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<title>
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Entry
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- *129010 - EARLY GROWTH RESPONSE 2; EGR2
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- OMIM
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</ul>
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</nav>
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</div>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<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 />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</li>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</div>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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<span class="small">
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</form>
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<div class="row">
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<p />
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</div>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*129010</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/129010">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<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">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
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<div class="panel-body small mim-panel-body">
|
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|
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000122877;t=ENST00000242480" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=1959" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=129010" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000122877;t=ENST00000242480" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000399,NM_001136177,NM_001136178,NM_001136179,NM_001321037,NM_001410931" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000399" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=129010" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
|
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</span>
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</div>
|
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00551&isoform_id=00551_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/EGR2" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/181987,4581055,9845524,23272558,33112654,50833694,50833698,51476978,119574623,119574624,189053505,193787143,194384480,209969753,209969755,209969757,311643896,957949316,957949319,1005261237,2287780785,2462517347" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P11161" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
|
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</div>
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=1959" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000122877;t=ENST00000242480" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=EGR2" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=EGR2" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+1959" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/EGR2" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:1959" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1959" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr10&hgg_gene=ENST00000242480.4&hgg_start=62811996&hgg_end=62819167&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3239" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3239" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=129010[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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=129010[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000122877" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=EGR2" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=EGR2" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=EGR2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.molgen.ua.ac.be/CMTMutations/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=EGR2&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA27674" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:3239" 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>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:95296" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/EGR2#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:95296" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1959/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1959" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00007772;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00007772 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00043705;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00043705 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030723-6" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1959" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=EGR2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<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.">
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</span>
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</span>
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</div>
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<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">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 719979008<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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129010
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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EARLY GROWTH RESPONSE 2; EGR2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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KROX20
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=EGR2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EGR2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/10/230?start=-3&limit=10&highlight=230">10q21.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:62811996-62819167&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">10:62,811,996-62,819,167</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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Phenotype
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Phenotype <br /> MIM number
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10q21.3
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Charcot-Marie-Tooth disease, type 1D
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Dejerine-Sottas disease
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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Hypomyelinating neuropathy, congenital, 1
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<a href="/entry/605253"> 605253 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/129010" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/129010" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<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>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The EGR2 gene, a member of the early growth response gene family, encodes a transcription factor that is a prime regulator of Schwann cell myelination. It may also play a role in hindbrain segmentation and development (summary by <a href="#14" class="mim-tip-reference" title="Szigeti, K., Wiszniewski, W., Saifi, G. M., Sherman, D. L., Sule, N., Adesina, A. M., Mancias, P., Papasozomenos, S. C., Miller, G., Keppen, L., Daentl, D., Brophy, P. J., Lupski, J. R. <strong>Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.</strong> Neurogenetics 8: 257-262, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717711</a>] [<a href="https://doi.org/10.1007/s10048-007-0094-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17717711">Szigeti et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717711" 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>
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<strong>Cloning and Expression</strong>
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<p>Using low-stringency hybridization with an EGR1 (<a href="/entry/128990">128990</a>) cDNA probe, <a href="#5" class="mim-tip-reference" title="Joseph, L. J., Le Beau, M. M., Jamieson, G. A., Jr., Acharya, S., Shows, T. B., Rowley, J. D., Sukhatme, V. P. <strong>Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with 'zinc-binding finger' structure.</strong> Proc. Nat. Acad. Sci. 85: 7164-7168, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 86: 515 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3140236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3140236</a>] [<a href="https://doi.org/10.1073/pnas.85.19.7164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3140236">Joseph et al. (1988)</a> identified a distinct human cDNA, designated EGR2 (early growth response gene-2). The cDNA sequence predicts a protein of 406 amino acids, including 3 tandem zinc fingers of the cys(2)-his(2) class. The deduced amino acid sequences of human EGR2 and mouse Egr1 are 92% identical in the zinc finger region but show no similarity elsewhere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3140236" 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="Chavrier, P., Janssen-Timmen, U., Mattei, M.-G., Zerial, M., Bravo, R., Charnay, P. <strong>Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.</strong> Molec. Cell. Biol. 9: 787-797, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2496302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2496302</a>] [<a href="https://doi.org/10.1128/mcb.9.2.787-797.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2496302">Chavrier et al. (1989)</a> showed that alternative splicing of the most 5-prime intron of the Krox20 gene in mouse gives rise to mRNAs encoding putative zinc finger proteins with different N termini. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2496302" 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>
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<a id="geneStructure" class="mim-anchor"></a>
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<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Gene Structure</strong>
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<p><a href="#2" class="mim-tip-reference" title="Chavrier, P., Janssen-Timmen, U., Mattei, M.-G., Zerial, M., Bravo, R., Charnay, P. <strong>Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.</strong> Molec. Cell. Biol. 9: 787-797, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2496302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2496302</a>] [<a href="https://doi.org/10.1128/mcb.9.2.787-797.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2496302">Chavrier et al. (1989)</a> determined that the mouse Krox20 gene contains 3 exons and spans approximately 80 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2496302" 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>
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<a id="mapping" class="mim-anchor"></a>
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<strong>Mapping</strong>
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<p>By a combination of Southern analysis of DNA from mouse-human somatic cell hybrids and in situ hybridization, <a href="#5" class="mim-tip-reference" title="Joseph, L. J., Le Beau, M. M., Jamieson, G. A., Jr., Acharya, S., Shows, T. B., Rowley, J. D., Sukhatme, V. P. <strong>Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with 'zinc-binding finger' structure.</strong> Proc. Nat. Acad. Sci. 85: 7164-7168, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 86: 515 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3140236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3140236</a>] [<a href="https://doi.org/10.1073/pnas.85.19.7164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3140236">Joseph et al. (1988)</a> mapped the EGR2 gene to 10q21-q22. <a href="#20" class="mim-tip-reference" title="Wu, J., Joseph, L., Sukhatme, V. P., Kidd, K. K. <strong>A HindIII polymorphism identified by the human early growth response gene 2 (EGR2) on chromosome 10.</strong> Nucleic Acids Res. 16: 11855 only, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2905450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2905450</a>] [<a href="https://doi.org/10.1093/nar/16.24.11855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2905450">Wu et al. (1988)</a> demonstrated a HindIII polymorphism of EGR2; using this polymorphism, they confirmed the localization of EGR2 on 10q. <a href="#2" class="mim-tip-reference" title="Chavrier, P., Janssen-Timmen, U., Mattei, M.-G., Zerial, M., Bravo, R., Charnay, P. <strong>Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.</strong> Molec. Cell. Biol. 9: 787-797, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2496302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2496302</a>] [<a href="https://doi.org/10.1128/mcb.9.2.787-797.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2496302">Chavrier et al. (1989)</a> mapped the mouse gene, which they referred to as Krox20, to band B5 of chromosome 10 and the homologous human gene to human chromosome 10q21.1-q22.1, both by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3140236+2496302+2905450" 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>
