhsok, B., Farrer, M. J., Gasser, T., Calne, D. B., Dickson, D. W. &lt;strong&gt;Autosomal dominant parkinsonism associated with variable synuclein and tau pathology.&lt;/strong&gt; Neurology 62: 1619-1622, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15136696/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15136696&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000125015.06989.db&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15136696">Wszolek et al. (2004)</a> reported 4 additional affected members. Mean age at onset for all patients was 65 years. Pathologic examination of 4 patients showed neuronal loss and gliosis in the substantia nigra in all, but variable findings, including Lewy bodies in only 2 of 4 patients and tau (MAPT; <a href="/entry/157140">157140</a>) pathology in 1 of 4, were also seen. Using PET scan to evaluate presynaptic dopaminergic integrity of the putamen in members of the family originally reported by <a href="#40" class="mim-tip-reference" title="Wszolek, Z. K., Pfeiffer, B., Fulgham, J. R., Parisi, J. E., Thompson, B. M., Uitti, R. J., Calne, D. B., Pfeiffer, R. F. &lt;strong&gt;Western Nebraska family (family D) with autosomal dominant parkinsonism.&lt;/strong&gt; Neurology 45: 502-505, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7898705/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7898705&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.45.3.502&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7898705">Wszolek et al. (1995)</a>, <a href="#27" class="mim-tip-reference" title="Nandhagopal, R., Mak, E., Schulzer, M., McKenzie, J., McCormick, S., Sossi, V., Ruth, T. J., Strongosky, A., Farrer, M. J., Wszolek, Z. K., Stoessl, A. J. &lt;strong&gt;Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study.&lt;/strong&gt; Neurology 71: 1790-1795, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19029519/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19029519&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19029519[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000335973.66333.58&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19029519">Nandhagopal et al. (2008)</a> found that 2 asymptomatic LRRK2 mutation carriers had progressive dopaminergic dysfunction affecting transport and uptake compared to 2 family members without the mutation over a 2- to 3-year span. One of the asymptomatic mutation carriers developed subtle clinical manifestations of PD by the time of the second scan. The findings suggested that PET abnormalities are present in asymptomatic carriers early in the illness. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19029519+7898705+15136696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Paisan-Ruiz, C., Jain, S., Evans, E. W., Gilks, W. P., Simon, J., van der Brug, M., Lopez de Munain, A., Aparicio, S., Martinez Gil, A., Khan, N., Johnson, J., Martinez, J. R., and 9 others. &lt;strong&gt;Cloning of the gene containing mutations that cause PARK8-linked Parkinson&#x27;s disease.&lt;/strong&gt; Neuron 44: 595-600, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15541308/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15541308&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.neuron.2004.10.023&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15541308">Paisan-Ruiz et al. (2004)</a> reported 4 families from the Basque region of Spain and 1 family from the United Kingdom with autosomal dominant Parkinson disease. Mean age at onset was 65 years, followed by a benign course with excellent response to low doses of L-DOPA. The majority of patients presented with unilateral leg or hand tremor. No cognitive decline was noted in any of the patients even after long disease duration. <a href="#32" class="mim-tip-reference" title="Paisan-Ruiz, C., Saenz, A., Lopez de Munain, A., Marti, I., Martinez Gil, A., Marti-Masso, J. F., Perez-Tur, J. &lt;strong&gt;Familial Parkinson&#x27;s disease: clinical and genetic analysis of four Basque families.&lt;/strong&gt; Ann. Neurol. 57: 365-372, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15732106/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15732106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20391&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15732106">Paisan-Ruiz et al. (2005)</a> reported that PET scan of 1 of the Basque patients showed nigrostriatal dysfunction with a typical pattern of idiopathic presynaptic Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15541308+15732106" 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>Pathologic Findings</em></strong></p><p>
The neuropathologic findings in patients with LRRK2 mutations are pleomorphic. The most common findings include classic alpha-synuclein (SNCA; <a href="/entry/163890">163890</a>)- positive Lewy bodies and Lewy neurites, but these are not always present. Other less common findings include tau (MAPT; <a href="/entry/157140">157140</a>)- and ubiquitin (UBB; <a href="/entry/191339">191339</a>)-immunoreactive inclusions (<a href="#44" class="mim-tip-reference" title="Zimprich, A., Muller-Myhsok, Farrer, M., Leitner, P., Sharma, M., Hulihan, M., Lockhart, P., Strongosky, A., Kachergus, J., Calne, D. B., Stoessel, J., Uitti, R. J., and 9 others. &lt;strong&gt;The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval.&lt;/strong&gt; Am. J. Hum. Genet. 74: 11-19, 2004. Note: Erratum: Am. J. Med. Genet. 75: 534 only, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14691730/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14691730&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14691730[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/380647&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14691730">Zimprich et al., 2004</a>; <a href="#15" class="mim-tip-reference" title="Giasson, B. I., Covy, J. P., Bonini, N. M., Hurtig, H. I., Farrer, M. J., Trojanowski, J. Q., Van Deerlin, V. M. &lt;strong&gt;Biochemical and pathological characterization of Lrrk2.&lt;/strong&gt; Ann. Neurol. 59: 315-322, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16437584/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16437584&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20791&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16437584">Giasson et al., 2006</a>; <a href="#34" class="mim-tip-reference" title="Ross, O. A., Toft, M., Whittle, A. J., Johnson, J. L., Papapetropoulos, S., Mash, D. C., Litvan, I., Gordon, M. F., Wszolek, Z. K., Farrer, M. J., Dickson, D. W. &lt;strong&gt;Lrrk2 and Lewy body disease.&lt;/strong&gt; Ann. Neurol. 59: 388-393, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16437559/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16437559&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20731&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16437559">Ross et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16437559+14691730+16437584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Giasson, B. I., Covy, J. P., Bonini, N. M., Hurtig, H. I., Farrer, M. J., Trojanowski, J. Q., Van Deerlin, V. M. &lt;strong&gt;Biochemical and pathological characterization of Lrrk2.&lt;/strong&gt; Ann. Neurol. 59: 315-322, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16437584/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16437584&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20791&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16437584">Giasson et al. (2006)</a> reported detailed neuropathologic findings of 3 patients with PARK8 who carried the common LRRK2 G2019S mutation (<a href="/entry/609007#0006">609007.0006</a>). All showed extensive loss of pigmented neurons in the substantia nigra and locus ceruleus. Classic Lewy bodies were identified in 2 patients, 1 of whom also showed senile plaques and neurofibrillary tangles consistent with Alzheimer disease (<a href="/entry/104300">104300</a>), which may be have been part of normal aging. The third patient, who did not show Lewy bodies, uniquely demonstrated dystrophic neurons in the substantia nigra that stained intensely for LRRK2. Similar LRRK2 inclusions were not observed in analysis of more than 40 other brains with diverse neurodegenerative diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16437584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Ross, O. A., Toft, M., Whittle, A. J., Johnson, J. L., Papapetropoulos, S., Mash, D. C., Litvan, I., Gordon, M. F., Wszolek, Z. K., Farrer, M. J., Dickson, D. W. &lt;strong&gt;Lrrk2 and Lewy body disease.&lt;/strong&gt; Ann. Neurol. 59: 388-393, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16437559/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16437559&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20731&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16437559">Ross et al. (2006)</a> reported neuropathologic findings of 8 patients with PD or Lewy body disease who carried the LRRK2 G2019S mutation. All had classic Lewy bodies with a range of distribution from the brainstem to diffuse regions of the brain, but there was no apparent correlation between Lewy body pathology and disease progression. Three patients had a family history of PD. Four patients had autonomic dysfunction, 2 had dementia with Lewy bodies, and 1 had dementia with Alzheimer disease. One healthy control individual with the G2019S mutation who died at age 68 years had no significant neuropathologic findings, consistent with reduced penetrance; another control with the G2019S mutation had concomitant Alzheimer disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16437559" 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 postmortem examination of a man with PD who carried the G2019S mutation, <a href="#33" class="mim-tip-reference" title="Rajput, A., Dickson, D. W., Robinson, C. A., Ross, O. A., Dachsel, J. C., Lincoln, S. J., Cobb, S. A., Rajput, M. L., Farrer, M. J. &lt;strong&gt;Parkinsonism, Lrrk2 G2019S, and tau neuropathology&lt;/strong&gt; Neurology 67: 1506-1508, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17060589/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17060589&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000240220.33950.0c&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17060589">Rajput et al. (2006)</a> found a medial temporal tauopathy and Alzheimer-type pathology with cortical amyloid deposits and neurofibrillary deposits in multiple deep brain regions. Lewy bodies were not observed, and there was not significant neuronal loss outside of the substantia nigra. Coimmunoprecipitation studies showed no evidence of a direct interaction between LRRK2 and MAPT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17060589" 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>Using antibodies to LRRK2 epitopes located outside the folded domains of the protein, <a href="#42" class="mim-tip-reference" title="Zhu, X., Siedlak, S. L., Smith, M. A., Perry, G., Chen, S. G. &lt;strong&gt;LRRK2 protein is a component of Lewy bodies. (Letter)&lt;/strong&gt; Ann. Neurol. 60: 617-618, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16847950/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16847950&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20928&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16847950">Zhu et al. (2006)</a> found LRRK2 immunoreactivity within Lewy bodies of patients with sporadic PD. The findings suggested that LRRK2 is a component of Lewy bodies. However, <a href="#7" class="mim-tip-reference" title="Covy, J. P., Van Deerlin, V. M., Giasson, B. I. &lt;strong&gt;Lack of evidence for Lrrk2 in alpha-synuclein pathological inclusions. (Letter)&lt;/strong&gt; Ann. Neurol. 60: 618-619, 2006."None>Covy et al. (2006)</a> concluded that LRRK2 is not present in Lewy bodies, based on their studies of various LRRK2 antibodies. <a href="#7" class="mim-tip-reference" title="Covy, J. P., Van Deerlin, V. M., Giasson, B. I. &lt;strong&gt;Lack of evidence for Lrrk2 in alpha-synuclein pathological inclusions. (Letter)&lt;/strong&gt; Ann. Neurol. 60: 618-619, 2006."None>Covy et al. (2006)</a> suggested that cross-reactivity with other proteins may occur. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16847950" 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>Clinical Variability</em></strong></p><p>
In a series of 434 cases of various neurodegenerative disorders, <a href="#5" class="mim-tip-reference" title="Chen-Plotkin, A. S., Yuan, W., Anderson, C., Wood, E. M., Hurtig, H. I., Clark, C. M., Miller, B. L., Lee, V. M.-Y., Trojanowski, J. Q., Grossman, M., Van Deerlin, V. M. &lt;strong&gt;Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations.&lt;/strong&gt; Neurology 70: 521-527, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17914064/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17914064&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.WNL.0000280574.17166.26&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17914064">Chen-Plotkin et al. (2008)</a> identified 2 unrelated patients with a clinical diagnosis of corticobasal degeneration and primary progressive aphasia, respectively, who were found to have heterozygous mutations in the LRRK2 gene. These diagnoses fall within the broad clinical category of frontotemporal dementia (FTD; <a href="/entry/600274">600274</a>). The first patient, who carried the common G2019S mutation, developed difficulties in planning, organization, and memory at age 52 years. The disorder was progressive, and she later developed apraxia and extrapyramidal features including increased tone and shuffling gait. She never developed tremor. The second patient, who had a preexisting seizure disorder, presented at age 66 years with progressive speech difficulties that developed into expressive aphasia, and cognitive impairment. She had intention tremor and mild flattening of the right nasolabial fold. Brain MRI showed cortical atrophy of the left temporal lobe. <a href="#5" class="mim-tip-reference" title="Chen-Plotkin, A. S., Yuan, W., Anderson, C., Wood, E. M., Hurtig, H. I., Clark, C. M., Miller, B. L., Lee, V. M.-Y., Trojanowski, J. Q., Grossman, M., Van Deerlin, V. M. &lt;strong&gt;Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations.&lt;/strong&gt; Neurology 70: 521-527, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17914064/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17914064&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.WNL.0000280574.17166.26&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17914064">Chen-Plotkin et al. (2008)</a> concluded that the LRRK2-associated neurodegenerative phenotype may be more heterogeneous than previously assumed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17914064" 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="pathogenesis" class="mim-anchor"></a>
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#14" class="mim-tip-reference" title="Gehrke, S., Imai, Y., Sokol, N., Lu, B. &lt;strong&gt;Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression.&lt;/strong&gt; Nature 466: 637-641, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20671708/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20671708&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20671708[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature09191&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20671708">Gehrke et al. (2010)</a> found that LRRK2 interacted with the microRNA (miRNA) pathway to regulate protein synthesis. They showed that mRNAs for Drosophila E2f1 (<a href="/entry/189971">189971</a>) and Dp (TFDP1; <a href="/entry/189902">189902</a>), which had previously been implicated in cell cycle and survival control (<a href="#17" class="mim-tip-reference" title="Girling, R., Partridge, J. F., Bandara, L. R., Burden, N., Totty, N. F., Hsuan, J. J., La Thangue, N. B. &lt;strong&gt;A new component of the transcription factor DRTF1/E2F.&lt;/strong&gt; Nature 362: 83-87, 1993. Note: Erratum: Nature 365: 468 only, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8446173/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8446173&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/362083a0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8446173">Girling et al., 1993</a>), were translationally repressed by the miRNAs Let7 (MIRLET7A1; <a href="/entry/605386">605386</a>) and miR184* (<a href="/entry/613146">613146</a>), respectively. Pathogenic human LRRK2 antagonized Let7 and miR184*, leading to overproduction of E2f1 and Dp, which was critical for LRRK2 pathogenesis. In Drosophila, genetic deletion of Let7, antagomir-mediated blockage of Let7 and miR184* action, transgenic expression of Dp target protector, or replacement of endogenous Dp with a Dp transgene nonresponsive to Let7 each had toxic effects similar to those of pathogenic LRRK2. Conversely, increasing the level of Let7 or miR184* attenuated pathogenic LRRK2 effects. Human LRRK2 associated with Drosophila Argonaute-1 (EIF2C1, or AGO1; <a href="/entry/606228">606228</a>) or human Argonaute-2 (EIF2C2, or AGO2; <a href="/entry/606229">606229</a>) of the RNA-induced silencing complex (RISC). In aged fly brain, Ago1 protein level was negatively regulated by human LRRK2. Furthermore, pathogenic LRRK2 promoted the association of phosphorylated 4EBP1 (EIF4EPB1; <a href="/entry/602223">602223</a>) with human AGO2. <a href="#14" class="mim-tip-reference" title="Gehrke, S., Imai, Y., Sokol, N., Lu, B. &lt;strong&gt;Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression.&lt;/strong&gt; Nature 466: 637-641, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20671708/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20671708&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20671708[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature09191&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20671708">Gehrke et al. (2010)</a> concluded that deregulated synthesis of E2F1 and DP caused by miRNA pathway impairment is a key event in LRRK2 pathogenesis, suggesting that novel miRNA-based therapeutic strategies may be useful for Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8446173+20671708" 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="otherFeatures" class="mim-anchor"></a>
<h4 href="#mimOtherFeaturesFold" id="mimOtherFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimOtherFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Other Features</strong>
</span>
</h4>
</div>