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<p><a href="#5" class="mim-tip-reference" title="Joseph, L. J., Le Beau, M. M., Jamieson, G. A., Jr., Acharya, S., Shows, T. B., Rowley, J. D., Sukhatme, V. P. <strong>Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with 'zinc-binding finger' structure.</strong> Proc. Nat. Acad. Sci. 85: 7164-7168, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 86: 515 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3140236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3140236</a>] [<a href="https://doi.org/10.1073/pnas.85.19.7164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3140236">Joseph et al. (1988)</a> found that EGR2 is coregulated with EGR1 by fibroblast and lymphocyte mitogens; however, several stimuli that induce EGR1 mRNA in rat pheochromocytoma cells do not induce EGR2 mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3140236" 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="Chavrier, P., Janssen-Timmen, U., Mattei, M.-G., Zerial, M., Bravo, R., Charnay, P. <strong>Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.</strong> Molec. Cell. Biol. 9: 787-797, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2496302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2496302</a>] [<a href="https://doi.org/10.1128/mcb.9.2.787-797.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2496302">Chavrier et al. (1989)</a> showed that the first exon in mouse Egr2 contains a sequence element with strong similarity to the FOS (<a href="/entry/164810">164810</a>) protooncogene serum response element (SRE). This element can functionally substitute for the SRE of FOS and binds the same nuclear protein, which is likely SRF (<a href="/entry/600589">600589</a>). This SRE is probably responsible for the induction of Krox20 by serum, possibly in combination with the weaker SRE located in the 5-prime flanking region of the gene. FOS, Krox20, and a number of immediate-early serum response genes appear to be coregulated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2496302" 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 microarray expression profiling, <a href="#10" class="mim-tip-reference" title="Nagarajan, R., Svaren, J., Le, N., Araki, T., Watson, M., Milbrandt, J. <strong>EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.</strong> Neuron 30: 355-368, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11394999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11394999</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00282-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11394999">Nagarajan et al. (2001)</a> identified 98 known genes that were induced by Egr2 in Schwann cells. The putative Egr2 target genes included myelin proteins and enzymes required for synthesis of normal myelin lipids. Using RT-PCR to monitor Schwann cell gene expression, <a href="#10" class="mim-tip-reference" title="Nagarajan, R., Svaren, J., Le, N., Araki, T., Watson, M., Milbrandt, J. <strong>EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.</strong> Neuron 30: 355-368, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11394999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11394999</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00282-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11394999">Nagarajan et al. (2001)</a> confirmed that Egr2 is sufficient for induction of target genes including MPZ (<a href="/entry/159440">159440</a>), PMP22 (<a href="/entry/601097">601097</a>), MBP (<a href="/entry/159430">159430</a>), MAG (<a href="/entry/159460">159460</a>), CX32 (<a href="/entry/304040">304040</a>), and periaxin (<a href="/entry/605725">605725</a>). Using EGR2 DNA-binding domain mutants, <a href="#10" class="mim-tip-reference" title="Nagarajan, R., Svaren, J., Le, N., Araki, T., Watson, M., Milbrandt, J. <strong>EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.</strong> Neuron 30: 355-368, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11394999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11394999</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00282-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11394999">Nagarajan et al. (2001)</a> demonstrated a dominant-negative inhibition of wildtype Egr2-mediated induction of essential myelin genes. <a href="#10" class="mim-tip-reference" title="Nagarajan, R., Svaren, J., Le, N., Araki, T., Watson, M., Milbrandt, J. <strong>EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.</strong> Neuron 30: 355-368, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11394999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11394999</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00282-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11394999">Nagarajan et al. (2001)</a> observed that introduction of Egr2 into postnatal, Egr2-deficient Schwann cells is sufficient for induction of genes critical for myelination. They hypothesized that the normal function of Schwann cells in patients with inherited peripheral neuropathies attributed to mutations in EGR2 might be restored by reintroduction of EGR2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11394999" 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="#8" class="mim-tip-reference" title="Matsushima-Nishiu, M., Unoki, M., Ono, K., Tsunoda, T., Minaguchi, T., Kuramoto, H., Nishida, M., Satoh, T., Tanaka, T., Nakamura, Y. <strong>Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN.</strong> Cancer Res. 61: 3741-3749, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11325847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11325847</a>]" pmid="11325847">Matsushima-Nishiu et al. (2001)</a> analyzed expression profiles of cancer cells after the introduction of exogenous PTEN (<a href="/entry/601728">601728</a>), a tumor suppressor, and found that EGR2 was transcriptionally transactivated. <a href="#16" class="mim-tip-reference" title="Unoki, M., Nakamura, Y. <strong>Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.</strong> Oncogene 20: 4457-4465, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11494141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11494141</a>] [<a href="https://doi.org/10.1038/sj.onc.1204608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11494141">Unoki and Nakamura (2001)</a> showed that in colony formation assays, EGR2 was able to suppress the growth of cancer cells significantly. Antisense oligonucleotides for EGR2 effectively inhibited its expression, and cell growth was accelerated. <a href="#16" class="mim-tip-reference" title="Unoki, M., Nakamura, Y. <strong>Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.</strong> Oncogene 20: 4457-4465, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11494141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11494141</a>] [<a href="https://doi.org/10.1038/sj.onc.1204608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11494141">Unoki and Nakamura (2001)</a> suggested that EGR2 may mediate the growth suppressive effect of PTEN. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11325847+11494141" 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 microarray, RT-PCR, and computer analyses, <a href="#11" class="mim-tip-reference" title="Safford, M., Collins, S., Lutz, M. A., Allen, A., Huang, C.-T., Kowalski, J., Blackford, A., Horton, M. R., Drake, C., Schwartz, R. H., Powell, J. D. <strong>Egr-2 and Egr-3 are negative regulators of T cell activation.</strong> Nature Immun. 6: 472-480, 2005. Note: Erratum: Nature Immun. 6: 737 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15834410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15834410</a>] [<a href="https://doi.org/10.1038/ni1193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15834410">Safford et al. (2005)</a> found that Egr2 and Egr3 (<a href="/entry/602419">602419</a>) were associated with induction of anergy in mouse T cells, as measured by inhibition of Il2 (<a href="/entry/147680">147680</a>) production. Overexpression of Egr2 or Egr3 inhibited Il2 production equivalently. Although Egr2 -/- mice died perinatally, Egr3 -/- mice were resistant to peptide-induced immunologic tolerance. <a href="#11" class="mim-tip-reference" title="Safford, M., Collins, S., Lutz, M. A., Allen, A., Huang, C.-T., Kowalski, J., Blackford, A., Horton, M. R., Drake, C., Schwartz, R. H., Powell, J. D. <strong>Egr-2 and Egr-3 are negative regulators of T cell activation.</strong> Nature Immun. 6: 472-480, 2005. Note: Erratum: Nature Immun. 6: 737 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15834410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15834410</a>] [<a href="https://doi.org/10.1038/ni1193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15834410">Safford et al. (2005)</a> concluded that EGR2 and EGR3 are involved in promoting a T-cell receptor-induced negative regulatory genetic program. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15834410" 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="Kao, S.-C., Wu, H., Xie, J., Chang, C.-P., Ranish, J. A., Graef, I. A., Crabtree, G. R. <strong>Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation.</strong> Science 323: 651-654, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179536</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19179536[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1166562" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19179536">Kao et al. (2009)</a> found that mice lacking calcineurin B1 (CNB1; <a href="/entry/601302">601302</a>) in the neural crest had defects in Schwann cell differentiation and myelination. Neuregulin (NRG1; <a href="/entry/142445">142445</a>) addition to Schwann cell precursors initiated an increase in cytoplasmic calcium ion, which activates calcineurin and the downstream transcription factors Nfatc3 (<a href="/entry/602698">602698</a>) and Nfatc4 (<a href="/entry/602699">602699</a>). Purification of Nfat protein complexes showed that Sox10 (<a href="/entry/602229">602229</a>) is an Nfat nuclear partner and synergizes with Nfatc4 to activate Krox20, which regulates genes necessary for myelination. <a href="#6" class="mim-tip-reference" title="Kao, S.-C., Wu, H., Xie, J., Chang, C.-P., Ranish, J. A., Graef, I. A., Crabtree, G. R. <strong>Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation.</strong> Science 323: 651-654, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179536</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19179536[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1166562" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19179536">Kao et al. (2009)</a> concluded that calcineurin and NFAT are essential for neuregulin and ErbB (see <a href="/entry/131550">131550</a>) signaling, neural crest diversification, and differentiation of Schwann cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Swanberg, S. E., Nagarajan, R. P., Peddada, S., Yasui, D. H., LaSalle, J. M. <strong>Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism.</strong> Hum. Molec. Genet. 18: 525-534, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19000991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19000991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19000991[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19000991">Swanberg et al. (2009)</a> showed by chromatin immunoprecipitation analysis that EGR2 bound to the MECP2 (<a href="/entry/300005">300005</a>) promoter and that MeCP2 bound to the intron 1 enhancer region of EGR2. Reduction in EGR2 and MeCP2 levels in cultured human neuroblastoma cells by RNAi reciprocally reduced expression of both EGR2 and MECP2 and their protein products. Mecp2-deficient mouse cortex samples showed significantly reduced EGR2 by quantitative immunofluorescence. Furthermore, MeCP2 and EGR2 showed coordinately increased levels during postnatal development of both mouse and human cortex. In contrast to age-matched controls, Rett syndrome (<a href="/entry/312750">312750</a>) and autism (<a href="/entry/209850">209850</a>) postmortem cortex samples showed significant reduction in EGR2. <a href="#13" class="mim-tip-reference" title="Swanberg, S. E., Nagarajan, R. P., Peddada, S., Yasui, D. H., LaSalle, J. M. <strong>Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism.</strong> Hum. Molec. Genet. 18: 525-534, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19000991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19000991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19000991[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19000991">Swanberg et al. (2009)</a> proposed a role of dysregulation of an activity-dependent EGR2/MeCP2 pathway in Rett syndrome and autism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19000991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Ghislain, J., Desmarquet-Trin-Dinh, C., Jaegle, M., Meijer, D., Charnay, P., Frain, M. <strong>Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development.</strong> Development 129: 155-166, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11782409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11782409</a>] [<a href="https://doi.org/10.1242/dev.129.1.155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11782409">Ghislain et al. (2002)</a> identified 2 cis-acting elements that regulated Krox20 expression in mouse Schwann cells. Immature Schwann cell element (ISE), located in an upstream region, was active in immature Schwann cells from their appearance at 15.5 days postcoitum until birth. In contrast, myelinating Schwann cell element (MSE; <a href="/entry/614996">614996</a>), a 1.3-kb element located 35 kb downstream of the Krox20 gene, was active at the onset of myelination and in mature myelinating Schwann cells of adult mice. Both MSE and ISE were reactivated following nerve degeneration/regeneration in mice. MSE and ISE reactivation required Oct6 (POU3F1; <a href="/entry/602479">602479</a>) and an unidentified axon-dependent signal. Reactivation did not require Krox20, indicating that an autoregulatory mechanism was not required for their activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11782409" 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 stimulating T cells from mice with a conditional knockout of Egr2, <a href="#9" class="mim-tip-reference" title="Miao, T., Raymond, M., Bhullar, P., Ghaffari, E., Symonds, A. L. J., Meier, U. C., Giovannoni, G., Li, S., Wang, P. <strong>Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf.</strong> J. Immun. 190: 58-65, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23203924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23203924</a>] [<a href="https://doi.org/10.4049/jimmunol.1200868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23203924">Miao et al. (2013)</a> observed high induction of Il1 (see <a href="/entry/147720">147720</a>), Il17 (<a href="/entry/603149">603149</a>), and Il21 (<a href="/entry/605384">605384</a>), but not Il2 or Ifng (<a href="/entry/147570">147570</a>). Egr2, but not Egr1 or Egr3, was induced in naive mouse T cells by the Th17-cell inducers Tgfb (<a href="/entry/190180">190180</a>) and Il6 (<a href="/entry/147620">147620</a>), but not by Ifng or Il4 (<a href="/entry/147780">147780</a>), which promote Th1 and Th2 cells, respectively. Although expression of Th17 regulatory factors was not affected in Egr2-deficient Th17 cells, binding of Batf (<a href="/entry/612476">612476</a>) to DNA-binding sites in the Il17 promoters was significantly increased in Egr2-deficient Th17 cells. Mice lacking Egr2 were susceptible to induction of experimental autoimmune encephalomyelitis. Stimulated CD4 T cells from patients with multiple sclerosis (<a href="/entry/126200">126200</a>) showed normal expression of BATF, significantly reduced expression of EGR2, and increased expression of IL17. <a href="#9" class="mim-tip-reference" title="Miao, T., Raymond, M., Bhullar, P., Ghaffari, E., Symonds, A. L. J., Meier, U. C., Giovannoni, G., Li, S., Wang, P. <strong>Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf.</strong> J. Immun. 190: 58-65, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23203924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23203924</a>] [<a href="https://doi.org/10.4049/jimmunol.1200868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23203924">Miao et al. (2013)</a> concluded that EGR2 is involved in regulation of Th17 cytokine production and Th17 differentiation by inhibiting BATF function and that EGR2 is important in the control of autoimmunity and inflammation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23203924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Liao, C.-P., Booker, R. C., Morrison, S. J., Le, L. Q. <strong>Identification of hair shaft progenitors that create a niche for hair pigmentation.</strong> Genes Dev. 31: 744-756, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28465357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28465357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28465357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.298703.117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28465357">Liao et al. (2017)</a> found that mice with conditional deletion of Scf (KITLG; <a href="/entry/184745">184745</a>) in Krox20 lineage cells exhibited progressive hair graying and lost all hair pigmentation early in life, suggesting that Krox20 lineage cells were the main source of Scf for follicular melanocytes to produce hair pigment. Depletion of Scf in epithelial cells of mice completely abolished hair pigmentation. Lacz reporter analysis suggested that hair pigmentation was regulated by Scf expression in hair shaft progenitor cells in the hair matrix. These hair shaft progenitors in the matrix were differentiated from follicular epithelial cells expressing Krox20. <a href="#7" class="mim-tip-reference" title="Liao, C.-P., Booker, R. C., Morrison, S. J., Le, L. Q. <strong>Identification of hair shaft progenitors that create a niche for hair pigmentation.</strong> Genes Dev. 31: 744-756, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28465357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28465357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28465357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.298703.117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28465357">Liao et al. (2017)</a> concluded that their study delineated the origin of SCF expression in hair matrix progenitors as a niche for follicular mature melanocytes and that their SCF is indispensible for hair pigmentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28465357" 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>
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<p><strong><em>Congenital Hypomyelinating Neuropathy 1</em></strong></p><p>
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Warner et al. (<a href="#18" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I., Lupski, J. R. <strong>Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A350 only, 1997."None>1997</a>, <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">1998</a>) hypothesized that Krox20 may be a transcription factor affecting late myelin genes. Using heteroduplex analysis for a mutational screen on 22 patients diagnosed with a severe peripheral neuropathy, 1 was found to have a mutation in the EGR2 gene. The patient was part of a family in which 3 sibs had congenital hypomyelinating neuropathy-1 (CHN1; <a href="/entry/605253">605253</a>) and the parents were first cousins, consistent with autosomal recessive inheritance. All 3 affected sibs were homozygous for an ile268-to-asn missense mutation (<a href="#0001">129010.0001</a>). Both parents and an unaffected sib were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537424" 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>Charcot-Marie-Tooth Disease Type 1D</em></strong></p><p>
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<a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">Warner et al. (1998)</a> identified heterozygous mutations in the EGR2 gene (<a href="#0002">129010.0002</a>) in a family with autosomal dominant Charcot-Marie-Tooth disease type 1D (<a href="/entry/607678">607678</a>). They also identified heterozygosity for a double mutation in a de novo case of congenital hypomyelinating neuropathy, i.e., an autosomal dominant form of CHN (<a href="#0003">129010.0003</a>). <a href="#19" class="mim-tip-reference" title="Warner, L. E., Svaren, J., Milbrandt, J., Lupski, J. R. <strong>Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.</strong> Hum. Molec. Genet. 8: 1245-1251, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369870</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369870">Warner et al. (1999)</a> used a combination of DNA-binding assays and transcriptional analysis to identify the functional consequences of these mutations. They determined that the zinc finger mutations (<a href="#0002">129010.0002</a>-<a href="#0004">129010.0004</a>) affect DNA binding, and that the amount of residual binding directly correlates with disease severity. The R1 domain mutation (<a href="#0001">129010.0001</a>) prevents interaction of EGR2 with the NAB corepressors (see <a href="/entry/600800">600800</a>) and thereby increases transcriptional activity. The authors found that the results of the in vitro functional studies correlated well with the clinical severity of the myelinopathy phenotypes, providing insight into possible disease mechanisms responsible for the varying severity and differences in inheritance patterns. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537424+10369870" 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>Dejerine-Sottas Syndrome</em></strong></p><p>
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<a href="#15" class="mim-tip-reference" title="Timmerman, V., De Jonghe, P., Ceuterick, C., De Vriendt, E., Lofgren, A., Nelis, E., Warner, L. E., Lupski, J. R., Martin, J.-J., Van Broeckhoven, C. <strong>Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype.</strong> Neurology 52: 1827-1832, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10371530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10371530</a>] [<a href="https://doi.org/10.1212/wnl.52.9.1827" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10371530">Timmerman et al. (1999)</a> screened 170 unrelated neuropathy patients and identified 2 with Dejerine-Sottas neuropathy (DSS; <a href="/entry/145900">145900</a>) who had a heterozygous R359W mutation (<a href="#0004">129010.0004</a>) in the alpha-helix domain of the first zinc finger of EGR2. Sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibers, classic onion bulbs, and focally folded myelin sheaths. <a href="#1" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., Bacino, C. A., Daentl, D., Lupski, J. R. <strong>EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.</strong> Neurogenetics 3: 153-157, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11523566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11523566</a>] [<a href="https://doi.org/10.1007/s100480100107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11523566">Boerkoel et al. (2001)</a> reported 2 additional DSN patients with the R359W mutation and suggested that it is the most common neuropathy-associated EGR2 mutation and consistently causes DSN. The expressivity ranged from that typical for DSN to a more rapidly progressive neuropathy that can cause death by age 6 years. Furthermore, in contrast to patients with typical DSN, patients with the R359W EGR2 mutation had more respiratory compromise and cranial nerve involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11523566+10371530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of 10 patients with various neuropathies associated with EGR2 mutations, <a href="#14" class="mim-tip-reference" title="Szigeti, K., Wiszniewski, W., Saifi, G. M., Sherman, D. L., Sule, N., Adesina, A. M., Mancias, P., Papasozomenos, S. C., Miller, G., Keppen, L., Daentl, D., Brophy, P. J., Lupski, J. R. <strong>Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.</strong> Neurogenetics 8: 257-262, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717711</a>] [<a href="https://doi.org/10.1007/s10048-007-0094-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17717711">Szigeti et al. (2007)</a> found that 60% had cranial nerve dysfunction, 45% had restrictive pulmonary disease, and 20% had scoliosis. Most patients required crutches, a walker, or a wheelchair to be mobile. One of the patients with Dejerine-Sottas neuropathy had a de novo mutation (<a href="#0005">129010.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717711" 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>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between variation in the EGR2 gene and susceptibility to systemic lupus erythematosus, see <a href="/entry/152700">152700</a>.</p>
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<p>Congenital hypomyelinating neuropathy is characterized clinically by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities. Warner et al. (<a href="#18" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I., Lupski, J. R. <strong>Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A350 only, 1997."None>1997</a>, <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">1998</a>) noted that pathologic findings on sural nerve biopsies show hypomyelination of most or all fibers. Based on these findings, CHN is considered to be a result of congenital impairment in myelin formation. The disorder is inherited as an autosomal recessive. The EGR2 gene attracted the attention of Warner et al. (<a href="#18" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I., Lupski, J. R. <strong>Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A350 only, 1997."None>1997</a>, <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">1998</a>) as a potential candidate for CHN because of the expression and knockout phenotype of its mouse homolog, Krox20. Krox20, a member of a multigene family of zinc finger proteins, is thought to function as an immediate early protein with basal expression in selected neuronal populations of the central and peripheral nervous systems. Krox20 knockout mice showed disrupted hindbrain segmentation and development and a block of Schwann cells at an early stage of differentiation as evidenced by the fact that the expression of early myelin genes, such as myelin-associated glycoprotein (<a href="/entry/159460">159460</a>), are barely affected while the expression of the late myelin genes, myelin basic protein (<a href="/entry/159430">159430</a>) and myelin protein zero (MPZ; <a href="/entry/159440">159440</a>), are decreased or absent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537424" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894158 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894158;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>Warner et al. (<a href="#18" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I., Lupski, J. R. <strong>Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A350 only, 1997."None>1997</a>, <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">1998</a>) demonstrated that 3 sibs, born of first-cousin parents (family HOU336), with congenital hypomyelinating neuropathy-1 (<a href="/entry/605253">605253</a>) were homozygous for a T-to-A transversion in the EGR2 gene that resulted in what they referred to as an ile218-to-asn amino acid substitution in the gene product. This mutation was later corrected by <a href="#19" class="mim-tip-reference" title="Warner, L. E., Svaren, J., Milbrandt, J., Lupski, J. R. <strong>Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.</strong> Hum. Molec. Genet. 8: 1245-1251, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369870</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369870">Warner et al. (1999)</a> and referred to as ile268 to asn (I268N). The mutation occurred at an inhibitory domain, which may result in dysregulation of EGR2 and an increase in transcriptional activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537424+10369870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Szigeti, K., Wiszniewski, W., Saifi, G. M., Sherman, D. L., Sule, N., Adesina, A. M., Mancias, P., Papasozomenos, S. C., Miller, G., Keppen, L., Daentl, D., Brophy, P. J., Lupski, J. R. <strong>Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.</strong> Neurogenetics 8: 257-262, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717711</a>] [<a href="https://doi.org/10.1007/s10048-007-0094-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17717711">Szigeti et al. (2007)</a> found almost complete absence of the myelin sheath from nerve fibers in 1 of the patients reported by <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">Warner et al. (1998)</a>. The I268N substitution occurs in the NAB repressor binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537424+17717711" 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>