<div id="mimOtherFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#37" class="mim-tip-reference" title="Silveira-Moriyama, L., Guedes, L. C., Kingsbury, A., Ayling, H., Shaw, K., Barbosa, E. R., Bonifati, V., Quinn, N. P., Abou-Sleiman, P., Wood, N. W., Petrie, A., Sampaio, C., Ferreira, J. J., Holton, J., Revesz, T., Lees, A. J. &lt;strong&gt;Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data.&lt;/strong&gt; Neurology 71: 1021-1026, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18809839/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18809839&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000326575.20829.45&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18809839">Silveira-Moriyama et al. (2008)</a> found that 19 patients with PARK8 and the common G2019S mutation (<a href="/entry/609007#0006">609007.0006</a>) scored lower on a test of smell, indicating decreased olfactory function and hyposmia, compared to controls or to 2 asymptomatic G2019S carriers. Postmortem examination of the rhinencephalon in 4 PARK8 patients, only 1 of whom had been clinically tested and had hyposmia, showed alpha-synuclein accumulation in olfactory pathways. The authors commented that hyposmia has been reported in up to 80% of patients with Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18809839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Saunders-Pullman, R., Stanley, K., Wang, C., San Luciano, M., Shanker, V., Hunt, A., Severt, L., Raymond, D., Ozelius, L. J., Lipton, R. B., Bressman, S. B. &lt;strong&gt;Olfactory dysfunction in LRRK2 G2019S mutation carriers.&lt;/strong&gt; Neurology 77: 319-324, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21753159/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21753159&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e318227041c&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21753159">Saunders-Pullman et al. (2011)</a> examined olfaction in 31 individuals with G2019S-related PD, 30 with non-LRRK2 PD, 28 nonmanifesting G2019S carriers, and 46 controls. The mean score of all those with PD reflected impaired olfaction compared to controls, although G2019S-related PD patients had less severe impairment compared to non-LRRK2 PD patients. Nonmanifesting LRRK2 mutation carriers had subtle olfactory impairment that was less severe than that in manifesting mutation carriers. However, the study could not determine if the subtle olfactory deficit in nonmanifesting disease carriers could predict future development of motor symptoms, and the authors suggested that longitudinal studies were warranted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21753159" 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="#26" class="mim-tip-reference" title="Marras, C., Schule, B., Munhoz, R. P., Rogaeva, E., Langston, J. W., Kasten, M., Meaney, C., Klein, C., Wadia, P. M., Lim, S.-Y., Chuang, R. S.-I., Zadikof, C., and 10 others. &lt;strong&gt;Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers.&lt;/strong&gt; Neurology 77: 325-333, 2011. Note: Erratum: Neurology 77: 1501 only, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21753163/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21753163&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e318227042d&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21753163">Marras et al. (2011)</a> examined the clinical features of 112 individuals from 15 families with the G2019S mutation, including 25 PD-manifesting mutation carriers and 29 nonmanifesting mutation carriers (54 mutation carriers total). Among the manifesting carriers, tremor was the most commonly recognized initial symptom, and tremor, postural instability, and gait disorders were most common even in early disease. Olfaction was abnormal only in 2 of 7 with short disease duration, but was abnormal in 8 of 10 with long disease duration. Eleven of 19 manifesting patients tested showed impaired color discrimination. Compared to 84 individuals with idiopathic PD, G2019S PD patients had better olfactory sense, worse depression scores, worse color discrimination, more common tremor at presentation and gait dysfunction, and slightly better motor scores earlier in disease duration. However, the phenotypes were largely overlapping. Nonmanifesting mutation carriers had an increased frequency of tremor (31%) compared to noncarriers (12%) and to unrelated controls (13%). Nonmanifesting mutation carriers had increased constipation (12%) compared to controls (2%), as well as worse color discrimination compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21753163" 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="Aasly, J. O., Shi, M., Sossi, V., Stewart, T., Johansen, K. K., Wszolek, Z. K., Uitti, R. J., Hasegawa, K., Yokoyama, T., Zabetian, C. P., Kim, H. M., Leverenz, J. B., Ginghina, C., Armaly, J., Edwards, K. L., Snapinn, K. W., Stoessl, A. J., Zhang, J. &lt;strong&gt;Cerebrospinal fluid amyloid beta and tau in LRRK2 mutation carriers.&lt;/strong&gt; Neurology 78: 55-61, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22170881/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22170881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22170881[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e31823ed101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22170881">Aasly et al. (2012)</a> studied 26 patients with LRRK2 mutations, including 18 asymptomatic carriers and 8 patients at an early stage of PD. Symptomatic patients had reduced CSF levels of beta-amyloid-42 (APP; <a href="/entry/104760">104760</a>), total tau (MAPT; <a href="/entry/157140">157140</a>), and phosphorylated tau compared to asymptomatic mutation carriers. PET scan for 3 markers of dopaminergic function in the striatum showed significantly reduced values for all 3 markers in all symptomatic mutation carriers, whereas only 4 asymptomatic mutations carriers had reduction of all 3 tracers studied. There was a trend towards a correlation between decreased striatal dopaminergic function and reduced CSF beta-amyloid-42 and tau levels, with significant values only for beta-amyloid-42 and fluorodopa uptake. When cases were restricted to those with the G2019S mutation, significant correlations were also observed for tau. The findings suggested a link between beta-amyloid and tau deposition and the pathogenesis of LRRK2-related PD. However, <a href="#1" class="mim-tip-reference" title="Aasly, J. O., Shi, M., Sossi, V., Stewart, T., Johansen, K. K., Wszolek, Z. K., Uitti, R. J., Hasegawa, K., Yokoyama, T., Zabetian, C. P., Kim, H. M., Leverenz, J. B., Ginghina, C., Armaly, J., Edwards, K. L., Snapinn, K. W., Stoessl, A. J., Zhang, J. &lt;strong&gt;Cerebrospinal fluid amyloid beta and tau in LRRK2 mutation carriers.&lt;/strong&gt; Neurology 78: 55-61, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22170881/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22170881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22170881[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e31823ed101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22170881">Aasly et al. (2012)</a> noted that this was an exploratory study, that the data should be interpreted with caution, and that the results need to be replicated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22170881" 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 cross-sectional study of 490 Jewish patients with PD, <a href="#19" class="mim-tip-reference" title="Inzelberg, R., Cohen, O. S., Aharon-Peretz, J., Schlesinger, I., Gershoni-Baruch, R., Djaldetti, R., Nitsan, Z., Ephraty, L., Tunkel, O., Kozlova, E., Inzelberg, L., Kaplan, N., Fixler Mehr, T., Mory, A., Dagan, E., Schechtman, E., Friedman, E., Hassin-Baer, S. &lt;strong&gt;The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers.&lt;/strong&gt; Neurology 78: 781-786, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22323743/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22323743&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e318249f673&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22323743">Inzelberg et al. (2012)</a> found that 79 (16.1%) carried the common G2019S mutation. Eighteen (23%) G2019S mutation carriers had a non-skin cancer compared to 49 (12%) nonmutation carriers (odds ratio = 2.18). A significant ethnicity effect was noted for those of Ashkenazi Jewish ancestry: the age-adjusted odds ratio for the development of non-skin cancer among Ashkenazi Jewish carriers of the G2019S mutation was 3.38. The most common cancer was breast, which accounted for 15% of the cancer types. The LRRK2 G2019S causes a gain of function for the kinase, which could potentially play a role in tumorigenesis. However, <a href="#4" class="mim-tip-reference" title="Bandmann, O., Cookson, M. R. &lt;strong&gt;Parkinson disease, cancer, and LRRK2: causation or association?&lt;/strong&gt; Neurology 78: 772-773, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22323745/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22323745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e318249f744&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22323745">Bandmann and Cookson (2012)</a> noted that the study showed an association between G2019S and non-skin cancer, but did not prove causation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22323745+22323743" 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">&#9660;</span>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#11" class="mim-tip-reference" title="Funayama, M., Hasegawa, K., Kowa, H., Saito, M., Tsuji, S., Obata, F. &lt;strong&gt;A new locus for Parkinson&#x27;s disease (PARK8) maps to chromosome 12p11.2-q13.1.&lt;/strong&gt; Ann. Neurol. 51: 296-301, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11891824/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11891824&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.10113&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11891824">Funayama et al. (2002)</a> performed a genomewide linkage analysis in the family reported by <a href="#18" class="mim-tip-reference" title="Hasegawa, K., Kowa, H. &lt;strong&gt;Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy.&lt;/strong&gt; Europ. Neurol. 38 (suppl. 1): 39-43, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9276200/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9276200&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000113460&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9276200">Hasegawa and Kowa (1997)</a>. Allele typing was performed for 31 individuals from 4 generations. Parametric 2-point linkage analysis yielded a maximum lod score of 4.32 at D12S345 (12p11.2). Parametric multipoint linkage analysis of the 13.6-cM interval around this marker yielded lod scores greater than 4.0 at D12S85 (12q12). Haplotype analysis showed 2 recombination events which further defined the candidate region. The haplotype was shared by 15 affected individuals and by 8 unaffected individuals, which raised the possibility of incomplete penetrance. Nonparametric linkage analysis also supported mapping of the parkinsonism locus to 12p11.2-q13.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9276200+11891824" 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 21 Caucasian families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission, <a href="#44" class="mim-tip-reference" title="Zimprich, A., Muller-Myhsok, Farrer, M., Leitner, P., Sharma, M., Hulihan, M., Lockhart, P., Strongosky, A., Kachergus, J., Calne, D. B., Stoessel, J., Uitti, R. J., and 9 others. &lt;strong&gt;The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval.&lt;/strong&gt; Am. J. Hum. Genet. 74: 11-19, 2004. Note: Erratum: Am. J. Med. Genet. 75: 534 only, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14691730/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14691730&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14691730[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/380647&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14691730">Zimprich et al. (2004)</a> tested for linkage to the PARK8 region. Two families, one a German Canadian family and the other a family from western Nebraska (<a href="#40" class="mim-tip-reference" title="Wszolek, Z. K., Pfeiffer, B., Fulgham, J. R., Parisi, J. E., Thompson, B. M., Uitti, R. J., Calne, D. B., Pfeiffer, R. F. &lt;strong&gt;Western Nebraska family (family D) with autosomal dominant parkinsonism.&lt;/strong&gt; Neurology 45: 502-505, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7898705/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7898705&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.45.3.502&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7898705">Wszolek et al., 1995</a>), reached significant linkage on their own, with a combined maximum multipoint lod score of 3.33. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14691730+7898705" 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 genomewide association study and 2 replication studies in a total of 2,011 cases and 18,381 controls from Japan, <a href="#35" class="mim-tip-reference" title="Satake, W., Nakabayashi, Y., Mizuta, I., Hirota, Y., Ito, C., Kubo, M., Kawaguchi, T., Tsunoda, T., Watanabe, M., Takeda, A., Tomiyama, H., Nakashima, K., and 10 others. &lt;strong&gt;Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson&#x27;s disease. (Letter)&lt;/strong&gt; Nature Genet. 41: 1303-1307, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19915576/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19915576&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.485&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19915576">Satake et al. (2009)</a> found strong association with the LRRK2 gene (<a href="/entry/609007">609007</a>) on 12q12 (p = 2.72 x 10(-8)), implicated in PARK8. <a href="#39" class="mim-tip-reference" title="Tan, E.-K., Kwok, H.-H., Tan, L. C., Zhao, W.-T., Prakash, K. M., Au, W.-L., Pavanni, R., Ng, Y.-Y., Satake, W., Zhao, Y., Toda, T., Liu, J.-J. &lt;strong&gt;Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus.&lt;/strong&gt; Neurology 75: 508-512, 2010. Note: Erratum: Neurology 75: 1399 only, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20697102/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20697102&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181eccfcd&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20697102">Tan et al. (2010)</a> specifically analyzed 3 SNPs at the PARK8 locus in 433 PD patients and 916 controls, all of Chinese ethnicity, and independently confirmed a significant association with PARK8. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19915576+20697102" 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">&#9660;</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 Basque families and 1 English family with autosomal dominant PD, <a href="#30" class="mim-tip-reference" title="Paisan-Ruiz, C., Jain, S., Evans, E. W., Gilks, W. P., Simon, J., van der Brug, M., Lopez de Munain, A., Aparicio, S., Martinez Gil, A., Khan, N., Johnson, J., Martinez, J. R., and 9 others. &lt;strong&gt;Cloning of the gene containing mutations that cause PARK8-linked Parkinson&#x27;s disease.&lt;/strong&gt; Neuron 44: 595-600, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15541308/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15541308&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.neuron.2004.10.023&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15541308">Paisan-Ruiz et al. (2004)</a> identified 2 different heterozygous mutations in the LRRK2 gene (<a href="/entry/609007#0001">609007.0001</a> and <a href="/entry/609007#0002">609007.0002</a>, respectively). The disease showed 100% penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15541308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a Nebraskan kindred with autosomal dominant PD originally reported by <a href="#40" class="mim-tip-reference" title="Wszolek, Z. K., Pfeiffer, B., Fulgham, J. R., Parisi, J. E., Thompson, B. M., Uitti, R. J., Calne, D. B., Pfeiffer, R. F. &lt;strong&gt;Western Nebraska family (family D) with autosomal dominant parkinsonism.&lt;/strong&gt; Neurology 45: 502-505, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7898705/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7898705&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.45.3.502&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7898705">Wszolek et al. (1995)</a>, <a href="#43" class="mim-tip-reference" title="Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R. J., Calne, D. B., Stoessl, A. J., Pfeiffer, R. F., Patenge, N., Carballo Carbajal, I., Vieregge, P., Asmus, F., Muller-Myhsok, B., Dickson, D. W., Meitinger, T., Strom, T. M., Wszolek, Z. K., Gasser, T. &lt;strong&gt;Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.&lt;/strong&gt; Neuron 44: 601-607, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15541309/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15541309&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.neuron.2004.11.005&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15541309">Zimprich et al. (2004)</a> identified a heterozygous mutation in the LRRK2 gene (<a href="/entry/609007#0003">609007.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7898705+15541309" 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 of 61 (6.6%) families with autosomal dominant PD, <a href="#9" class="mim-tip-reference" title="Di Fonzo, A., Rohe, C. F., Ferreira, J., Chien, H. F., Vacca, L., Stocchi, F., Guedes, L., Fabrizio, E., Manfredi, M., Vanacore, N., Goldwurm, S., Breedveld, G., Sampaio, C., Meco, G., Barbosa, E., Oostra, B. A., Bonifati, V., Italian Parkinson Genetics Network. &lt;strong&gt;A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson&#x27;s disease.&lt;/strong&gt; Lancet 365: 412-415, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15680456/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15680456&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(05)17829-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15680456">Di Fonzo et al. (2005)</a> identified a heterozygous gly2019-to-ser (G2019S; <a href="/entry/609007#0006">609007.0006</a>) mutation in the LRRK2 gene. Two families were from Italy, and 1 each were from Portugal and Brazil. <a href="#16" class="mim-tip-reference" title="Gilks, W. P., Abou-Sleiman, P. M., Gandhi, S., Jain, S., Singleton, A., Lees, A. J., Shaw, K., Bhatia, K. P., Bonifati, V., Quinn, N. P., Lynch, J., Healy, D. G., Holton, J. L., Revesz, T., Wood, N. W. &lt;strong&gt;A common LRRK2 mutation in idiopathic Parkinson&#x27;s disease.&lt;/strong&gt; Lancet 365: 415-416, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15680457/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15680457&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(05)17830-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15680457">Gilks et al. (2005)</a> identified the G2019S mutation in 8 of 482 (1.6%) unrelated patients with Parkinson disease. Five of the patients had no family history of the disorder, suggesting either a de novo occurrence or reduced penetrance. <a href="#28" class="mim-tip-reference" title="Nichols, W. C., Pankratz, N., Hernandez, D., Paisan-Ruiz, C., Jain, S., Halter, C. A., Michaels, V. E., Reed, T., Rudolph, A., Shults, C. W., Singleton, A., Foroud, T. &lt;strong&gt;Genetic screening for a single common LRRK2 mutation in familial Parkinson&#x27;s disease.