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<strong>.0002 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1D</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894159 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894159;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018234 OR RCV001049422 OR RCV003482227" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018234, RCV001049422, RCV003482227" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018234...</a>
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<p>In a family (HOU184) in which the proband, his mother, and his half sister had demyelinating Charcot-Marie-Tooth disease type 1D (CMT1D; <a href="/entry/607678">607678</a>), <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">Warner et al. (1998)</a> found that affected members had a heterozygous C-to-T transition in the EGR2 gene that predicted an arg409-to-trp (R409W) substitution within the third zinc finger of the protein. CMT1 was diagnosed in the proband at age 15 years. His mother had been diagnosed at the age of 37 years, but described her initial symptoms as occurring during her first pregnancy at age 18 years. Nerve conduction velocities were markedly slowed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The form of Charcot-Marie-Tooth disease type 1 caused by mutations in the EGR2 gene was referred to by <a href="#12" class="mim-tip-reference" title="Street, V. A., Bennett, C. L., Goldy, J. D., Shirk, A. J., Kleopa, K. A., Tempel, B. L., Lipe, H. P., Scherer, S. S., Bird, T. D., Chance, P. F. <strong>Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C.</strong> Neurology 60: 22-26, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525712</a>] [<a href="https://doi.org/10.1212/wnl.60.1.22" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12525712">Street et al. (2003)</a> as CMT1D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525712" 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>
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<strong>.0003 NEUROPATHY, CONGENITAL HYPOMYELINATING, 1, AUTOSOMAL DOMINANT (1 patient)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894160 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894160;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs281865138 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865138;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281865138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient (family HOU431, patient 1085) with infantile hypotonia and gross motor developmental delay with ambulation after 2 years of age (see <a href="/entry/605253">605253</a>), <a href="#17" class="mim-tip-reference" title="Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R. <strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong> Nature Genet. 18: 382-384, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>] [<a href="https://doi.org/10.1038/ng0498-382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537424">Warner et al. (1998)</a> found de novo heterozygous mutations at consecutive nucleotides in the EGR2 gene, a T-to-G transversion and a G-to-T transversion, predicted to cause ser382-to-arg (S382R) and asp383-to-tyr (D383Y) substitutions within the second zinc finger of the protein. The mutations occurred in cis. Sequencing of cloned PCR products demonstrated that the mutations occurred on the same DNA strand. Both parents (99.5% probability of paternity by DNA tests) were wildtype, indicating that the patient represented a new mutation. At 7 years of age she was hypotonic generally and her muscle bulk was diminished, more distally than proximally. Her strength was also more impaired distally. She ambulated with a walker and ankle-foot orthotics for bilateral foot drop. Electrophysiologic studies showed marked abnormalities with absent sural, ulnar, and median sensory responses, low compound muscle action potential amplitudes, and markedly delayed distal latencies. Conduction velocities were markedly slowed. Light microscopic and enzyme histochemical analysis of a sural nerve biopsy showed profound absence or loss of myelin in virtually all axons and only 2 or 3 normally myelinated axons within the entire cross-section of the nerve. Axons were relatively preserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537424" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894161 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894161;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018236 OR RCV000018237 OR RCV000032120 OR RCV000231023 OR RCV000498897 OR RCV000856959" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018236, RCV000018237, RCV000032120, RCV000231023, RCV000498897, RCV000856959" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018236...</a>
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<a href="#1" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., Bacino, C. A., Daentl, D., Lupski, J. R. <strong>EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.</strong> Neurogenetics 3: 153-157, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11523566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11523566</a>] [<a href="https://doi.org/10.1007/s100480100107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11523566">Boerkoel et al. (2001)</a> reported 2 patients with Dejerine-Sottas neuropathy (<a href="/entry/145900">145900</a>) and an arg359-to-trp (R359W) mutation in the EGR2 gene. In both patients, the mutation appeared to be de novo dominant. One patient presented with hypotonia and hip dysplasia immediately after birth. She gained minimal use of her hands and feet during the first 6 months of life and then gradually lost motor function, developing paralysis distal to the knees and elbows by 2 years of age. A sural nerve biopsy demonstrated a marked decrease of myelinated fibers, evidence of demyelination and remyelination, and onion bulb formation. The course of her disease was characterized by increasing difficulty swallowing and breathing, and she died of respiratory failure at 6 years of age. The other patient had difficulty grasping objects and strabismus secondary to lateral recti weakness by 4 to 5 months of age. At 3 years of age, she had severe distal muscle weakness and atrophy, areflexia, and decreased pain and temperature sensation; in the lower extremities, she had less severe distal muscle weakness and atrophy, hyporeflexia, and intact sensation. As a complication of her hand involvement, she developed bilateral fixed contractures of the fourth and fifth fingers by 15 years of age. At 3 years of age nerve conduction velocities could not be measured in the median and ulnar nerve, but tibial nerve conduction velocity was 8 m/s. Sural nerve biopsy showed typical changes of DSN, including onion bulb formation. She developed severe thoracolumbar scoliosis, requiring spinal fusion at 15 years of age. At age 22 years she was following a rigorous physical exercise program, including weight lifting and walking on a treadmill, and she had completed a university education. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11523566" 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>Charcot-Marie-Tooth Disease, Demyelinating, Type 1D</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Chung, K. W., Sunwoo, I. N., Kim, S. M., Park, K. D., Kim, W.-K., Kim, T. S., Koo, H., Cho, M., Lee, J., Choi, B. O. <strong>Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family.</strong> Neurogenetics 6: 159-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15947997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15947997</a>] [<a href="https://doi.org/10.1007/s10048-005-0217-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15947997">Chung et al. (2005)</a> identified a heterozygous R359W mutation in the ERG2 gene in a Korean father with Charcot-Marie-Tooth disease type 1D (CMT1D; <a href="/entry/607678">607678</a>) and a daughter with Dejerine-Sottas syndrome. In addition, the daughter was found to have a de novo mutation in the GJB1 gene (V136A; <a href="/entry/304040#0021">304040.0021</a>). The father had pes cavus and developed difficulty walking at age 8 years, but had a milder phenotype than the daughter, who had experienced gait difficulties since infancy and facial weakness. She also had bilateral hand muscle weakness and atrophy and had sensory impairment of both upper and lower extremities. <a href="#19" class="mim-tip-reference" title="Warner, L. E., Svaren, J., Milbrandt, J., Lupski, J. R. <strong>Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.</strong> Hum. Molec. Genet. 8: 1245-1251, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369870</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369870">Warner et al. (1999)</a> had shown that the R359W substitution occurs in the first zinc finger domain and results in very low DNA-binding activity as well as decreased transcriptional activity of GJB1, resulting in abnormal myelination. <a href="#3" class="mim-tip-reference" title="Chung, K. W., Sunwoo, I. N., Kim, S. M., Park, K. D., Kim, W.-K., Kim, T. S., Koo, H., Cho, M., Lee, J., Choi, B. O. <strong>Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family.</strong> Neurogenetics 6: 159-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15947997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15947997</a>] [<a href="https://doi.org/10.1007/s10048-005-0217-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15947997">Chung et al. (2005)</a> concluded that the more severe phenotype in the daughter was caused by an additive effect of the 2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15947997+10369870" 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>
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<strong>.0005 DEJERINE-SOTTAS NEUROPATHY, AUTOSOMAL DOMINANT</strong>
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EGR2, GLU412LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434563 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434563;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121434563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018238 OR RCV001233037 OR RCV003447084" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018238, RCV001233037, RCV003447084" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018238...</a>
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<p>In a patient with Dejerine-Sottas neuropathy (<a href="/entry/145900">145900</a>), <a href="#14" class="mim-tip-reference" title="Szigeti, K., Wiszniewski, W., Saifi, G. M., Sherman, D. L., Sule, N., Adesina, A. M., Mancias, P., Papasozomenos, S. C., Miller, G., Keppen, L., Daentl, D., Brophy, P. J., Lupski, J. R. <strong>Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.</strong> Neurogenetics 8: 257-262, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717711</a>] [<a href="https://doi.org/10.1007/s10048-007-0094-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17717711">Szigeti et al. (2007)</a> identified a de novo heterozygous 1234G-A transition in the EGR2 gene, resulting in a glu412-to-lys (E412K) substitution in the third zinc finger domain. The patient had onset in infancy, delayed walking, cranial neuropathies, decreased motor nerve conduction velocities, and restrictive pulmonary disease. In vitro functional expression studies showed that the E412K mutant protein had about 28% transcriptional activity compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717711" 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>
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<strong>REFERENCES</strong>
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<a id="Boerkoel2001" class="mim-anchor"></a>
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Boerkoel, C. F., Takashima, H., Bacino, C. A., Daentl, D., Lupski, J. R.