&lt;/strong&gt; Lancet 365: 410-412, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15680455/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15680455&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(05)17828-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15680455">Nichols et al. (2005)</a> identified the G2019S mutation in 20 of 358 (6%) families with PD. In 1 family, 1 sib was heterozygous for the mutation and another was homozygous; the homozygous individual did not differ in clinical presentation from the sib and did not have early disease onset or more rapid progression. <a href="#28" class="mim-tip-reference" title="Nichols, W. C., Pankratz, N., Hernandez, D., Paisan-Ruiz, C., Jain, S., Halter, C. A., Michaels, V. E., Reed, T., Rudolph, A., Shults, C. W., Singleton, A., Foroud, T. &lt;strong&gt;Genetic screening for a single common LRRK2 mutation in familial Parkinson&#x27;s disease.&lt;/strong&gt; Lancet 365: 410-412, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15680455/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15680455&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(05)17828-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15680455">Nichols et al. (2005)</a> suggested genetic screening for the G2019S mutation in patients with familial PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15680456+15680457+15680455" 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 all 19 affected members of the original Japanese family with PARK8 (<a href="#18" class="mim-tip-reference" title="Hasegawa, K., Kowa, H. &lt;strong&gt;Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy.&lt;/strong&gt; Europ. Neurol. 38 (suppl. 1): 39-43, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9276200/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9276200&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000113460&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9276200">Hasegawa and Kowa, 1997</a>), <a href="#12" class="mim-tip-reference" title="Funayama, M., Hasegawa, K., Ohta, E., Kawashima, N., Komiyama, M., Kowa, H., Tsuji, S., Obata, F. &lt;strong&gt;An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.&lt;/strong&gt; Ann. Neurol. 57: 918-921, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15880653/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15880653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20484&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15880653">Funayama et al. (2005)</a> identified a heterozygous mutation in the LRRK2 gene (<a href="/entry/609007#0007">609007.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9276200+15880653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Farrer, M., Stone, J., Mata, I. F., Lincoln, S., Kachergus, J., Hulihan, M., Strain, K. J., Maraganore, D. M. &lt;strong&gt;LRRK2 mutations in Parkinson disease.&lt;/strong&gt; Neurology 65: 738-740, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16157908/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16157908&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000169023.51764.b0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16157908">Farrer et al. (2005)</a> identified pathogenic mutations in the LRRK2 gene in 5 (0.6%) of 786 probands with idiopathic Parkinson disease. Four probands carried the common G2019S mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16157908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Paisan-Ruiz, C., Lang, A. E., Kawarai, T., Sato, C., Salehi-Rad, S., Fisman, G. K., Al-Khairallah, T., St George-Hyslop, P., Singleton, A., Rogaeva, E. &lt;strong&gt;LRRK2 gene in Parkinson disease: mutation analysis and case control association study.&lt;/strong&gt; Neurology 65: 696-700, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16157901/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16157901&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000167552.79769.b3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16157901">Paisan-Ruiz et al. (2005)</a> identified 2 different LRRK2 mutations in 3 of 23 unrelated probands with autosomal dominant Parkinson disease. Two probands had the common G2019S mutation. In a case-control study of 121 unrelated Parkinson disease patients and 250 controls, <a href="#31" class="mim-tip-reference" title="Paisan-Ruiz, C., Lang, A. E., Kawarai, T., Sato, C., Salehi-Rad, S., Fisman, G. K., Al-Khairallah, T., St George-Hyslop, P., Singleton, A., Rogaeva, E. &lt;strong&gt;LRRK2 gene in Parkinson disease: mutation analysis and case control association study.&lt;/strong&gt; Neurology 65: 696-700, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16157901/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16157901&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000167552.79769.b3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16157901">Paisan-Ruiz et al. (2005)</a> found no association between PD and any of 4 LRRK2 polymorphisms examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16157901" 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="Ishihara, L., Warren, L., Gibson, R., Amouri, R., Lesage, S., Durr, A., Tazir, M., Wszolek, Z. K., Uitti, R. J., Nichols, W. C., Griffith, A., Hattori, N., Leppert, D., Watts, R., Zabetian, C. P., Foroud, T. M., Farrer, M. J., Brice, A., Middleton, L., Hentati, F. &lt;strong&gt;Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations.&lt;/strong&gt; Arch. Neurol. 63: 1250-1254, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16966502/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16966502&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.63.9.1250&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16966502">Ishihara et al. (2006)</a> found no observable phenotypic differences between 26 patients with Parkinson disease who were homozygous for the G2019S mutation, including 20 patients of Tunisian origin, and reports of patients who were heterozygous for the mutation. In addition, 3 clinically unaffected Tunisian individuals were homozygous for the mutation at ages 42, 45, and 70 years. The findings did not support a gene dosage effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16966502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Alcalay, R. N., Caccappolo, E., Mejia-Santana, H., Tang, M. X., Rosado, L., Ross, B. M., Verbitsky, M., Kisselev, S., Louis, E. D., Comella, C., Colcher, A., Jennings, D., and 21 others. &lt;strong&gt;Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the Consortium on Risk for Early Onset Parkinson Disease study.&lt;/strong&gt; Arch. Neurol. 67: 1116-1122, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20837857/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20837857&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2010.194&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20837857">Alcalay et al. (2010)</a> identified the G2019S mutation in 35 (3.6%) of 953 patients with early-onset PD before age 51, including 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Four of the 35 patients had the G2019S mutation and another mutation in the PRKN (PARK2; <a href="/entry/602544">602544</a>) or GBA genes (<a href="/entry/606463">606463</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20837857" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#3" class="mim-tip-reference" title="Alcalay, R. N., Mejia-Santana, H., Tang, M. X., Rosado, L., Verbitsky, M., Kisselev, S., Ross, B. M., Louis, E. D., Comella, C. L., Colcher, A., Jennings, D., Nance, M. A., and 21 others. &lt;strong&gt;Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease.&lt;/strong&gt; Arch. Neurol. 66: 1517-1522, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20008657/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20008657&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2009.267&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20008657">Alcalay et al. (2009)</a> found that 34 (3.7%) of 925 patients with early-onset PD, defined as age at onset before age 51 years, carried the G2019S mutation. Compared to noncarriers, carriers of the G2019S mutation were more likely to be of Ashkenazi Jewish descent (55.9% vs 11.9%), to have a lower tremor score (p = 0.03), and to have a higher score of postural instability and gait difficulty (PIGD; 92.3% vs 58.9%, p = 0.003). The PIGD phenotype in general is associated with a more severe phenotype and a faster rate of cognitive decline compared to the tremor dominant phenotype, so the findings of this study suggested implications for disease course in G2019S mutation carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20008657" 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>Mutations in the LRRK2 gene and the GBA gene commonly predispose to PD in individuals of Ashkenazi Jewish descent. <a href="#13" class="mim-tip-reference" title="Gan-Or, Z., Bar-Shira, A., Mirelman, A., Gurevich, T., Kedmi, M., Giladi, N., Orr-Urtreger, A. &lt;strong&gt;LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease.&lt;/strong&gt; Neurogenetics 11: 121-125, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19458969/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19458969&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-009-0198-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19458969">Gan-Or et al. (2010)</a> screened a cohort of 600 Ashkenazi PD patients for the common LRRK2 G2019S mutation and for 8 GBA mutations. Among all patients, 117 (19.5%) were heterozygous for GBA mutations, and 82 (13.7%) were heterozygous for the LRRK2 G2019S mutation, including 8 patients carrying both GBA and LRRK2 mutations. There were 6 (1.0%) homozygotes or compound heterozygotes GBA mutations carriers, and 1 (0.2%) patient homozygote for G2019S. Carriers of LRRK2 G2019S or GBA mutations had a significantly earlier average age at onset (57.5 and 57.5 years) than noncarriers (61.0 years); the 8 with mutations in both genes had a similar average age at onset (57.4 years). A phenotypic comparison of those with the G2019S mutation, GBA mutations, and noncarriers of these mutations showed that more of those with the G2019S mutation reported muscle stiffness/rigidity (p = 0.007) and balance disturbances (p = 0.008), while more GBA mutation carriers reported slowness/bradykinesia (p = 0.021). However, the most common presenting symptom in both groups was tremor (about 50%). These results suggested distinct effects of LRRK2 or GBA mutations on the initial symptoms of PD in some cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19458969" 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">&#9660;</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><a href="#29" class="mim-tip-reference" title="Orr-Urtreger, A., Shifrin, C., Rozovski, U., Rosner, S., Bercovich, D., Gurevich, T., Yagev-More, H., Bar-Shira, A., Giladi, N. &lt;strong&gt;The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect?&lt;/strong&gt; Neurology 69: 1595-1602, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17938369/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17938369&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000277637.33328.d8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17938369">Orr-Urtreger et al. (2007)</a> identified a heterozygous G2019S mutation in 12.3% of 472 Jewish PD patients, and in 14.8% of the 344 patients in this group who were specifically of Ashkenazi Jewish origin. The mutation was also detected in 2.4% of Ashkenazi Jewish controls. A common shared haplotype identified by <a href="#24" class="mim-tip-reference" title="Lesage, S., Leutenegger, A.-L., Ibanez, P., Janin, S., Lohmann, E., Durr, A., Brice, A. &lt;strong&gt;LRRK2 haplotype analysis in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 77: 330-332, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16145815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16145815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/432422&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16145815">Lesage et al. (2005)</a> was found in 97% of mutation carriers. None of 42 Jewish patients from Iraq or Morocco carried the G2019S mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17938369+16145815" 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="#38" class="mim-tip-reference" title="Skipper, L., Li, Y., Bonnard, C., Pavanni, R., Yih, Y., Chua, E., Sung, W.-K., Tan, L., Wong, M.-C., Tan, E.-K., Liu, J. &lt;strong&gt;Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson&#x27;s disease.&lt;/strong&gt; Hum. Molec. Genet. 14: 3549-3556, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16269443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16269443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddi376&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16269443">Skipper et al. (2005)</a> identified a subset of tagging-SNPs (tSNP) that captured the majority of common variation within the LRRK2. Both single tSNP and tSNP haplotype analyses, using a large epidemiologically-matched sporadic case-control series comprising 932 Chinese individuals, yielded significant evidence for association with Parkinson disease. The authors identified a haplotype that dramatically increased disease risk when present in 2 copies (odds ratio = 5.5; P = 0.0001). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16269443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Choi, J. M., Woo, M. S., Ma, H.-I., Kang, S. Y., Sung, Y.-H., Yong, S. W., Chung, S. J., Kim, J.-S., Shin, H., Lyoo, C. H., Lee, P. H., Baik, J. S., and 9 others. &lt;strong&gt;Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.&lt;/strong&gt; Neurogenetics 9: 263-269, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18704525/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18704525&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-008-0138-0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18704525">Choi et al. (2008)</a> did not identify the G2019S mutation in 72 unrelated Korean patients with onset of PD before age 50, suggesting that it is not a common cause of PD in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18704525" 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="#22" class="mim-tip-reference" title="Lesage, S., Belarbi, S., Troiano, A., Condroyer, C., Hecham, N., Pollak, P., Lohman, E., Benhassine, T., Ysmail-Dahlouk, F., Durr, A., Tazir, M., Brice, A. &lt;strong&gt;Is the common LRRK2 G2019S mutation related to dyskinesias in North African Parkinson disease?&lt;/strong&gt; Neurology 71: 1550-1552, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18981379/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18981379&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000338460.89796.06&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18981379">Lesage et al. (2008)</a> identified the G2019S mutation in 7 (41%) of 17 North African patients with familial PD and 40 (34%) of 119 North African patients with sporadic PD. All were heterozygous for the mutation except 3 patients, who were homozygous. One (1.5%) of 66 Algerian controls was homozygous for the mutation, but showed no evidence of disease at age 41 years, which is younger than the average age of disease onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18981379" 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="#23" class="mim-tip-reference" title="Lesage, S., Condroyer, C., Lannuzel, A., Lohmann, E., Troiano, A., Tison, F., Damier, P., Thobois, S., Ouvrard-Hernandez, A.-M., Rivaud-Pechoux, S., Brefel-Courbon, C., Destee, A., Tranchant, C., Romana, M., Leclere, L., Durr, A., Brice, A. &lt;strong&gt;Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson&#x27;s disease. (Letter)&lt;/strong&gt; J. Med. Genet. 46: 458-464, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19357115/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19357115&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2008.062612&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19357115">Lesage et al. (2009)</a> found 8 potentially or proven pathogenic mutations, including 4 novel mutations, in the LRRK2 gene in 22 (9.7%) of 226 probands with autosomal dominant Parkinson disease, including 182 from France and 14 from North Africa. The common G2019S mutation was identified in 13 (5.8%) probands, including 6 (43%) from North Africa. Heterozygous mutations R1441H (<a href="/entry/609007#0008">609007.0008</a>) and I1371V were found in 2 probands each. Most of the mutations were located in the functional domains of the LRRK2 protein. Some of the patients had been previously reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19357115" 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">&#9660;</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="#25" class="mim-tip-reference" title="Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., Ren, Q., Jiao, Y., Sawa, A., Moran, T., Ross, C. A., Montell, C., Smith, W. W. &lt;strong&gt;A Drosophila model for LRRK2-linked parkinsonism.&lt;/strong&gt; Proc. Nat. Acad. Sci. 105: 2693-2698, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18258746/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18258746&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18258746[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0708452105&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18258746">Liu et al. (2008)</a> found that Drosophila expressing the human LRRK2 G2019S mutation in neuronal cells showed adult-onset loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Overexpression of LRRK2 resulted in a less severe form of parkinsonism. Treatment of mutant flies with L-DOPA improved locomotor impairment but did not prevent loss of dopaminergic cells. Expression of mutant protein in photoreceptor cells resulted in retinal degeneration. The findings provided a gain-of-function animal model for human LRRK2-linked PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18258746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Lee, B. D., Shin, J.-H., VanKampen, J., Petrucelli, L., West, A. B., Ko, H. S., Lee, Y.-I., Maguire-Zeiss, K. A., Bowers, W. J., Federoff, H. J., Dawson, V. L., Dawson, T. M. &lt;strong&gt;Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson&#x27;s disease.&lt;/strong&gt; Nature Med. 16: 998-1000, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20729864/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20729864&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20729864[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nm.2199&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20729864">Lee et al. (2010)</a> presented evidence demonstrating that pharmacologic inhibitors of LRRK2 kinase activity are protective in both in vitro and in vivo mouse models of LRRK2-induced neurodegeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20729864" 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">&#9660;</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="Aasly2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Aasly, J. O., Shi, M., Sossi, V., Stewart, T., Johansen, K. K., Wszolek, Z. K., Uitti, R. J., Hasegawa, K., Yokoyama, T., Zabetian, C. P., Kim, H. M., Leverenz, J. B., Ginghina, C., Armaly, J., Edwards, K. L., Snapinn, K. W., Stoessl, A. J., Zhang, J.
<strong>Cerebrospinal fluid amyloid beta and tau in LRRK2 mutation carriers.</strong>
Neurology 78: 55-61, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22170881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22170881</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22170881[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=22170881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e31823ed101" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Alcalay2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Alcalay, R. N., Caccappolo, E., Mejia-Santana, H., Tang, M. X., Rosado, L., Ross, B. M., Verbitsky, M., Kisselev, S., Louis, E. D., Comella, C., Colcher, A., Jennings, D., and 21 others.
<strong>Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the Consortium on Risk for Early Onset Parkinson Disease study.</strong>
Arch. Neurol. 67: 1116-1122, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20837857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20837857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20837857" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneurol.2010.194" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Alcalay2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Alcalay, R. N., Mejia-Santana, H., Tang, M. X., Rosado, L., Verbitsky, M., Kisselev, S., Ross, B. M., Louis, E. D., Comella, C. L., Colcher, A., Jennings, D., Nance, M. A., and 21 others.
<strong>Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease.</strong>
Arch. Neurol. 66: 1517-1522, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20008657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20008657</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20008657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneurol.2009.267" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Bandmann2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bandmann, O., Cookson, M. R.
<strong>Parkinson disease, cancer, and LRRK2: causation or association?</strong>
Neurology 78: 772-773, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22323745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e318249f744" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Chen-Plotkin2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chen-Plotkin, A. S., Yuan, W., Anderson, C., Wood, E. M., Hurtig, H. I., Clark, C. M., Miller, B. L., Lee, V. M.-Y., Trojanowski, J. Q., Grossman, M., Van Deerlin, V. M.
<strong>Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations.</strong>
Neurology 70: 521-527, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17914064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17914064</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17914064" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.WNL.0000280574.17166.26" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Choi2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Choi, J. M., Woo, M. S., Ma, H.-I., Kang, S. Y., Sung, Y.-H., Yong, S. W., Chung, S. J., Kim, J.-S., Shin, H., Lyoo, C. H., Lee, P. H., Baik, J. S., and 9 others.
<strong>Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.</strong>
Neurogenetics 9: 263-269, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18704525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18704525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18704525" 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/s10048-008-0138-0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Covy2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Covy, J. P., Van Deerlin, V. M., Giasson, B. I.
<strong>Lack of evidence for Lrrk2 in alpha-synuclein pathological inclusions. (Letter)</strong>
Ann. Neurol. 60: 618-619, 2006.
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Dachsel2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dachsel, J. C., Farrer, M. J.
<strong>LRRK2 and Parkinson disease.</strong>
Arch. Neurol. 67: 542-547, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20457952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20457952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20457952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneurol.2010.79" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Di Fonzo2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Di Fonzo, A., Rohe, C. F., Ferreira, J., Chien, H. F., Vacca, L., Stocchi, F., Guedes, L., Fabrizio, E., Manfredi, M., Vanacore, N., Goldwurm, S., Breedveld, G., Sampaio, C., Meco, G., Barbosa, E., Oostra, B. A., Bonifati, V., Italian Parkinson Genetics Network.
<strong>A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease.</strong>
Lancet 365: 412-415, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15680456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15680456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15680456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/S0140-6736(05)17829-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Farrer2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Farrer, M., Stone, J., Mata, I. F., Lincoln, S., Kachergus, J., Hulihan, M., Strain, K. J., Maraganore, D. M.
<strong>LRRK2 mutations in Parkinson disease.</strong>
Neurology 65: 738-740, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16157908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16157908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16157908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000169023.51764.b0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Funayama2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Funayama, M., Hasegawa, K., Kowa, H., Saito, M., Tsuji, S., Obata, F.
<strong>A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1.</strong>
Ann. Neurol. 51: 296-301, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891824/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891824</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891824" 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/ana.10113" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Funayama2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Funayama, M., Hasegawa, K., Ohta, E., Kawashima, N., Komiyama, M., Kowa, H., Tsuji, S., Obata, F.
<strong>An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.</strong>
Ann. Neurol. 57: 918-921, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15880653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15880653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15880653" 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/ana.20484" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Gan-Or2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gan-Or, Z., Bar-Shira, A., Mirelman, A., Gurevich, T., Kedmi, M., Giladi, N., Orr-Urtreger, A.
<strong>LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease.</strong>
Neurogenetics 11: 121-125, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19458969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19458969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19458969" 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/s10048-009-0198-9" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Gehrke2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gehrke, S., Imai, Y., Sokol, N., Lu, B.
<strong>Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression.</strong>
Nature 466: 637-641, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20671708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20671708</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20671708[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=20671708" 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/nature09191" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Giasson2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Giasson, B. I., Covy, J. P., Bonini, N. M., Hurtig, H. I., Farrer, M. J., Trojanowski, J. Q., Van Deerlin, V. M.
<strong>Biochemical and pathological characterization of Lrrk2.</strong>
Ann. Neurol. 59: 315-322, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16437584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16437584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16437584" 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/ana.20791" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Gilks2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gilks, W. P., Abou-Sleiman, P. M., Gandhi, S., Jain, S., Singleton, A., Lees, A. J., Shaw, K., Bhatia, K. P., Bonifati, V., Quinn, N. P., Lynch, J., Healy, D. G., Holton, J. L., Revesz, T., Wood, N. W.
<strong>A common LRRK2 mutation in idiopathic Parkinson's disease.</strong>
Lancet 365: 415-416, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15680457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15680457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15680457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/S0140-6736(05)17830-1" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Girling1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Girling, R., Partridge, J. F., Bandara, L. R., Burden, N., Totty, N. F., Hsuan, J. J., La Thangue, N. B.
<strong>A new component of the transcription factor DRTF1/E2F.</strong>
Nature 362: 83-87, 1993. Note: Erratum: Nature 365: 468 only, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8446173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8446173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8446173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/362083a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Hasegawa1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hasegawa, K., Kowa, H.
<strong>Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy.</strong>
Europ. Neurol. 38 (suppl. 1): 39-43, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9276200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9276200</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9276200" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000113460" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Inzelberg2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Inzelberg, R., Cohen, O. S., Aharon-Peretz, J., Schlesinger, I., Gershoni-Baruch, R., Djaldetti, R., Nitsan, Z., Ephraty, L., Tunkel, O., Kozlova, E., Inzelberg, L., Kaplan, N., Fixler Mehr, T., Mory, A., Dagan, E., Schechtman, E., Friedman, E., Hassin-Baer, S.
<strong>The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers.</strong>
Neurology 78: 781-786, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22323743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e318249f673" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Ishihara2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ishihara, L., Warren, L., Gibson, R., Amouri, R., Lesage, S., Durr, A., Tazir, M., Wszolek, Z. K., Uitti, R. J., Nichols, W. C., Griffith, A., Hattori, N., Leppert, D., Watts, R., Zabetian, C. P., Foroud, T. M., Farrer, M. J., Brice, A., Middleton, L., Hentati, F.
<strong>Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations.</strong>
Arch. Neurol. 63: 1250-1254, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16966502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16966502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16966502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.63.9.1250" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Lee2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lee, B. D., Shin, J.-H., VanKampen, J., Petrucelli, L., West, A. B., Ko, H. S., Lee, Y.-I., Maguire-Zeiss, K. A., Bowers, W. J., Federoff, H. J., Dawson, V. L., Dawson, T. M.
<strong>Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease.</strong>
Nature Med. 16: 998-1000, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20729864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20729864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20729864[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=20729864" 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/nm.2199" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Lesage2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lesage, S., Belarbi, S., Troiano, A., Condroyer, C., Hecham, N., Pollak, P., Lohman, E., Benhassine, T., Ysmail-Dahlouk, F., Durr, A., Tazir, M., Brice, A.
<strong>Is the common LRRK2 G2019S mutation related to dyskinesias in North African Parkinson disease?</strong>
Neurology 71: 1550-1552, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18981379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18981379</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18981379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000338460.89796.06" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Lesage2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lesage, S., Condroyer, C., Lannuzel, A., Lohmann, E., Troiano, A., Tison, F., Damier, P., Thobois, S., Ouvrard-Hernandez, A.-M., Rivaud-Pechoux, S., Brefel-Courbon, C., Destee, A., Tranchant, C., Romana, M., Leclere, L., Durr, A., Brice, A.
<strong>Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease. (Letter)</strong>
J. Med. Genet. 46: 458-464, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19357115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19357115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19357115" 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.2008.062612" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Lesage2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lesage, S., Leutenegger, A.-L., Ibanez, P., Janin, S., Lohmann, E., Durr, A., Brice, A.
<strong>LRRK2 haplotype analysis in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century (Letter)</strong>
Am. J. Hum. Genet. 77: 330-332, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16145815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16145815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16145815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/432422" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Liu2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., Ren, Q., Jiao, Y., Sawa, A., Moran, T., Ross, C. A., Montell, C., Smith, W. W.
<strong>A Drosophila model for LRRK2-linked parkinsonism.</strong>
Proc. Nat. Acad. Sci. 105: 2693-2698, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18258746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18258746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18258746[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=18258746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.0708452105" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Marras2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Marras, C., Schule, B., Munhoz, R. P., Rogaeva, E., Langston, J. W., Kasten, M., Meaney, C., Klein, C., Wadia, P. M., Lim, S.-Y., Chuang, R. S.-I., Zadikof, C., and 10 others.
<strong>Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers.</strong>
Neurology 77: 325-333, 2011. Note: Erratum: Neurology 77: 1501 only, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21753163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21753163</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21753163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e318227042d" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Nandhagopal2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nandhagopal, R., Mak, E., Schulzer, M., McKenzie, J., McCormick, S., Sossi, V., Ruth, T. J., Strongosky, A., Farrer, M. J., Wszolek, Z. K., Stoessl, A. J.
<strong>Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study.</strong>
Neurology 71: 1790-1795, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19029519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19029519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19029519[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=19029519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000335973.66333.58" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Nichols2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nichols, W. C., Pankratz, N., Hernandez, D., Paisan-Ruiz, C., Jain, S., Halter, C. A., Michaels, V. E., Reed, T., Rudolph, A., Shults, C. W., Singleton, A., Foroud, T.
<strong>Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease.</strong>
Lancet 365: 410-412, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15680455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15680455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15680455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/S0140-6736(05)17828-3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Orr-Urtreger2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Orr-Urtreger, A., Shifrin, C., Rozovski, U., Rosner, S., Bercovich, D., Gurevich, T., Yagev-More, H., Bar-Shira, A., Giladi, N.
<strong>The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect?</strong>
Neurology 69: 1595-1602, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17938369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17938369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17938369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000277637.33328.d8" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Paisan-Ruiz2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Paisan-Ruiz, C., Jain, S., Evans, E. W., Gilks, W. P., Simon, J., van der Brug, M., Lopez de Munain, A., Aparicio, S., Martinez Gil, A., Khan, N., Johnson, J., Martinez, J. R., and 9 others.
<strong>Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease.</strong>
Neuron 44: 595-600, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15541308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15541308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15541308" 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.neuron.2004.10.023" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Paisan-Ruiz2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Paisan-Ruiz, C., Lang, A. E., Kawarai, T., Sato, C., Salehi-Rad, S., Fisman, G. K., Al-Khairallah, T., St George-Hyslop, P., Singleton, A., Rogaeva, E.