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<strong>EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.</strong>
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Neurogenetics 3: 153-157, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11523566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11523566</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11523566" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s100480100107" target="_blank">Full Text</a>]
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<a id="Chavrier1989" class="mim-anchor"></a>
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Chavrier, P., Janssen-Timmen, U., Mattei, M.-G., Zerial, M., Bravo, R., Charnay, P.
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<strong>Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2496302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2496302</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2496302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/mcb.9.2.787-797.1989" target="_blank">Full Text</a>]
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Chung, K. W., Sunwoo, I. N., Kim, S. M., Park, K. D., Kim, W.-K., Kim, T. S., Koo, H., Cho, M., Lee, J., Choi, B. O.
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<strong>Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family.</strong>
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Neurogenetics 6: 159-163, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15947997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15947997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15947997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10048-005-0217-4" target="_blank">Full Text</a>]
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<a id="Ghislain2002" class="mim-anchor"></a>
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Ghislain, J., Desmarquet-Trin-Dinh, C., Jaegle, M., Meijer, D., Charnay, P., Frain, M.
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<strong>Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11782409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11782409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11782409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1242/dev.129.1.155" target="_blank">Full Text</a>]
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<a id="Joseph1988" class="mim-anchor"></a>
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Joseph, L. J., Le Beau, M. M., Jamieson, G. A., Jr., Acharya, S., Shows, T. B., Rowley, J. D., Sukhatme, V. P.
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<strong>Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with 'zinc-binding finger' structure.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3140236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3140236</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3140236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.85.19.7164" target="_blank">Full Text</a>]
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Kao, S.-C., Wu, H., Xie, J., Chang, C.-P., Ranish, J. A., Graef, I. A., Crabtree, G. R.
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<strong>Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation.</strong>
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Science 323: 651-654, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179536</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19179536[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=19179536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1166562" target="_blank">Full Text</a>]
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Liao, C.-P., Booker, R. C., Morrison, S. J., Le, L. Q.
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<strong>Identification of hair shaft progenitors that create a niche for hair pigmentation.</strong>
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Genes Dev. 31: 744-756, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28465357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28465357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28465357[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=28465357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gad.298703.117" target="_blank">Full Text</a>]
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Matsushima-Nishiu, M., Unoki, M., Ono, K., Tsunoda, T., Minaguchi, T., Kuramoto, H., Nishida, M., Satoh, T., Tanaka, T., Nakamura, Y.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11325847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11325847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11325847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Miao, T., Raymond, M., Bhullar, P., Ghaffari, E., Symonds, A. L. J., Meier, U. C., Giovannoni, G., Li, S., Wang, P.
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<strong>Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23203924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23203924</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23203924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.4049/jimmunol.1200868" target="_blank">Full Text</a>]
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Nagarajan, R., Svaren, J., Le, N., Araki, T., Watson, M., Milbrandt, J.
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<strong>EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.</strong>
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Neuron 30: 355-368, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11394999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11394999</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11394999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(01)00282-3" target="_blank">Full Text</a>]
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Safford, M., Collins, S., Lutz, M. A., Allen, A., Huang, C.-T., Kowalski, J., Blackford, A., Horton, M. R., Drake, C., Schwartz, R. H., Powell, J. D.
|
|
<strong>Egr-2 and Egr-3 are negative regulators of T cell activation.</strong>
|
|
Nature Immun. 6: 472-480, 2005. Note: Erratum: Nature Immun. 6: 737 only, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15834410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15834410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15834410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ni1193" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Street2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Street, V. A., Bennett, C. L., Goldy, J. D., Shirk, A. J., Kleopa, K. A., Tempel, B. L., Lipe, H. P., Scherer, S. S., Bird, T. D., Chance, P. F.
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<strong>Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C.</strong>
|
|
Neurology 60: 22-26, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.60.1.22" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Swanberg2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Swanberg, S. E., Nagarajan, R. P., Peddada, S., Yasui, D. H., LaSalle, J. M.
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<strong>Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism.</strong>
|
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Hum. Molec. Genet. 18: 525-534, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19000991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19000991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19000991[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=19000991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddn380" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Szigeti2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Szigeti, K., Wiszniewski, W., Saifi, G. M., Sherman, D. L., Sule, N., Adesina, A. M., Mancias, P., Papasozomenos, S. C., Miller, G., Keppen, L., Daentl, D., Brophy, P. J., Lupski, J. R.
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<strong>Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.</strong>
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Neurogenetics 8: 257-262, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717711" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10048-007-0094-0" target="_blank">Full Text</a>]
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<a id="15" class="mim-anchor"></a>
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<a id="Timmerman1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Timmerman, V., De Jonghe, P., Ceuterick, C., De Vriendt, E., Lofgren, A., Nelis, E., Warner, L. E., Lupski, J. R., Martin, J.-J., Van Broeckhoven, C.
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<strong>Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype.</strong>
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Neurology 52: 1827-1832, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10371530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10371530</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10371530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.52.9.1827" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Unoki2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Unoki, M., Nakamura, Y.
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<strong>Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.</strong>
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Oncogene 20: 4457-4465, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11494141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11494141</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11494141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.onc.1204608" target="_blank">Full Text</a>]
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<a id="17" class="mim-anchor"></a>
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<a id="Warner1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R.
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<strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong>
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Nature Genet. 18: 382-384, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0498-382" target="_blank">Full Text</a>]
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<a id="18" class="mim-anchor"></a>
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<a id="Warner1997" class="mim-anchor"></a>
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<p class="mim-text-font">
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Warner, L. E., Mancias, P., Butler, I., Lupski, J. R.
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<strong>Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract)</strong>
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Am. J. Hum. Genet. 61 (suppl.): A350 only, 1997.
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<a id="19" class="mim-anchor"></a>
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<a id="Warner1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Warner, L. E., Svaren, J., Milbrandt, J., Lupski, J. R.
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<strong>Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.</strong>
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Hum. Molec. Genet. 8: 1245-1251, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/8.7.1245" target="_blank">Full Text</a>]
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Wu1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wu, J., Joseph, L., Sukhatme, V. P., Kidd, K. K.
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<strong>A HindIII polymorphism identified by the human early growth response gene 2 (EGR2) on chromosome 10.</strong>
|
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Nucleic Acids Res. 16: 11855 only, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2905450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2905450</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2905450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/nar/16.24.11855" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 08/01/2022
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<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">
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<span class="mim-text-font">
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Paul J. Converse - updated : 8/19/2013<br>Patricia A. Hartz - updated : 12/19/2012<br>George E. Tiller - updated : 7/31/2009<br>Ada Hamosh - updated : 3/10/2009<br>Cassandra L. Kniffin - updated : 11/27/2007<br>Paul J. Converse - updated : 5/5/2006<br>Cassandra L. Kniffin - updated : 11/9/2005<br>Carol A. Bocchini - updated : 12/2/2003<br>Victor A. McKusick - updated : 3/7/2003<br>Dawn Watkins-Chow - updated : 3/18/2002<br>Victor A. McKusick - updated : 8/27/2001<br>George E. Tiller - updated : 1/17/2000<br>Victor A. McKusick - updated : 3/27/1998<br>Victor A. McKusick - updated : 10/24/1997
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 10/12/1988
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/10/2024
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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alopez : 08/14/2024<br>alopez : 08/13/2024<br>alopez : 08/01/2022<br>carol : 11/27/2018<br>ckniffin : 11/20/2018<br>alopez : 08/26/2013<br>mgross : 8/19/2013<br>terry : 3/14/2013<br>carol : 12/20/2012<br>carol : 12/20/2012<br>terry : 12/19/2012<br>carol : 10/23/2012<br>terry : 5/29/2012<br>wwang : 8/14/2009<br>terry : 7/31/2009<br>alopez : 3/13/2009<br>terry : 3/10/2009<br>wwang : 12/4/2007<br>ckniffin : 11/27/2007<br>mgross : 5/5/2006<br>wwang : 11/30/2005<br>ckniffin : 11/30/2005<br>wwang : 11/22/2005<br>ckniffin : 11/9/2005<br>terry : 6/2/2004<br>tkritzer : 12/3/2003<br>carol : 12/2/2003<br>ckniffin : 5/15/2003<br>ckniffin : 4/29/2003<br>carol : 4/25/2003<br>ckniffin : 4/23/2003<br>ckniffin : 4/23/2003<br>ckniffin : 4/8/2003<br>terry : 3/7/2003<br>cwells : 2/11/2003<br>cwells : 5/15/2002<br>alopez : 3/18/2002<br>alopez : 3/18/2002<br>mcapotos : 12/19/2001<br>carol : 8/27/2001<br>carol : 9/12/2000<br>terry : 9/11/2000<br>alopez : 9/6/2000<br>alopez : 1/17/2000<br>terry : 12/2/1999<br>carol : 5/20/1999<br>psherman : 6/6/1998<br>alopez : 4/1/1998<br>terry : 4/1/1998<br>terry : 3/27/1998<br>terry : 3/26/1998<br>terry : 10/28/1997<br>alopez : 10/27/1997<br>terry : 10/24/1997<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>carol : 3/24/1989<br>root : 3/13/1989<br>root : 11/4/1988