<strong>LRRK2 gene in Parkinson disease: mutation analysis and case control association study.</strong>
Neurology 65: 696-700, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16157901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16157901</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16157901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000167552.79769.b3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Paisan-Ruiz2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Paisan-Ruiz, C., Saenz, A., Lopez de Munain, A., Marti, I., Martinez Gil, A., Marti-Masso, J. F., Perez-Tur, J.
<strong>Familial Parkinson's disease: clinical and genetic analysis of four Basque families.</strong>
Ann. Neurol. 57: 365-372, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15732106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15732106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15732106" 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/ana.20391" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Rajput2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rajput, A., Dickson, D. W., Robinson, C. A., Ross, O. A., Dachsel, J. C., Lincoln, S. J., Cobb, S. A., Rajput, M. L., Farrer, M. J.
<strong>Parkinsonism, Lrrk2 G2019S, and tau neuropathology</strong>
Neurology 67: 1506-1508, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17060589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17060589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17060589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000240220.33950.0c" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Ross2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ross, O. A., Toft, M., Whittle, A. J., Johnson, J. L., Papapetropoulos, S., Mash, D. C., Litvan, I., Gordon, M. F., Wszolek, Z. K., Farrer, M. J., Dickson, D. W.
<strong>Lrrk2 and Lewy body disease.</strong>
Ann. Neurol. 59: 388-393, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16437559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16437559</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16437559" 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/ana.20731" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Satake2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Satake, W., Nakabayashi, Y., Mizuta, I., Hirota, Y., Ito, C., Kubo, M., Kawaguchi, T., Tsunoda, T., Watanabe, M., Takeda, A., Tomiyama, H., Nakashima, K., and 10 others.
<strong>Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. (Letter)</strong>
Nature Genet. 41: 1303-1307, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19915576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19915576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19915576" 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/ng.485" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Saunders-Pullman2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Saunders-Pullman, R., Stanley, K., Wang, C., San Luciano, M., Shanker, V., Hunt, A., Severt, L., Raymond, D., Ozelius, L. J., Lipton, R. B., Bressman, S. B.
<strong>Olfactory dysfunction in LRRK2 G2019S mutation carriers.</strong>
Neurology 77: 319-324, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21753159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21753159</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21753159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e318227041c" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Silveira-Moriyama2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Silveira-Moriyama, L., Guedes, L. C., Kingsbury, A., Ayling, H., Shaw, K., Barbosa, E. R., Bonifati, V., Quinn, N. P., Abou-Sleiman, P., Wood, N. W., Petrie, A., Sampaio, C., Ferreira, J. J., Holton, J., Revesz, T., Lees, A. J.
<strong>Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data.</strong>
Neurology 71: 1021-1026, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18809839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18809839</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18809839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000326575.20829.45" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Skipper2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Skipper, L., Li, Y., Bonnard, C., Pavanni, R., Yih, Y., Chua, E., Sung, W.-K., Tan, L., Wong, M.-C., Tan, E.-K., Liu, J.
<strong>Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease.</strong>
Hum. Molec. Genet. 14: 3549-3556, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16269443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16269443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16269443" 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/ddi376" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Tan2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tan, E.-K., Kwok, H.-H., Tan, L. C., Zhao, W.-T., Prakash, K. M., Au, W.-L., Pavanni, R., Ng, Y.-Y., Satake, W., Zhao, Y., Toda, T., Liu, J.-J.
<strong>Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus.</strong>
Neurology 75: 508-512, 2010. Note: Erratum: Neurology 75: 1399 only, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20697102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20697102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20697102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e3181eccfcd" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Wszolek1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wszolek, Z. K., Pfeiffer, B., Fulgham, J. R., Parisi, J. E., Thompson, B. M., Uitti, R. J., Calne, D. B., Pfeiffer, R. F.
<strong>Western Nebraska family (family D) with autosomal dominant parkinsonism.</strong>
Neurology 45: 502-505, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7898705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7898705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7898705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/wnl.45.3.502" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Wszolek2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wszolek, Z. K., Pfeiffer, R. F., Tsuboi, Y., Uitti, R. J., McComb, R. D., Stoessl, A. J., Strongosky, A. J., Zimprich, A., Muller-Myhsok, B., Farrer, M. J., Gasser, T., Calne, D. B., Dickson, D. W.
<strong>Autosomal dominant parkinsonism associated with variable synuclein and tau pathology.</strong>
Neurology 62: 1619-1622, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15136696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15136696</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15136696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000125015.06989.db" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Zhu2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zhu, X., Siedlak, S. L., Smith, M. A., Perry, G., Chen, S. G.
<strong>LRRK2 protein is a component of Lewy bodies. (Letter)</strong>
Ann. Neurol. 60: 617-618, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16847950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16847950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16847950" 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/ana.20928" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Zimprich2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R. J., Calne, D. B., Stoessl, A. J., Pfeiffer, R. F., Patenge, N., Carballo Carbajal, I., Vieregge, P., Asmus, F., Muller-Myhsok, B., Dickson, D. W., Meitinger, T., Strom, T. M., Wszolek, Z. K., Gasser, T.
<strong>Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.</strong>
Neuron 44: 601-607, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15541309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15541309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15541309" 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.neuron.2004.11.005" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="Zimprich2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zimprich, A., Muller-Myhsok, Farrer, M., Leitner, P., Sharma, M., Hulihan, M., Lockhart, P., Strongosky, A., Kachergus, J., Calne, D. B., Stoessel, J., Uitti, R. J., and 9 others.
<strong>The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval.</strong>
Am. J. Hum. Genet. 74: 11-19, 2004. Note: Erratum: Am. J. Med. Genet. 75: 534 only, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14691730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14691730</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14691730[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=14691730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/380647" 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 : 3/11/2013
</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">
Cassandra L. Kniffin - updated : 11/14/2011<br>Cassandra L. Kniffin - updated : 6/23/2011<br>Cassandra L. Kniffin - updated : 2/15/2011<br>Cassandra L. Kniffin - updated : 12/3/2010<br>Cassandra L. Kniffin - updated : 11/2/2010<br>Ada Hamosh - updated : 8/24/2010<br>Cassandra L. Kniffin - updated : 6/25/2010<br>Cassandra L. Kniffin - updated : 3/1/2010<br>Cassandra L. Kniffin - updated : 1/4/2010<br>Cassandra L. Kniffin - updated : 8/31/2009<br>George E. Tiller - updated : 4/23/2009<br>Cassandra L. Kniffin - updated : 3/16/2009<br>Cassandra L. Kniffin - updated : 1/9/2009<br>Cassandra L. Kniffin - updated : 10/28/2008<br>Cassandra L. Kniffin - updated : 5/28/2008<br>Cassandra L. Kniffin - updated : 4/2/2008<br>Cassandra L. Kniffin - updated : 3/13/2008<br>Cassandra L. Kniffin - updated : 9/12/2007<br>Cassandra L. Kniffin - updated : 11/6/2006<br>Cassandra L. Kniffin - updated : 4/20/2006<br>Cassandra L. Kniffin - updated : 11/7/2005<br>Cassandra L. Kniffin - updated : 8/26/2005<br>Cassandra L. Kniffin - updated : 5/11/2005<br>Cassandra L. Kniffin - updated : 2/9/2005<br>Cassandra L. Kniffin - updated : 11/2/2004<br>Victor A. McKusick - updated : 1/6/2004
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin : 6/24/2002
</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 : 11/03/2017
</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">
mcolton : 02/24/2014<br>alopez : 3/12/2013<br>alopez : 3/12/2013<br>ckniffin : 3/11/2013<br>terry : 5/24/2012<br>terry : 5/17/2012<br>carol : 11/16/2011<br>terry : 11/16/2011<br>ckniffin : 11/14/2011<br>wwang : 6/29/2011<br>ckniffin : 6/23/2011<br>wwang : 3/8/2011<br>ckniffin : 2/15/2011<br>carol : 1/28/2011<br>wwang : 12/6/2010<br>ckniffin : 12/3/2010<br>ckniffin : 11/17/2010<br>wwang : 11/2/2010<br>terry : 9/9/2010<br>mgross : 8/25/2010<br>terry : 8/24/2010<br>wwang : 6/29/2010<br>ckniffin : 6/25/2010<br>wwang : 3/4/2010<br>ckniffin : 3/1/2010<br>alopez : 1/4/2010<br>alopez : 1/4/2010<br>wwang : 9/11/2009<br>ckniffin : 8/31/2009<br>wwang : 5/13/2009<br>terry : 4/23/2009<br>wwang : 4/10/2009<br>ckniffin : 4/6/2009<br>wwang : 3/24/2009<br>ckniffin : 3/16/2009<br>wwang : 1/15/2009<br>ckniffin : 1/9/2009<br>wwang : 11/7/2008<br>ckniffin : 10/28/2008<br>wwang : 5/29/2008<br>ckniffin : 5/28/2008<br>wwang : 4/10/2008<br>ckniffin : 4/2/2008<br>wwang : 4/1/2008<br>ckniffin : 3/13/2008<br>wwang : 11/27/2007<br>wwang : 9/21/2007<br>ckniffin : 9/12/2007<br>wwang : 11/9/2006<br>ckniffin : 11/6/2006<br>carol : 6/21/2006<br>wwang : 4/25/2006<br>ckniffin : 4/20/2006<br>wwang : 11/15/2005<br>ckniffin : 11/7/2005<br>wwang : 9/6/2005<br>ckniffin : 8/26/2005<br>wwang : 5/18/2005<br>wwang : 5/13/2005<br>ckniffin : 5/11/2005<br>carol : 3/8/2005<br>tkritzer : 2/22/2005<br>ckniffin : 2/9/2005<br>ckniffin : 2/9/2005<br>carol : 11/2/2004<br>carol : 11/2/2004<br>ckniffin : 11/2/2004<br>carol : 8/26/2004<br>alopez : 3/17/2004<br>cwells : 1/7/2004<br>terry : 1/6/2004<br>carol : 6/26/2002<br>carol : 6/26/2002<br>ckniffin : 6/26/2002<br>ckniffin : 6/24/2002
</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> 607060
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
PARKINSON DISEASE 8, AUTOSOMAL DOMINANT; PARK8
</span>
</h3>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>ORPHA:</strong> 411602; &nbsp;
<strong>DO:</strong> 0060371; &nbsp;
</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">
12q12
</span>
</td>
<td>
<span class="mim-font">
{Parkinson disease 8}
</span>
</td>
<td>
<span class="mim-font">
607060
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
LRRK2
</span>
</td>
<td>
<span class="mim-font">
609007
</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 autosomal dominant Parkinson disease-8 (PARK8) is caused by heterozygous mutation in the LRRK2 gene (609007), which encodes dardarin, on chromosome 12q12.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).</p><p>Some patients with mutations in the LRRK2 gene may be classified as having Lewy body disease or Lewy body dementia (127750) or various forms of frontotemporal dementia (FTD; 600274).</p><p>Dachsel and Farrer (2010) provided a review of the LRRK2 gene and its role in Parkinson disease. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Hasegawa and Kowa (1997) reported a large Japanese family with autosomal dominant parkinsonism characterized by laterality of parkinsonism at onset, mean age of onset at 51 +/- 6 years, and favorable response to dopaminergic medication. Neuropathologic examination showed pure nigral degeneration without Lewy bodies or neurofibrillary tangles. </p><p>Wszolek et al. (1995) reported a large family from western Nebraska in which 18 members spanning 6 generations had slowly progressive parkinsonism inherited in an autosomal dominant pattern. The family's ancestors probably immigrated to the United States from England. Clinical features included bradykinesia, rigidity, resting tremor, postural instability, and favorable response to levodopa. Postmortem examination of 1 affected individual showed neuronal and pigmentary loss, gliosis, and Lewy bodies in the substantia nigra. In a follow-up report of the same family, Wszolek et al. (2004) reported 4 additional affected members. Mean age at onset for all patients was 65 years. Pathologic examination of 4 patients showed neuronal loss and gliosis in the substantia nigra in all, but variable findings, including Lewy bodies in only 2 of 4 patients and tau (MAPT; 157140) pathology in 1 of 4, were also seen. Using PET scan to evaluate presynaptic dopaminergic integrity of the putamen in members of the family originally reported by Wszolek et al. (1995), Nandhagopal et al. (2008) found that 2 asymptomatic LRRK2 mutation carriers had progressive dopaminergic dysfunction affecting transport and uptake compared to 2 family members without the mutation over a 2- to 3-year span. One of the asymptomatic mutation carriers developed subtle clinical manifestations of PD by the time of the second scan. The findings suggested that PET abnormalities are present in asymptomatic carriers early in the illness. </p><p>Paisan-Ruiz et al. (2004) reported 4 families from the Basque region of Spain and 1 family from the United Kingdom with autosomal dominant Parkinson disease. Mean age at onset was 65 years, followed by a benign course with excellent response to low doses of L-DOPA. The majority of patients presented with unilateral leg or hand tremor. No cognitive decline was noted in any of the patients even after long disease duration. Paisan-Ruiz et al. (2005) reported that PET scan of 1 of the Basque patients showed nigrostriatal dysfunction with a typical pattern of idiopathic presynaptic Parkinson disease. </p><p><strong><em>Pathologic Findings</em></strong></p><p>
The neuropathologic findings in patients with LRRK2 mutations are pleomorphic. The most common findings include classic alpha-synuclein (SNCA; 163890)- positive Lewy bodies and Lewy neurites, but these are not always present. Other less common findings include tau (MAPT; 157140)- and ubiquitin (UBB; 191339)-immunoreactive inclusions (Zimprich et al., 2004; Giasson et al., 2006; Ross et al., 2006). </p><p>Giasson et al. (2006) reported detailed neuropathologic findings of 3 patients with PARK8 who carried the common LRRK2 G2019S mutation (609007.0006). All showed extensive loss of pigmented neurons in the substantia nigra and locus ceruleus. Classic Lewy bodies were identified in 2 patients, 1 of whom also showed senile plaques and neurofibrillary tangles consistent with Alzheimer disease (104300), which may be have been part of normal aging. The third patient, who did not show Lewy bodies, uniquely demonstrated dystrophic neurons in the substantia nigra that stained intensely for LRRK2. Similar LRRK2 inclusions were not observed in analysis of more than 40 other brains with diverse neurodegenerative diseases. </p><p>Ross et al. (2006) reported neuropathologic findings of 8 patients with PD or Lewy body disease who carried the LRRK2 G2019S mutation. All had classic Lewy bodies with a range of distribution from the brainstem to diffuse regions of the brain, but there was no apparent correlation between Lewy body pathology and disease progression. Three patients had a family history of PD. Four patients had autonomic dysfunction, 2 had dementia with Lewy bodies, and 1 had dementia with Alzheimer disease. One healthy control individual with the G2019S mutation who died at age 68 years had no significant neuropathologic findings, consistent with reduced penetrance; another control with the G2019S mutation had concomitant Alzheimer disease. </p><p>By postmortem examination of a man with PD who carried the G2019S mutation, Rajput et al. (2006) found a medial temporal tauopathy and Alzheimer-type pathology with cortical amyloid deposits and neurofibrillary deposits in multiple deep brain regions. Lewy bodies were not observed, and there was not significant neuronal loss outside of the substantia nigra. Coimmunoprecipitation studies showed no evidence of a direct interaction between LRRK2 and MAPT. </p><p>Using antibodies to LRRK2 epitopes located outside the folded domains of the protein, Zhu et al. (2006) found LRRK2 immunoreactivity within Lewy bodies of patients with sporadic PD. The findings suggested that LRRK2 is a component of Lewy bodies. However, Covy et al. (2006) concluded that LRRK2 is not present in Lewy bodies, based on their studies of various LRRK2 antibodies. Covy et al. (2006) suggested that cross-reactivity with other proteins may occur. </p><p><strong><em>Clinical Variability</em></strong></p><p>
In a series of 434 cases of various neurodegenerative disorders, Chen-Plotkin et al. (2008) identified 2 unrelated patients with a clinical diagnosis of corticobasal degeneration and primary progressive aphasia, respectively, who were found to have heterozygous mutations in the LRRK2 gene. These diagnoses fall within the broad clinical category of frontotemporal dementia (FTD; 600274). The first patient, who carried the common G2019S mutation, developed difficulties in planning, organization, and memory at age 52 years. The disorder was progressive, and she later developed apraxia and extrapyramidal features including increased tone and shuffling gait. She never developed tremor. The second patient, who had a preexisting seizure disorder, presented at age 66 years with progressive speech difficulties that developed into expressive aphasia, and cognitive impairment. She had intention tremor and mild flattening of the right nasolabial fold. Brain MRI showed cortical atrophy of the left temporal lobe. Chen-Plotkin et al. (2008) concluded that the LRRK2-associated neurodegenerative phenotype may be more heterogeneous than previously assumed. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Gehrke et al. (2010) found that LRRK2 interacted with the microRNA (miRNA) pathway to regulate protein synthesis. They showed that mRNAs for Drosophila E2f1 (189971) and Dp (TFDP1; 189902), which had previously been implicated in cell cycle and survival control (Girling et al., 1993), were translationally repressed by the miRNAs Let7 (MIRLET7A1; 605386) and miR184* (613146), respectively. Pathogenic human LRRK2 antagonized Let7 and miR184*, leading to overproduction of E2f1 and Dp, which was critical for LRRK2 pathogenesis. In Drosophila, genetic deletion of Let7, antagomir-mediated blockage of Let7 and miR184* action, transgenic expression of Dp target protector, or replacement of endogenous Dp with a Dp transgene nonresponsive to Let7 each had toxic effects similar to those of pathogenic LRRK2. Conversely, increasing the level of Let7 or miR184* attenuated pathogenic LRRK2 effects. Human LRRK2 associated with Drosophila Argonaute-1 (EIF2C1, or AGO1; 606228) or human Argonaute-2 (EIF2C2, or AGO2; 606229) of the RNA-induced silencing complex (RISC). In aged fly brain, Ago1 protein level was negatively regulated by human LRRK2. Furthermore, pathogenic LRRK2 promoted the association of phosphorylated 4EBP1 (EIF4EPB1; 602223) with human AGO2. Gehrke et al. (2010) concluded that deregulated synthesis of E2F1 and DP caused by miRNA pathway impairment is a key event in LRRK2 pathogenesis, suggesting that novel miRNA-based therapeutic strategies may be useful for Parkinson disease. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Other Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Silveira-Moriyama et al. (2008) found that 19 patients with PARK8 and the common G2019S mutation (609007.0006) scored lower on a test of smell, indicating decreased olfactory function and hyposmia, compared to controls or to 2 asymptomatic G2019S carriers. Postmortem examination of the rhinencephalon in 4 PARK8 patients, only 1 of whom had been clinically tested and had hyposmia, showed alpha-synuclein accumulation in olfactory pathways. The authors commented that hyposmia has been reported in up to 80% of patients with Parkinson disease. </p><p>Saunders-Pullman et al. (2011) examined olfaction in 31 individuals with G2019S-related PD, 30 with non-LRRK2 PD, 28 nonmanifesting G2019S carriers, and 46 controls. The mean score of all those with PD reflected impaired olfaction compared to controls, although G2019S-related PD patients had less severe impairment compared to non-LRRK2 PD patients. Nonmanifesting LRRK2 mutation carriers had subtle olfactory impairment that was less severe than that in manifesting mutation carriers. However, the study could not determine if the subtle olfactory deficit in nonmanifesting disease carriers could predict future development of motor symptoms, and the authors suggested that longitudinal studies were warranted. </p><p>Marras et al. (2011) examined the clinical features of 112 individuals from 15 families with the G2019S mutation, including 25 PD-manifesting mutation carriers and 29 nonmanifesting mutation carriers (54 mutation carriers total). Among the manifesting carriers, tremor was the most commonly recognized initial symptom, and tremor, postural instability, and gait disorders were most common even in early disease. Olfaction was abnormal only in 2 of 7 with short disease duration, but was abnormal in 8 of 10 with long disease duration. Eleven of 19 manifesting patients tested showed impaired color discrimination. Compared to 84 individuals with idiopathic PD, G2019S PD patients had better olfactory sense, worse depression scores, worse color discrimination, more common tremor at presentation and gait dysfunction, and slightly better motor scores earlier in disease duration. However, the phenotypes were largely overlapping. Nonmanifesting mutation carriers had an increased frequency of tremor (31%) compared to noncarriers (12%) and to unrelated controls (13%). Nonmanifesting mutation carriers had increased constipation (12%) compared to controls (2%), as well as worse color discrimination compared to controls. </p><p>Aasly et al. (2012) studied 26 patients with LRRK2 mutations, including 18 asymptomatic carriers and 8 patients at an early stage of PD. Symptomatic patients had reduced CSF levels of beta-amyloid-42 (APP; 104760), total tau (MAPT; 157140), and phosphorylated tau compared to asymptomatic mutation carriers. PET scan for 3 markers of dopaminergic function in the striatum showed significantly reduced values for all 3 markers in all symptomatic mutation carriers, whereas only 4 asymptomatic mutations carriers had reduction of all 3 tracers studied. There was a trend towards a correlation between decreased striatal dopaminergic function and reduced CSF beta-amyloid-42 and tau levels, with significant values only for beta-amyloid-42 and fluorodopa uptake. When cases were restricted to those with the G2019S mutation, significant correlations were also observed for tau. The findings suggested a link between beta-amyloid and tau deposition and the pathogenesis of LRRK2-related PD. However, Aasly et al. (2012) noted that this was an exploratory study, that the data should be interpreted with caution, and that the results need to be replicated. </p><p>In a cross-sectional study of 490 Jewish patients with PD, Inzelberg et al. (2012) found that 79 (16.1%) carried the common G2019S mutation. Eighteen (23%) G2019S mutation carriers had a non-skin cancer compared to 49 (12%) nonmutation carriers (odds ratio = 2.18). A significant ethnicity effect was noted for those of Ashkenazi Jewish ancestry: the age-adjusted odds ratio for the development of non-skin cancer among Ashkenazi Jewish carriers of the G2019S mutation was 3.38. The most common cancer was breast, which accounted for 15% of the cancer types. The LRRK2 G2019S causes a gain of function for the kinase, which could potentially play a role in tumorigenesis. However, Bandmann and Cookson (2012) noted that the study showed an association between G2019S and non-skin cancer, but did not prove causation. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Funayama et al. (2002) performed a genomewide linkage analysis in the family reported by Hasegawa and Kowa (1997). Allele typing was performed for 31 individuals from 4 generations. Parametric 2-point linkage analysis yielded a maximum lod score of 4.32 at D12S345 (12p11.2). Parametric multipoint linkage analysis of the 13.6-cM interval around this marker yielded lod scores greater than 4.0 at D12S85 (12q12). Haplotype analysis showed 2 recombination events which further defined the candidate region. The haplotype was shared by 15 affected individuals and by 8 unaffected individuals, which raised the possibility of incomplete penetrance. Nonparametric linkage analysis also supported mapping of the parkinsonism locus to 12p11.2-q13.1. </p><p>In 21 Caucasian families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission, Zimprich et al. (2004) tested for linkage to the PARK8 region. Two families, one a German Canadian family and the other a family from western Nebraska (Wszolek et al., 1995), reached significant linkage on their own, with a combined maximum multipoint lod score of 3.33. </p><p>In a genomewide association study and 2 replication studies in a total of 2,011 cases and 18,381 controls from Japan, Satake et al. (2009) found strong association with the LRRK2 gene (609007) on 12q12 (p = 2.72 x 10(-8)), implicated in PARK8. Tan et al. (2010) specifically analyzed 3 SNPs at the PARK8 locus in 433 PD patients and 916 controls, all of Chinese ethnicity, and independently confirmed a significant association with PARK8. </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 Basque families and 1 English family with autosomal dominant PD, Paisan-Ruiz et al. (2004) identified 2 different heterozygous mutations in the LRRK2 gene (609007.0001 and 609007.0002, respectively). The disease showed 100% penetrance. </p><p>In affected members of a Nebraskan kindred with autosomal dominant PD originally reported by Wszolek et al. (1995), Zimprich et al. (2004) identified a heterozygous mutation in the LRRK2 gene (609007.0003). </p><p>In affected members of 4 of 61 (6.6%) families with autosomal dominant PD, Di Fonzo et al. (2005) identified a heterozygous gly2019-to-ser (G2019S; 609007.0006) mutation in the LRRK2 gene. Two families were from Italy, and 1 each were from Portugal and Brazil. Gilks et al. (2005) identified the G2019S mutation in 8 of 482 (1.6%) unrelated patients with Parkinson disease. Five of the patients had no family history of the disorder, suggesting either a de novo occurrence or reduced penetrance. Nichols et al. (2005) identified the G2019S mutation in 20 of 358 (6%) families with PD. In 1 family, 1 sib was heterozygous for the mutation and another was homozygous; the homozygous individual did not differ in clinical presentation from the sib and did not have early disease onset or more rapid progression. Nichols et al. (2005) suggested genetic screening for the G2019S mutation in patients with familial PD. </p><p>In all 19 affected members of the original Japanese family with PARK8 (Hasegawa and Kowa, 1997), Funayama et al. (2005) identified a heterozygous mutation in the LRRK2 gene (609007.0007). </p><p>Farrer et al. (2005) identified pathogenic mutations in the LRRK2 gene in 5 (0.6%) of 786 probands with idiopathic Parkinson disease. Four probands carried the common G2019S mutation. </p><p>Paisan-Ruiz et al. (2005) identified 2 different LRRK2 mutations in 3 of 23 unrelated probands with autosomal dominant Parkinson disease. Two probands had the common G2019S mutation. In a case-control study of 121 unrelated Parkinson disease patients and 250 controls, Paisan-Ruiz et al. (2005) found no association between PD and any of 4 LRRK2 polymorphisms examined. </p><p>Ishihara et al. (2006) found no observable phenotypic differences between 26 patients with Parkinson disease who were homozygous for the G2019S mutation, including 20 patients of Tunisian origin, and reports of patients who were heterozygous for the mutation. In addition, 3 clinically unaffected Tunisian individuals were homozygous for the mutation at ages 42, 45, and 70 years. The findings did not support a gene dosage effect. </p><p>Alcalay et al. (2010) identified the G2019S mutation in 35 (3.6%) of 953 patients with early-onset PD before age 51, including 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Four of the 35 patients had the G2019S mutation and another mutation in the PRKN (PARK2; 602544) or GBA genes (606463). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Alcalay et al. (2009) found that 34 (3.7%) of 925 patients with early-onset PD, defined as age at onset before age 51 years, carried the G2019S mutation. Compared to noncarriers, carriers of the G2019S mutation were more likely to be of Ashkenazi Jewish descent (55.9% vs 11.9%), to have a lower tremor score (p = 0.03), and to have a higher score of postural instability and gait difficulty (PIGD; 92.3% vs 58.9%, p = 0.003). The PIGD phenotype in general is associated with a more severe phenotype and a faster rate of cognitive decline compared to the tremor dominant phenotype, so the findings of this study suggested implications for disease course in G2019S mutation carriers. </p><p>Mutations in the LRRK2 gene and the GBA gene commonly predispose to PD in individuals of Ashkenazi Jewish descent. Gan-Or et al. (2010) screened a cohort of 600 Ashkenazi PD patients for the common LRRK2 G2019S mutation and for 8 GBA mutations. Among all patients, 117 (19.5%) were heterozygous for GBA mutations, and 82 (13.7%) were heterozygous for the LRRK2 G2019S mutation, including 8 patients carrying both GBA and LRRK2 mutations. There were 6 (1.0%) homozygotes or compound heterozygotes GBA mutations carriers, and 1 (0.2%) patient homozygote for G2019S. Carriers of LRRK2 G2019S or GBA mutations had a significantly earlier average age at onset (57.5 and 57.5 years) than noncarriers (61.0 years); the 8 with mutations in both genes had a similar average age at onset (57.4 years). A phenotypic comparison of those with the G2019S mutation, GBA mutations, and noncarriers of these mutations showed that more of those with the G2019S mutation reported muscle stiffness/rigidity (p = 0.007) and balance disturbances (p = 0.008), while more GBA mutation carriers reported slowness/bradykinesia (p = 0.021). However, the most common presenting symptom in both groups was tremor (about 50%). These results suggested distinct effects of LRRK2 or GBA mutations on the initial symptoms of PD in some cases. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Orr-Urtreger et al. (2007) identified a heterozygous G2019S mutation in 12.3% of 472 Jewish PD patients, and in 14.8% of the 344 patients in this group who were specifically of Ashkenazi Jewish origin. The mutation was also detected in 2.4% of Ashkenazi Jewish controls. A common shared haplotype identified by Lesage et al. (2005) was found in 97% of mutation carriers. None of 42 Jewish patients from Iraq or Morocco carried the G2019S mutation. </p><p>Skipper et al. (2005) identified a subset of tagging-SNPs (tSNP) that captured the majority of common variation within the LRRK2. Both single tSNP and tSNP haplotype analyses, using a large epidemiologically-matched sporadic case-control series comprising 932 Chinese individuals, yielded significant evidence for association with Parkinson disease. The authors identified a haplotype that dramatically increased disease risk when present in 2 copies (odds ratio = 5.5; P = 0.0001). </p><p>Choi et al. (2008) did not identify the G2019S mutation in 72 unrelated Korean patients with onset of PD before age 50, suggesting that it is not a common cause of PD in this population. </p><p>Lesage et al. (2008) identified the G2019S mutation in 7 (41%) of 17 North African patients with familial PD and 40 (34%) of 119 North African patients with sporadic PD. All were heterozygous for the mutation except 3 patients, who were homozygous. One (1.5%) of 66 Algerian controls was homozygous for the mutation, but showed no evidence of disease at age 41 years, which is younger than the average age of disease onset. </p><p>Lesage et al. (2009) found 8 potentially or proven pathogenic mutations, including 4 novel mutations, in the LRRK2 gene in 22 (9.7%) of 226 probands with autosomal dominant Parkinson disease, including 182 from France and 14 from North Africa. The common G2019S mutation was identified in 13 (5.8%) probands, including 6 (43%) from North Africa. Heterozygous mutations R1441H (609007.0008) and I1371V were found in 2 probands each. Most of the mutations were located in the functional domains of the LRRK2 protein. Some of the patients had been previously reported. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Liu et al. (2008) found that Drosophila expressing the human LRRK2 G2019S mutation in neuronal cells showed adult-onset loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Overexpression of LRRK2 resulted in a less severe form of parkinsonism. Treatment of mutant flies with L-DOPA improved locomotor impairment but did not prevent loss of dopaminergic cells. Expression of mutant protein in photoreceptor cells resulted in retinal degeneration. The findings provided a gain-of-function animal model for human LRRK2-linked PD. </p><p>Lee et al. (2010) presented evidence demonstrating that pharmacologic inhibitors of LRRK2 kinase activity are protective in both in vitro and in vivo mouse models of LRRK2-induced neurodegeneration. </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">
Aasly, J. O., Shi, M., Sossi, V., Stewart, T., Johansen, K. K., Wszolek, Z. K., Uitti, R. J., Hasegawa, K., Yokoyama, T., Zabetian, C. P., Kim, H. M., Leverenz, J. B., Ginghina, C., Armaly, J., Edwards, K. L., Snapinn, K. W., Stoessl, A. J., Zhang, J.