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 129010
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<div>
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<h3>
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<span class="mim-font">
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EARLY GROWTH RESPONSE 2; EGR2
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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KROX20
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: EGR2</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 719979008;
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</span>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 10q21.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:62,811,996-62,819,167 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
|
<th>
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|
Location
|
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</th>
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<th>
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|
Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
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</th>
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<th>
|
|
Phenotype <br /> mapping key
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</th>
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</tr>
|
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</thead>
|
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<tbody>
|
|
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<tr>
|
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<td rowspan="3">
|
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<span class="mim-font">
|
|
10q21.3
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</span>
|
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</td>
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<td>
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|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, type 1D
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</span>
|
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</td>
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<td>
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|
<span class="mim-font">
|
|
607678
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|
</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
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</span>
|
|
</td>
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<td>
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|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
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|
|
|
|
|
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|
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|
|
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</tr>
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|
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|
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|
|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Dejerine-Sottas disease
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
145900
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
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</span>
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</td>
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</tr>
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<tr>
|
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<td>
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<span class="mim-font">
|
|
Hypomyelinating neuropathy, congenital, 1
|
|
</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
605253
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
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</tr>
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|
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|
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</tbody>
|
|
</table>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
|
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</span>
|
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</h4>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>The EGR2 gene, a member of the early growth response gene family, encodes a transcription factor that is a prime regulator of Schwann cell myelination. It may also play a role in hindbrain segmentation and development (summary by Szigeti et al., 2007). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using low-stringency hybridization with an EGR1 (128990) cDNA probe, Joseph et al. (1988) identified a distinct human cDNA, designated EGR2 (early growth response gene-2). The cDNA sequence predicts a protein of 406 amino acids, including 3 tandem zinc fingers of the cys(2)-his(2) class. The deduced amino acid sequences of human EGR2 and mouse Egr1 are 92% identical in the zinc finger region but show no similarity elsewhere. </p><p>Chavrier et al. (1989) showed that alternative splicing of the most 5-prime intron of the Krox20 gene in mouse gives rise to mRNAs encoding putative zinc finger proteins with different N termini. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>Chavrier et al. (1989) determined that the mouse Krox20 gene contains 3 exons and spans approximately 80 kb. </p>
|
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</span>
|
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By a combination of Southern analysis of DNA from mouse-human somatic cell hybrids and in situ hybridization, Joseph et al. (1988) mapped the EGR2 gene to 10q21-q22. Wu et al. (1988) demonstrated a HindIII polymorphism of EGR2; using this polymorphism, they confirmed the localization of EGR2 on 10q. Chavrier et al. (1989) mapped the mouse gene, which they referred to as Krox20, to band B5 of chromosome 10 and the homologous human gene to human chromosome 10q21.1-q22.1, both by in situ hybridization. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
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|
<p>Joseph et al. (1988) found that EGR2 is coregulated with EGR1 by fibroblast and lymphocyte mitogens; however, several stimuli that induce EGR1 mRNA in rat pheochromocytoma cells do not induce EGR2 mRNA. </p><p>Chavrier et al. (1989) showed that the first exon in mouse Egr2 contains a sequence element with strong similarity to the FOS (164810) protooncogene serum response element (SRE). This element can functionally substitute for the SRE of FOS and binds the same nuclear protein, which is likely SRF (600589). This SRE is probably responsible for the induction of Krox20 by serum, possibly in combination with the weaker SRE located in the 5-prime flanking region of the gene. FOS, Krox20, and a number of immediate-early serum response genes appear to be coregulated. </p><p>Using microarray expression profiling, Nagarajan et al. (2001) identified 98 known genes that were induced by Egr2 in Schwann cells. The putative Egr2 target genes included myelin proteins and enzymes required for synthesis of normal myelin lipids. Using RT-PCR to monitor Schwann cell gene expression, Nagarajan et al. (2001) confirmed that Egr2 is sufficient for induction of target genes including MPZ (159440), PMP22 (601097), MBP (159430), MAG (159460), CX32 (304040), and periaxin (605725). Using EGR2 DNA-binding domain mutants, Nagarajan et al. (2001) demonstrated a dominant-negative inhibition of wildtype Egr2-mediated induction of essential myelin genes. Nagarajan et al. (2001) observed that introduction of Egr2 into postnatal, Egr2-deficient Schwann cells is sufficient for induction of genes critical for myelination. They hypothesized that the normal function of Schwann cells in patients with inherited peripheral neuropathies attributed to mutations in EGR2 might be restored by reintroduction of EGR2. </p><p>Matsushima-Nishiu et al. (2001) analyzed expression profiles of cancer cells after the introduction of exogenous PTEN (601728), a tumor suppressor, and found that EGR2 was transcriptionally transactivated. Unoki and Nakamura (2001) showed that in colony formation assays, EGR2 was able to suppress the growth of cancer cells significantly. Antisense oligonucleotides for EGR2 effectively inhibited its expression, and cell growth was accelerated. Unoki and Nakamura (2001) suggested that EGR2 may mediate the growth suppressive effect of PTEN. </p><p>Using microarray, RT-PCR, and computer analyses, Safford et al. (2005) found that Egr2 and Egr3 (602419) were associated with induction of anergy in mouse T cells, as measured by inhibition of Il2 (147680) production. Overexpression of Egr2 or Egr3 inhibited Il2 production equivalently. Although Egr2 -/- mice died perinatally, Egr3 -/- mice were resistant to peptide-induced immunologic tolerance. Safford et al. (2005) concluded that EGR2 and EGR3 are involved in promoting a T-cell receptor-induced negative regulatory genetic program. </p><p>Kao et al. (2009) found that mice lacking calcineurin B1 (CNB1; 601302) in the neural crest had defects in Schwann cell differentiation and myelination. Neuregulin (NRG1; 142445) addition to Schwann cell precursors initiated an increase in cytoplasmic calcium ion, which activates calcineurin and the downstream transcription factors Nfatc3 (602698) and Nfatc4 (602699). Purification of Nfat protein complexes showed that Sox10 (602229) is an Nfat nuclear partner and synergizes with Nfatc4 to activate Krox20, which regulates genes necessary for myelination. Kao et al. (2009) concluded that calcineurin and NFAT are essential for neuregulin and ErbB (see 131550) signaling, neural crest diversification, and differentiation of Schwann cells. </p><p>Swanberg et al. (2009) showed by chromatin immunoprecipitation analysis that EGR2 bound to the MECP2 (300005) promoter and that MeCP2 bound to the intron 1 enhancer region of EGR2. Reduction in EGR2 and MeCP2 levels in cultured human neuroblastoma cells by RNAi reciprocally reduced expression of both EGR2 and MECP2 and their protein products. Mecp2-deficient mouse cortex samples showed significantly reduced EGR2 by quantitative immunofluorescence. Furthermore, MeCP2 and EGR2 showed coordinately increased levels during postnatal development of both mouse and human cortex. In contrast to age-matched controls, Rett syndrome (312750) and autism (209850) postmortem cortex samples showed significant reduction in EGR2. Swanberg et al. (2009) proposed a role of dysregulation of an activity-dependent EGR2/MeCP2 pathway in Rett syndrome and autism. </p><p>Ghislain et al. (2002) identified 2 cis-acting elements that regulated Krox20 expression in mouse Schwann cells. Immature Schwann cell element (ISE), located in an upstream region, was active in immature Schwann cells from their appearance at 15.5 days postcoitum until birth. In contrast, myelinating Schwann cell element (MSE; 614996), a 1.3-kb element located 35 kb downstream of the Krox20 gene, was active at the onset of myelination and in mature myelinating Schwann cells of adult mice. Both MSE and ISE were reactivated following nerve degeneration/regeneration in mice. MSE and ISE reactivation required Oct6 (POU3F1; 602479) and an unidentified axon-dependent signal. Reactivation did not require Krox20, indicating that an autoregulatory mechanism was not required for their activity. </p><p>By stimulating T cells from mice with a conditional knockout of Egr2, Miao et al. (2013) observed high induction of Il1 (see 147720), Il17 (603149), and Il21 (605384), but not Il2 or Ifng (147570). Egr2, but not Egr1 or Egr3, was induced in naive mouse T cells by the Th17-cell inducers Tgfb (190180) and Il6 (147620), but not by Ifng or Il4 (147780), which promote Th1 and Th2 cells, respectively. Although expression of Th17 regulatory factors was not affected in Egr2-deficient Th17 cells, binding of Batf (612476) to DNA-binding sites in the Il17 promoters was significantly increased in Egr2-deficient Th17 cells. Mice lacking Egr2 were susceptible to induction of experimental autoimmune encephalomyelitis. Stimulated CD4 T cells from patients with multiple sclerosis (126200) showed normal expression of BATF, significantly reduced expression of EGR2, and increased expression of IL17. Miao et al. (2013) concluded that EGR2 is involved in regulation of Th17 cytokine production and Th17 differentiation by inhibiting BATF function and that EGR2 is important in the control of autoimmunity and inflammation. </p><p>Liao et al. (2017) found that mice with conditional deletion of Scf (KITLG; 184745) in Krox20 lineage cells exhibited progressive hair graying and lost all hair pigmentation early in life, suggesting that Krox20 lineage cells were the main source of Scf for follicular melanocytes to produce hair pigment. Depletion of Scf in epithelial cells of mice completely abolished hair pigmentation. Lacz reporter analysis suggested that hair pigmentation was regulated by Scf expression in hair shaft progenitor cells in the hair matrix. These hair shaft progenitors in the matrix were differentiated from follicular epithelial cells expressing Krox20. Liao et al. (2017) concluded that their study delineated the origin of SCF expression in hair matrix progenitors as a niche for follicular mature melanocytes and that their SCF is indispensible for hair pigmentation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Hypomyelinating Neuropathy 1</em></strong></p><p>
|
|
Warner et al. (1997, 1998) hypothesized that Krox20 may be a transcription factor affecting late myelin genes. Using heteroduplex analysis for a mutational screen on 22 patients diagnosed with a severe peripheral neuropathy, 1 was found to have a mutation in the EGR2 gene. The patient was part of a family in which 3 sibs had congenital hypomyelinating neuropathy-1 (CHN1; 605253) and the parents were first cousins, consistent with autosomal recessive inheritance. All 3 affected sibs were homozygous for an ile268-to-asn missense mutation (129010.0001). Both parents and an unaffected sib were heterozygous for the mutation. </p><p><strong><em>Charcot-Marie-Tooth Disease Type 1D</em></strong></p><p>