<strong>Cerebrospinal fluid amyloid beta and tau in LRRK2 mutation carriers.</strong>
Neurology 78: 55-61, 2012.
[PubMed: 22170881]
[Full Text: https://doi.org/10.1212/WNL.0b013e31823ed101]
</p>
</li>
<li>
<p class="mim-text-font">
Alcalay, R. N., Caccappolo, E., Mejia-Santana, H., Tang, M. X., Rosado, L., Ross, B. M., Verbitsky, M., Kisselev, S., Louis, E. D., Comella, C., Colcher, A., Jennings, D., and 21 others.
<strong>Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the Consortium on Risk for Early Onset Parkinson Disease study.</strong>
Arch. Neurol. 67: 1116-1122, 2010.
[PubMed: 20837857]
[Full Text: https://doi.org/10.1001/archneurol.2010.194]
</p>
</li>
<li>
<p class="mim-text-font">
Alcalay, R. N., Mejia-Santana, H., Tang, M. X., Rosado, L., Verbitsky, M., Kisselev, S., Ross, B. M., Louis, E. D., Comella, C. L., Colcher, A., Jennings, D., Nance, M. A., and 21 others.
<strong>Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease.</strong>
Arch. Neurol. 66: 1517-1522, 2009.
[PubMed: 20008657]
[Full Text: https://doi.org/10.1001/archneurol.2009.267]
</p>
</li>
<li>
<p class="mim-text-font">
Bandmann, O., Cookson, M. R.
<strong>Parkinson disease, cancer, and LRRK2: causation or association?</strong>
Neurology 78: 772-773, 2012.
[PubMed: 22323745]
[Full Text: https://doi.org/10.1212/WNL.0b013e318249f744]
</p>
</li>
<li>
<p class="mim-text-font">
Chen-Plotkin, A. S., Yuan, W., Anderson, C., Wood, E. M., Hurtig, H. I., Clark, C. M., Miller, B. L., Lee, V. M.-Y., Trojanowski, J. Q., Grossman, M., Van Deerlin, V. M.
<strong>Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations.</strong>
Neurology 70: 521-527, 2008.
[PubMed: 17914064]
[Full Text: https://doi.org/10.1212/01.WNL.0000280574.17166.26]
</p>
</li>
<li>
<p class="mim-text-font">
Choi, J. M., Woo, M. S., Ma, H.-I., Kang, S. Y., Sung, Y.-H., Yong, S. W., Chung, S. J., Kim, J.-S., Shin, H., Lyoo, C. H., Lee, P. H., Baik, J. S., and 9 others.
<strong>Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.</strong>
Neurogenetics 9: 263-269, 2008.
[PubMed: 18704525]
[Full Text: https://doi.org/10.1007/s10048-008-0138-0]
</p>
</li>
<li>
<p class="mim-text-font">
Covy, J. P., Van Deerlin, V. M., Giasson, B. I.
<strong>Lack of evidence for Lrrk2 in alpha-synuclein pathological inclusions. (Letter)</strong>
Ann. Neurol. 60: 618-619, 2006.
</p>
</li>
<li>
<p class="mim-text-font">
Dachsel, J. C., Farrer, M. J.
<strong>LRRK2 and Parkinson disease.</strong>
Arch. Neurol. 67: 542-547, 2010.
[PubMed: 20457952]
[Full Text: https://doi.org/10.1001/archneurol.2010.79]
</p>
</li>
<li>
<p class="mim-text-font">
Di Fonzo, A., Rohe, C. F., Ferreira, J., Chien, H. F., Vacca, L., Stocchi, F., Guedes, L., Fabrizio, E., Manfredi, M., Vanacore, N., Goldwurm, S., Breedveld, G., Sampaio, C., Meco, G., Barbosa, E., Oostra, B. A., Bonifati, V., Italian Parkinson Genetics Network.
<strong>A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson&#x27;s disease.</strong>
Lancet 365: 412-415, 2005.
[PubMed: 15680456]
[Full Text: https://doi.org/10.1016/S0140-6736(05)17829-5]
</p>
</li>
<li>
<p class="mim-text-font">
Farrer, M., Stone, J., Mata, I. F., Lincoln, S., Kachergus, J., Hulihan, M., Strain, K. J., Maraganore, D. M.
<strong>LRRK2 mutations in Parkinson disease.</strong>
Neurology 65: 738-740, 2005.
[PubMed: 16157908]
[Full Text: https://doi.org/10.1212/01.wnl.0000169023.51764.b0]
</p>
</li>
<li>
<p class="mim-text-font">
Funayama, M., Hasegawa, K., Kowa, H., Saito, M., Tsuji, S., Obata, F.
<strong>A new locus for Parkinson&#x27;s disease (PARK8) maps to chromosome 12p11.2-q13.1.</strong>
Ann. Neurol. 51: 296-301, 2002.
[PubMed: 11891824]
[Full Text: https://doi.org/10.1002/ana.10113]
</p>
</li>
<li>
<p class="mim-text-font">
Funayama, M., Hasegawa, K., Ohta, E., Kawashima, N., Komiyama, M., Kowa, H., Tsuji, S., Obata, F.
<strong>An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.</strong>
Ann. Neurol. 57: 918-921, 2005.
[PubMed: 15880653]
[Full Text: https://doi.org/10.1002/ana.20484]
</p>
</li>
<li>
<p class="mim-text-font">
Gan-Or, Z., Bar-Shira, A., Mirelman, A., Gurevich, T., Kedmi, M., Giladi, N., Orr-Urtreger, A.
<strong>LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease.</strong>
Neurogenetics 11: 121-125, 2010.
[PubMed: 19458969]
[Full Text: https://doi.org/10.1007/s10048-009-0198-9]
</p>
</li>
<li>
<p class="mim-text-font">
Gehrke, S., Imai, Y., Sokol, N., Lu, B.
<strong>Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression.</strong>
Nature 466: 637-641, 2010.
[PubMed: 20671708]
[Full Text: https://doi.org/10.1038/nature09191]
</p>
</li>
<li>
<p class="mim-text-font">
Giasson, B. I., Covy, J. P., Bonini, N. M., Hurtig, H. I., Farrer, M. J., Trojanowski, J. Q., Van Deerlin, V. M.
<strong>Biochemical and pathological characterization of Lrrk2.</strong>
Ann. Neurol. 59: 315-322, 2006.
[PubMed: 16437584]
[Full Text: https://doi.org/10.1002/ana.20791]
</p>
</li>
<li>
<p class="mim-text-font">
Gilks, W. P., Abou-Sleiman, P. M., Gandhi, S., Jain, S., Singleton, A., Lees, A. J., Shaw, K., Bhatia, K. P., Bonifati, V., Quinn, N. P., Lynch, J., Healy, D. G., Holton, J. L., Revesz, T., Wood, N. W.
<strong>A common LRRK2 mutation in idiopathic Parkinson&#x27;s disease.</strong>
Lancet 365: 415-416, 2005.
[PubMed: 15680457]
[Full Text: https://doi.org/10.1016/S0140-6736(05)17830-1]
</p>
</li>
<li>
<p class="mim-text-font">
Girling, R., Partridge, J. F., Bandara, L. R., Burden, N., Totty, N. F., Hsuan, J. J., La Thangue, N. B.
<strong>A new component of the transcription factor DRTF1/E2F.</strong>
Nature 362: 83-87, 1993. Note: Erratum: Nature 365: 468 only, 1993.
[PubMed: 8446173]
[Full Text: https://doi.org/10.1038/362083a0]
</p>
</li>
<li>
<p class="mim-text-font">
Hasegawa, K., Kowa, H.
<strong>Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy.</strong>
Europ. Neurol. 38 (suppl. 1): 39-43, 1997.
[PubMed: 9276200]
[Full Text: https://doi.org/10.1159/000113460]
</p>
</li>
<li>
<p class="mim-text-font">
Inzelberg, R., Cohen, O. S., Aharon-Peretz, J., Schlesinger, I., Gershoni-Baruch, R., Djaldetti, R., Nitsan, Z., Ephraty, L., Tunkel, O., Kozlova, E., Inzelberg, L., Kaplan, N., Fixler Mehr, T., Mory, A., Dagan, E., Schechtman, E., Friedman, E., Hassin-Baer, S.
<strong>The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers.</strong>
Neurology 78: 781-786, 2012.
[PubMed: 22323743]
[Full Text: https://doi.org/10.1212/WNL.0b013e318249f673]
</p>
</li>
<li>
<p class="mim-text-font">
Ishihara, L., Warren, L., Gibson, R., Amouri, R., Lesage, S., Durr, A., Tazir, M., Wszolek, Z. K., Uitti, R. J., Nichols, W. C., Griffith, A., Hattori, N., Leppert, D., Watts, R., Zabetian, C. P., Foroud, T. M., Farrer, M. J., Brice, A., Middleton, L., Hentati, F.
<strong>Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations.</strong>
Arch. Neurol. 63: 1250-1254, 2006.
[PubMed: 16966502]
[Full Text: https://doi.org/10.1001/archneur.63.9.1250]
</p>
</li>
<li>
<p class="mim-text-font">
Lee, B. D., Shin, J.-H., VanKampen, J., Petrucelli, L., West, A. B., Ko, H. S., Lee, Y.-I., Maguire-Zeiss, K. A., Bowers, W. J., Federoff, H. J., Dawson, V. L., Dawson, T. M.
<strong>Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson&#x27;s disease.</strong>
Nature Med. 16: 998-1000, 2010.
[PubMed: 20729864]
[Full Text: https://doi.org/10.1038/nm.2199]
</p>
</li>
<li>
<p class="mim-text-font">
Lesage, S., Belarbi, S., Troiano, A., Condroyer, C., Hecham, N., Pollak, P., Lohman, E., Benhassine, T., Ysmail-Dahlouk, F., Durr, A., Tazir, M., Brice, A.
<strong>Is the common LRRK2 G2019S mutation related to dyskinesias in North African Parkinson disease?</strong>
Neurology 71: 1550-1552, 2008.
[PubMed: 18981379]
[Full Text: https://doi.org/10.1212/01.wnl.0000338460.89796.06]
</p>
</li>
<li>
<p class="mim-text-font">
Lesage, S., Condroyer, C., Lannuzel, A., Lohmann, E., Troiano, A., Tison, F., Damier, P., Thobois, S., Ouvrard-Hernandez, A.-M., Rivaud-Pechoux, S., Brefel-Courbon, C., Destee, A., Tranchant, C., Romana, M., Leclere, L., Durr, A., Brice, A.
<strong>Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson&#x27;s disease. (Letter)</strong>
J. Med. Genet. 46: 458-464, 2009.
[PubMed: 19357115]
[Full Text: https://doi.org/10.1136/jmg.2008.062612]
</p>
</li>
<li>
<p class="mim-text-font">
Lesage, S., Leutenegger, A.-L., Ibanez, P., Janin, S., Lohmann, E., Durr, A., Brice, A.
<strong>LRRK2 haplotype analysis in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century (Letter)</strong>
Am. J. Hum. Genet. 77: 330-332, 2005.
[PubMed: 16145815]
[Full Text: https://doi.org/10.1086/432422]
</p>
</li>
<li>
<p class="mim-text-font">
Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., Ren, Q., Jiao, Y., Sawa, A., Moran, T., Ross, C. A., Montell, C., Smith, W. W.
<strong>A Drosophila model for LRRK2-linked parkinsonism.</strong>
Proc. Nat. Acad. Sci. 105: 2693-2698, 2008.
[PubMed: 18258746]
[Full Text: https://doi.org/10.1073/pnas.0708452105]
</p>
</li>
<li>
<p class="mim-text-font">
Marras, C., Schule, B., Munhoz, R. P., Rogaeva, E., Langston, J. W., Kasten, M., Meaney, C., Klein, C., Wadia, P. M., Lim, S.-Y., Chuang, R. S.-I., Zadikof, C., and 10 others.
<strong>Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers.</strong>
Neurology 77: 325-333, 2011. Note: Erratum: Neurology 77: 1501 only, 2011.
[PubMed: 21753163]
[Full Text: https://doi.org/10.1212/WNL.0b013e318227042d]
</p>
</li>
<li>
<p class="mim-text-font">
Nandhagopal, R., Mak, E., Schulzer, M., McKenzie, J., McCormick, S., Sossi, V., Ruth, T. J., Strongosky, A., Farrer, M. J., Wszolek, Z. K., Stoessl, A. J.
<strong>Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study.</strong>
Neurology 71: 1790-1795, 2008.
[PubMed: 19029519]
[Full Text: https://doi.org/10.1212/01.wnl.0000335973.66333.58]
</p>
</li>
<li>
<p class="mim-text-font">
Nichols, W. C., Pankratz, N., Hernandez, D., Paisan-Ruiz, C., Jain, S., Halter, C. A., Michaels, V. E., Reed, T., Rudolph, A., Shults, C. W., Singleton, A., Foroud, T.
<strong>Genetic screening for a single common LRRK2 mutation in familial Parkinson&#x27;s disease.</strong>
Lancet 365: 410-412, 2005.
[PubMed: 15680455]
[Full Text: https://doi.org/10.1016/S0140-6736(05)17828-3]
</p>
</li>
<li>
<p class="mim-text-font">
Orr-Urtreger, A., Shifrin, C., Rozovski, U., Rosner, S., Bercovich, D., Gurevich, T., Yagev-More, H., Bar-Shira, A., Giladi, N.
<strong>The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect?</strong>
Neurology 69: 1595-1602, 2007.
[PubMed: 17938369]
[Full Text: https://doi.org/10.1212/01.wnl.0000277637.33328.d8]
</p>
</li>
<li>
<p class="mim-text-font">
Paisan-Ruiz, C., Jain, S., Evans, E. W., Gilks, W. P., Simon, J., van der Brug, M., Lopez de Munain, A., Aparicio, S., Martinez Gil, A., Khan, N., Johnson, J., Martinez, J. R., and 9 others.
<strong>Cloning of the gene containing mutations that cause PARK8-linked Parkinson&#x27;s disease.</strong>
Neuron 44: 595-600, 2004.
[PubMed: 15541308]
[Full Text: https://doi.org/10.1016/j.neuron.2004.10.023]
</p>
</li>
<li>
<p class="mim-text-font">
Paisan-Ruiz, C., Lang, A. E., Kawarai, T., Sato, C., Salehi-Rad, S., Fisman, G. K., Al-Khairallah, T., St George-Hyslop, P., Singleton, A., Rogaeva, E.
<strong>LRRK2 gene in Parkinson disease: mutation analysis and case control association study.</strong>
Neurology 65: 696-700, 2005.
[PubMed: 16157901]
[Full Text: https://doi.org/10.1212/01.wnl.0000167552.79769.b3]
</p>
</li>
<li>
<p class="mim-text-font">
Paisan-Ruiz, C., Saenz, A., Lopez de Munain, A., Marti, I., Martinez Gil, A., Marti-Masso, J. F., Perez-Tur, J.
<strong>Familial Parkinson&#x27;s disease: clinical and genetic analysis of four Basque families.</strong>
Ann. Neurol. 57: 365-372, 2005.
[PubMed: 15732106]
[Full Text: https://doi.org/10.1002/ana.20391]
</p>
</li>
<li>
<p class="mim-text-font">
Rajput, A., Dickson, D. W., Robinson, C. A., Ross, O. A., Dachsel, J. C., Lincoln, S. J., Cobb, S. A., Rajput, M. L., Farrer, M. J.
<strong>Parkinsonism, Lrrk2 G2019S, and tau neuropathology</strong>
Neurology 67: 1506-1508, 2006.
[PubMed: 17060589]
[Full Text: https://doi.org/10.1212/01.wnl.0000240220.33950.0c]
</p>
</li>
<li>
<p class="mim-text-font">
Ross, O. A., Toft, M., Whittle, A. J., Johnson, J. L., Papapetropoulos, S., Mash, D. C., Litvan, I., Gordon, M. F., Wszolek, Z. K., Farrer, M. J., Dickson, D. W.
<strong>Lrrk2 and Lewy body disease.</strong>
Ann. Neurol. 59: 388-393, 2006.
[PubMed: 16437559]
[Full Text: https://doi.org/10.1002/ana.20731]
</p>
</li>
<li>
<p class="mim-text-font">
Satake, W., Nakabayashi, Y., Mizuta, I., Hirota, Y., Ito, C., Kubo, M., Kawaguchi, T., Tsunoda, T., Watanabe, M., Takeda, A., Tomiyama, H., Nakashima, K., and 10 others.
<strong>Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson&#x27;s disease. (Letter)</strong>
Nature Genet. 41: 1303-1307, 2009.
[PubMed: 19915576]
[Full Text: https://doi.org/10.1038/ng.485]
</p>
</li>
<li>
<p class="mim-text-font">
Saunders-Pullman, R., Stanley, K., Wang, C., San Luciano, M., Shanker, V., Hunt, A., Severt, L., Raymond, D., Ozelius, L. J., Lipton, R. B., Bressman, S. B.
<strong>Olfactory dysfunction in LRRK2 G2019S mutation carriers.</strong>
Neurology 77: 319-324, 2011.
[PubMed: 21753159]
[Full Text: https://doi.org/10.1212/WNL.0b013e318227041c]
</p>
</li>
<li>
<p class="mim-text-font">
Silveira-Moriyama, L., Guedes, L. C., Kingsbury, A., Ayling, H., Shaw, K., Barbosa, E. R., Bonifati, V., Quinn, N. P., Abou-Sleiman, P., Wood, N. W., Petrie, A., Sampaio, C., Ferreira, J. J., Holton, J., Revesz, T., Lees, A. J.
<strong>Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data.</strong>
Neurology 71: 1021-1026, 2008.
[PubMed: 18809839]
[Full Text: https://doi.org/10.1212/01.wnl.0000326575.20829.45]
</p>
</li>
<li>
<p class="mim-text-font">
Skipper, L., Li, Y., Bonnard, C., Pavanni, R., Yih, Y., Chua, E., Sung, W.-K., Tan, L., Wong, M.-C., Tan, E.-K., Liu, J.
<strong>Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson&#x27;s disease.</strong>
Hum. Molec. Genet. 14: 3549-3556, 2005.
[PubMed: 16269443]
[Full Text: https://doi.org/10.1093/hmg/ddi376]
</p>
</li>
<li>
<p class="mim-text-font">
Tan, E.-K., Kwok, H.-H., Tan, L. C., Zhao, W.-T., Prakash, K. M., Au, W.-L., Pavanni, R., Ng, Y.-Y., Satake, W., Zhao, Y., Toda, T., Liu, J.-J.
<strong>Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus.</strong>
Neurology 75: 508-512, 2010. Note: Erratum: Neurology 75: 1399 only, 2010.
[PubMed: 20697102]
[Full Text: https://doi.org/10.1212/WNL.0b013e3181eccfcd]
</p>
</li>
<li>
<p class="mim-text-font">
Wszolek, Z. K., Pfeiffer, B., Fulgham, J. R., Parisi, J. E., Thompson, B. M., Uitti, R. J., Calne, D. B., Pfeiffer, R. F.
<strong>Western Nebraska family (family D) with autosomal dominant parkinsonism.</strong>
Neurology 45: 502-505, 1995.
[PubMed: 7898705]
[Full Text: https://doi.org/10.1212/wnl.45.3.502]
</p>
</li>
<li>
<p class="mim-text-font">
Wszolek, Z. K., Pfeiffer, R. F., Tsuboi, Y., Uitti, R. J., McComb, R. D., Stoessl, A. J., Strongosky, A. J., Zimprich, A., Muller-Myhsok, B., Farrer, M. J., Gasser, T., Calne, D. B., Dickson, D. W.
<strong>Autosomal dominant parkinsonism associated with variable synuclein and tau pathology.</strong>
Neurology 62: 1619-1622, 2004.
[PubMed: 15136696]
[Full Text: https://doi.org/10.1212/01.wnl.0000125015.06989.db]
</p>
</li>
<li>
<p class="mim-text-font">
Zhu, X., Siedlak, S. L., Smith, M. A., Perry, G., Chen, S. G.
<strong>LRRK2 protein is a component of Lewy bodies. (Letter)</strong>
Ann. Neurol. 60: 617-618, 2006.
[PubMed: 16847950]
[Full Text: https://doi.org/10.1002/ana.20928]
</p>
</li>
<li>
<p class="mim-text-font">
Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R. J., Calne, D. B., Stoessl, A. J., Pfeiffer, R. F., Patenge, N., Carballo Carbajal, I., Vieregge, P., Asmus, F., Muller-Myhsok, B., Dickson, D. W., Meitinger, T., Strom, T. M., Wszolek, Z. K., Gasser, T.
<strong>Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.</strong>
Neuron 44: 601-607, 2004.
[PubMed: 15541309]
[Full Text: https://doi.org/10.1016/j.neuron.2004.11.005]
</p>
</li>
<li>
<p class="mim-text-font">
Zimprich, A., Muller-Myhsok, Farrer, M., Leitner, P., Sharma, M., Hulihan, M., Lockhart, P., Strongosky, A., Kachergus, J., Calne, D. B., Stoessel, J., Uitti, R. J., and 9 others.
<strong>The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval.</strong>
Am. J. Hum. Genet. 74: 11-19, 2004. Note: Erratum: Am. J. Med. Genet. 75: 534 only, 2004.
[PubMed: 14691730]
[Full Text: https://doi.org/10.1086/380647]
</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 : 3/11/2013<br>Cassandra L. Kniffin - updated : 11/14/2011<br>Cassandra L. Kniffin - updated : 6/23/2011<br>Cassandra L. Kniffin - updated : 2/15/2011<br>Cassandra L. Kniffin - updated : 12/3/2010<br>Cassandra L. Kniffin - updated : 11/2/2010<br>Ada Hamosh - updated : 8/24/2010<br>Cassandra L. Kniffin - updated : 6/25/2010<br>Cassandra L. Kniffin - updated : 3/1/2010<br>Cassandra L. Kniffin - updated : 1/4/2010<br>Cassandra L. Kniffin - updated : 8/31/2009<br>George E. Tiller - updated : 4/23/2009<br>Cassandra L. Kniffin - updated : 3/16/2009<br>Cassandra L. Kniffin - updated : 1/9/2009<br>Cassandra L. Kniffin - updated : 10/28/2008<br>Cassandra L. Kniffin - updated : 5/28/2008<br>Cassandra L. Kniffin - updated : 4/2/2008<br>Cassandra L. Kniffin - updated : 3/13/2008<br>Cassandra L. Kniffin - updated : 9/12/2007<br>Cassandra L. Kniffin - updated : 11/6/2006<br>Cassandra L. Kniffin - updated : 4/20/2006<br>Cassandra L. Kniffin - updated : 11/7/2005<br>Cassandra L. Kniffin - updated : 8/26/2005<br>Cassandra L. Kniffin - updated : 5/11/2005<br>Cassandra L. Kniffin - updated : 2/9/2005<br>Cassandra L. Kniffin - updated : 11/2/2004<br>Victor A. McKusick - updated : 1/6/2004
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin : 6/24/2002
</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 : 11/03/2017<br>mcolton : 02/24/2014<br>alopez : 3/12/2013<br>alopez : 3/12/2013<br>ckniffin : 3/11/2013<br>terry : 5/24/2012<br>terry : 5/17/2012<br>carol : 11/16/2011<br>terry : 11/16/2011<br>ckniffin : 11/14/2011<br>wwang : 6/29/2011<br>ckniffin : 6/23/2011<br>wwang : 3/8/2011<br>ckniffin : 2/15/2011<br>carol : 1/28/2011<br>wwang : 12/6/2010<br>ckniffin : 12/3/2010<br>ckniffin : 11/17/2010<br>wwang : 11/2/2010<br>terry : 9/9/2010<br>mgross : 8/25/2010<br>terry : 8/24/2010<br>wwang : 6/29/2010<br>ckniffin : 6/25/2010<br>wwang : 3/4/2010<br>ckniffin : 3/1/2010<br>alopez : 1/4/2010<br>alopez : 1/4/2010<br>wwang : 9/11/2009<br>ckniffin : 8/31/2009<br>wwang : 5/13/2009<br>terry : 4/23/2009<br>wwang : 4/10/2009<br>ckniffin : 4/6/2009<br>wwang : 3/24/2009<br>ckniffin : 3/16/2009<br>wwang : 1/15/2009<br>ckniffin : 1/9/2009<br>wwang : 11/7/2008<br>ckniffin : 10/28/2008<br>wwang : 5/29/2008<br>ckniffin : 5/28/2008<br>wwang : 4/10/2008<br>ckniffin : 4/2/2008<br>wwang : 4/1/2008<br>ckniffin : 3/13/2008<br>wwang : 11/27/2007<br>wwang : 9/21/2007<br>ckniffin : 9/12/2007<br>wwang : 11/9/2006<br>ckniffin : 11/6/2006<br>carol : 6/21/2006<br>wwang : 4/25/2006<br>ckniffin : 4/20/2006<br>wwang : 11/15/2005<br>ckniffin : 11/7/2005<br>wwang : 9/6/2005<br>ckniffin : 8/26/2005<br>wwang : 5/18/2005<br>wwang : 5/13/2005<br>ckniffin : 5/11/2005<br>carol : 3/8/2005<br>tkritzer : 2/22/2005<br>ckniffin : 2/9/2005<br>ckniffin : 2/9/2005<br>carol : 11/2/2004<br>carol : 11/2/2004<br>ckniffin : 11/2/2004<br>carol : 8/26/2004<br>alopez : 3/17/2004<br>cwells : 1/7/2004<br>terry : 1/6/2004<br>carol : 6/26/2002<br>carol : 6/26/2002<br>ckniffin : 6/26/2002<br>ckniffin : 6/24/2002
</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>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</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>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</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">&times;</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>
Reference in a new issue View git blame Copy permalink