|
|
Warner et al. (1998) identified heterozygous mutations in the EGR2 gene (129010.0002) in a family with autosomal dominant Charcot-Marie-Tooth disease type 1D (607678). They also identified heterozygosity for a double mutation in a de novo case of congenital hypomyelinating neuropathy, i.e., an autosomal dominant form of CHN (129010.0003). Warner et al. (1999) used a combination of DNA-binding assays and transcriptional analysis to identify the functional consequences of these mutations. They determined that the zinc finger mutations (129010.0002-129010.0004) affect DNA binding, and that the amount of residual binding directly correlates with disease severity. The R1 domain mutation (129010.0001) prevents interaction of EGR2 with the NAB corepressors (see 600800) and thereby increases transcriptional activity. The authors found that the results of the in vitro functional studies correlated well with the clinical severity of the myelinopathy phenotypes, providing insight into possible disease mechanisms responsible for the varying severity and differences in inheritance patterns. </p><p><strong><em>Dejerine-Sottas Syndrome</em></strong></p><p>
|
|
Timmerman et al. (1999) screened 170 unrelated neuropathy patients and identified 2 with Dejerine-Sottas neuropathy (DSS; 145900) who had a heterozygous R359W mutation (129010.0004) in the alpha-helix domain of the first zinc finger of EGR2. Sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibers, classic onion bulbs, and focally folded myelin sheaths. Boerkoel et al. (2001) reported 2 additional DSN patients with the R359W mutation and suggested that it is the most common neuropathy-associated EGR2 mutation and consistently causes DSN. The expressivity ranged from that typical for DSN to a more rapidly progressive neuropathy that can cause death by age 6 years. Furthermore, in contrast to patients with typical DSN, patients with the R359W EGR2 mutation had more respiratory compromise and cranial nerve involvement. </p><p>In a review of 10 patients with various neuropathies associated with EGR2 mutations, Szigeti et al. (2007) found that 60% had cranial nerve dysfunction, 45% had restrictive pulmonary disease, and 20% had scoliosis. Most patients required crutches, a walker, or a wheelchair to be mobile. One of the patients with Dejerine-Sottas neuropathy had a de novo mutation (129010.0005). </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variation in the EGR2 gene and susceptibility to systemic lupus erythematosus, see 152700.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Congenital hypomyelinating neuropathy is characterized clinically by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities. Warner et al. (1997, 1998) noted that pathologic findings on sural nerve biopsies show hypomyelination of most or all fibers. Based on these findings, CHN is considered to be a result of congenital impairment in myelin formation. The disorder is inherited as an autosomal recessive. The EGR2 gene attracted the attention of Warner et al. (1997, 1998) as a potential candidate for CHN because of the expression and knockout phenotype of its mouse homolog, Krox20. Krox20, a member of a multigene family of zinc finger proteins, is thought to function as an immediate early protein with basal expression in selected neuronal populations of the central and peripheral nervous systems. Krox20 knockout mice showed disrupted hindbrain segmentation and development and a block of Schwann cells at an early stage of differentiation as evidenced by the fact that the expression of early myelin genes, such as myelin-associated glycoprotein (159460), are barely affected while the expression of the late myelin genes, myelin basic protein (159430) and myelin protein zero (MPZ; 159440), are decreased or absent. </p>
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</span>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
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<strong>5 Selected Examples):</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 NEUROPATHY, CONGENITAL HYPOMYELINATING, 1, AUTOSOMAL RECESSIVE</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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EGR2, ILE268ASN
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<br />
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SNP: rs104894158,
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ClinVar: RCV000031897, RCV003447083
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Warner et al. (1997, 1998) demonstrated that 3 sibs, born of first-cousin parents (family HOU336), with congenital hypomyelinating neuropathy-1 (605253) were homozygous for a T-to-A transversion in the EGR2 gene that resulted in what they referred to as an ile218-to-asn amino acid substitution in the gene product. This mutation was later corrected by Warner et al. (1999) and referred to as ile268 to asn (I268N). The mutation occurred at an inhibitory domain, which may result in dysregulation of EGR2 and an increase in transcriptional activity. </p><p>Szigeti et al. (2007) found almost complete absence of the myelin sheath from nerve fibers in 1 of the patients reported by Warner et al. (1998). The I268N substitution occurs in the NAB repressor binding site. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
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<strong>.0002 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1D</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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EGR2, ARG409TRP
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<br />
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|
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SNP: rs104894159,
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ClinVar: RCV000018234, RCV001049422, RCV003482227
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a family (HOU184) in which the proband, his mother, and his half sister had demyelinating Charcot-Marie-Tooth disease type 1D (CMT1D; 607678), Warner et al. (1998) found that affected members had a heterozygous C-to-T transition in the EGR2 gene that predicted an arg409-to-trp (R409W) substitution within the third zinc finger of the protein. CMT1 was diagnosed in the proband at age 15 years. His mother had been diagnosed at the age of 37 years, but described her initial symptoms as occurring during her first pregnancy at age 18 years. Nerve conduction velocities were markedly slowed. </p><p>The form of Charcot-Marie-Tooth disease type 1 caused by mutations in the EGR2 gene was referred to by Street et al. (2003) as CMT1D. </p>
|
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</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NEUROPATHY, CONGENITAL HYPOMYELINATING, 1, AUTOSOMAL DOMINANT (1 patient)</strong>
|
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</span>
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</h4>
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</div>
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<div>
|
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<span class="mim-text-font">
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EGR2, SER382ARG AND ASP383TYR
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<br />
|
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|
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SNP: rs104894160, rs281865138,
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ClinVar: RCV000018235, RCV000032121, RCV000032122, RCV003447096, RCV003447097
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient (family HOU431, patient 1085) with infantile hypotonia and gross motor developmental delay with ambulation after 2 years of age (see 605253), Warner et al. (1998) found de novo heterozygous mutations at consecutive nucleotides in the EGR2 gene, a T-to-G transversion and a G-to-T transversion, predicted to cause ser382-to-arg (S382R) and asp383-to-tyr (D383Y) substitutions within the second zinc finger of the protein. The mutations occurred in cis. Sequencing of cloned PCR products demonstrated that the mutations occurred on the same DNA strand. Both parents (99.5% probability of paternity by DNA tests) were wildtype, indicating that the patient represented a new mutation. At 7 years of age she was hypotonic generally and her muscle bulk was diminished, more distally than proximally. Her strength was also more impaired distally. She ambulated with a walker and ankle-foot orthotics for bilateral foot drop. Electrophysiologic studies showed marked abnormalities with absent sural, ulnar, and median sensory responses, low compound muscle action potential amplitudes, and markedly delayed distal latencies. Conduction velocities were markedly slowed. Light microscopic and enzyme histochemical analysis of a sural nerve biopsy showed profound absence or loss of myelin in virtually all axons and only 2 or 3 normally myelinated axons within the entire cross-section of the nerve. Axons were relatively preserved. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 DEJERINE-SOTTAS NEUROPATHY, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1D, INCLUDED
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</span>
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<span class="mim-text-font">
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EGR2, ARG359TRP
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<br />
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SNP: rs104894161,
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ClinVar: RCV000018236, RCV000018237, RCV000032120, RCV000231023, RCV000498897, RCV000856959
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</span>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Dejerine-Sottas Neuropathy</em></strong></p><p>
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Boerkoel et al. (2001) reported 2 patients with Dejerine-Sottas neuropathy (145900) and an arg359-to-trp (R359W) mutation in the EGR2 gene. In both patients, the mutation appeared to be de novo dominant. One patient presented with hypotonia and hip dysplasia immediately after birth. She gained minimal use of her hands and feet during the first 6 months of life and then gradually lost motor function, developing paralysis distal to the knees and elbows by 2 years of age. A sural nerve biopsy demonstrated a marked decrease of myelinated fibers, evidence of demyelination and remyelination, and onion bulb formation. The course of her disease was characterized by increasing difficulty swallowing and breathing, and she died of respiratory failure at 6 years of age. The other patient had difficulty grasping objects and strabismus secondary to lateral recti weakness by 4 to 5 months of age. At 3 years of age, she had severe distal muscle weakness and atrophy, areflexia, and decreased pain and temperature sensation; in the lower extremities, she had less severe distal muscle weakness and atrophy, hyporeflexia, and intact sensation. As a complication of her hand involvement, she developed bilateral fixed contractures of the fourth and fifth fingers by 15 years of age. At 3 years of age nerve conduction velocities could not be measured in the median and ulnar nerve, but tibial nerve conduction velocity was 8 m/s. Sural nerve biopsy showed typical changes of DSN, including onion bulb formation. She developed severe thoracolumbar scoliosis, requiring spinal fusion at 15 years of age. At age 22 years she was following a rigorous physical exercise program, including weight lifting and walking on a treadmill, and she had completed a university education. </p><p><strong><em>Charcot-Marie-Tooth Disease, Demyelinating, Type 1D</em></strong></p><p>
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Chung et al. (2005) identified a heterozygous R359W mutation in the ERG2 gene in a Korean father with Charcot-Marie-Tooth disease type 1D (CMT1D; 607678) and a daughter with Dejerine-Sottas syndrome. In addition, the daughter was found to have a de novo mutation in the GJB1 gene (V136A; 304040.0021). The father had pes cavus and developed difficulty walking at age 8 years, but had a milder phenotype than the daughter, who had experienced gait difficulties since infancy and facial weakness. She also had bilateral hand muscle weakness and atrophy and had sensory impairment of both upper and lower extremities. Warner et al. (1999) had shown that the R359W substitution occurs in the first zinc finger domain and results in very low DNA-binding activity as well as decreased transcriptional activity of GJB1, resulting in abnormal myelination. Chung et al. (2005) concluded that the more severe phenotype in the daughter was caused by an additive effect of the 2 mutations. </p>
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 DEJERINE-SOTTAS NEUROPATHY, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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EGR2, GLU412LYS
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<br />
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SNP: rs121434563,
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ClinVar: RCV000018238, RCV001233037, RCV003447084
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with Dejerine-Sottas neuropathy (145900), Szigeti et al. (2007) identified a de novo heterozygous 1234G-A transition in the EGR2 gene, resulting in a glu412-to-lys (E412K) substitution in the third zinc finger domain. The patient had onset in infancy, delayed walking, cranial neuropathies, decreased motor nerve conduction velocities, and restrictive pulmonary disease. In vitro functional expression studies showed that the E412K mutant protein had about 28% transcriptional activity compared to wildtype. </p>
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</span>
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<strong>EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.</strong>
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Neurogenetics 3: 153-157, 2001.
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[PubMed: 11523566]
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[Full Text: https://doi.org/10.1007/s100480100107]
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<p class="mim-text-font">
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Chavrier, P., Janssen-Timmen, U., Mattei, M.-G., Zerial, M., Bravo, R., Charnay, P.
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<strong>Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.</strong>
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Molec. Cell. Biol. 9: 787-797, 1989.
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Chung, K. W., Sunwoo, I. N., Kim, S. M., Park, K. D., Kim, W.-K., Kim, T. S., Koo, H., Cho, M., Lee, J., Choi, B. O.
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<strong>Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family.</strong>
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Neurogenetics 6: 159-163, 2005.
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Ghislain, J., Desmarquet-Trin-Dinh, C., Jaegle, M., Meijer, D., Charnay, P., Frain, M.
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<strong>Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development.</strong>
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Joseph, L. J., Le Beau, M. M., Jamieson, G. A., Jr., Acharya, S., Shows, T. B., Rowley, J. D., Sukhatme, V. P.
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<strong>Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with 'zinc-binding finger' structure.</strong>
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Proc. Nat. Acad. Sci. 85: 7164-7168, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 86: 515 only, 1989.
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Kao, S.-C., Wu, H., Xie, J., Chang, C.-P., Ranish, J. A., Graef, I. A., Crabtree, G. R.
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<strong>Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation.</strong>
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Science 323: 651-654, 2009.
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[PubMed: 19179536]
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[Full Text: https://doi.org/10.1126/science.1166562]
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<p class="mim-text-font">
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Liao, C.-P., Booker, R. C., Morrison, S. J., Le, L. Q.
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<strong>Identification of hair shaft progenitors that create a niche for hair pigmentation.</strong>
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Genes Dev. 31: 744-756, 2017.
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[PubMed: 28465357]
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[Full Text: https://doi.org/10.1101/gad.298703.117]
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<p class="mim-text-font">
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Matsushima-Nishiu, M., Unoki, M., Ono, K., Tsunoda, T., Minaguchi, T., Kuramoto, H., Nishida, M., Satoh, T., Tanaka, T., Nakamura, Y.
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<strong>Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN.</strong>
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Cancer Res. 61: 3741-3749, 2001.
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[PubMed: 11325847]
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<p class="mim-text-font">
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Miao, T., Raymond, M., Bhullar, P., Ghaffari, E., Symonds, A. L. J., Meier, U. C., Giovannoni, G., Li, S., Wang, P.
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<strong>Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf.</strong>
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J. Immun. 190: 58-65, 2013.
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[PubMed: 23203924]
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[Full Text: https://doi.org/10.4049/jimmunol.1200868]
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<p class="mim-text-font">
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Nagarajan, R., Svaren, J., Le, N., Araki, T., Watson, M., Milbrandt, J.
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<strong>EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.</strong>
|
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Neuron 30: 355-368, 2001.
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[PubMed: 11394999]
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[Full Text: https://doi.org/10.1016/s0896-6273(01)00282-3]
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<p class="mim-text-font">
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Safford, M., Collins, S., Lutz, M. A., Allen, A., Huang, C.-T., Kowalski, J., Blackford, A., Horton, M. R., Drake, C., Schwartz, R. H., Powell, J. D.
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<strong>Egr-2 and Egr-3 are negative regulators of T cell activation.</strong>
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[PubMed: 15834410]
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[Full Text: https://doi.org/10.1038/ni1193]
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Street, V. A., Bennett, C. L., Goldy, J. D., Shirk, A. J., Kleopa, K. A., Tempel, B. L., Lipe, H. P., Scherer, S. S., Bird, T. D., Chance, P. F.
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<strong>Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C.</strong>
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Neurology 60: 22-26, 2003.
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[PubMed: 12525712]
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</p>
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<li>
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Swanberg, S. E., Nagarajan, R. P., Peddada, S., Yasui, D. H., LaSalle, J. M.
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<strong>Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism.</strong>
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Hum. Molec. Genet. 18: 525-534, 2009.
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[Full Text: https://doi.org/10.1093/hmg/ddn380]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Szigeti, K., Wiszniewski, W., Saifi, G. M., Sherman, D. L., Sule, N., Adesina, A. M., Mancias, P., Papasozomenos, S. C., Miller, G., Keppen, L., Daentl, D., Brophy, P. J., Lupski, J. R.
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<strong>Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.</strong>
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</p>
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<li>
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<p class="mim-text-font">
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Timmerman, V., De Jonghe, P., Ceuterick, C., De Vriendt, E., Lofgren, A., Nelis, E., Warner, L. E., Lupski, J. R., Martin, J.-J., Van Broeckhoven, C.
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<strong>Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype.</strong>
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</p>
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Unoki, M., Nakamura, Y.
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<strong>Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.</strong>
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Oncogene 20: 4457-4465, 2001.
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<li>
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<p class="mim-text-font">
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Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., Lupski, J. R.
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<strong>Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.</strong>
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Nature Genet. 18: 382-384, 1998.
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[PubMed: 9537424]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Warner, L. E., Mancias, P., Butler, I., Lupski, J. R.
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<strong>Mutation in the early growth response 2 (EGR2) transcription factor associated with recessive congenital hypomyelinating neuropathy (CHN). (Abstract)</strong>
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Warner, L. E., Svaren, J., Milbrandt, J., Lupski, J. R.
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<strong>Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.</strong>
|
|
Hum. Molec. Genet. 8: 1245-1251, 1999.
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[PubMed: 10369870]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Wu, J., Joseph, L., Sukhatme, V. P., Kidd, K. K.
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<strong>A HindIII polymorphism identified by the human early growth response gene 2 (EGR2) on chromosome 10.</strong>
|
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Nucleic Acids Res. 16: 11855 only, 1988.
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[PubMed: 2905450]
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[Full Text: https://doi.org/10.1093/nar/16.24.11855]
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</p>
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</li>
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</ol>
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<div>
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 08/01/2022<br>Paul J. Converse - updated : 8/19/2013<br>Patricia A. Hartz - updated : 12/19/2012<br>George E. Tiller - updated : 7/31/2009<br>Ada Hamosh - updated : 3/10/2009<br>Cassandra L. Kniffin - updated : 11/27/2007<br>Paul J. Converse - updated : 5/5/2006<br>Cassandra L. Kniffin - updated : 11/9/2005<br>Carol A. Bocchini - updated : 12/2/2003<br>Victor A. McKusick - updated : 3/7/2003<br>Dawn Watkins-Chow - updated : 3/18/2002<br>Victor A. McKusick - updated : 8/27/2001<br>George E. Tiller - updated : 1/17/2000<br>Victor A. McKusick - updated : 3/27/1998<br>Victor A. McKusick - updated : 10/24/1997
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</span>
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Victor A. McKusick : 10/12/1988
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carol : 09/10/2024<br>alopez : 08/14/2024<br>alopez : 08/13/2024<br>alopez : 08/01/2022<br>carol : 11/27/2018<br>ckniffin : 11/20/2018<br>alopez : 08/26/2013<br>mgross : 8/19/2013<br>terry : 3/14/2013<br>carol : 12/20/2012<br>carol : 12/20/2012<br>terry : 12/19/2012<br>carol : 10/23/2012<br>terry : 5/29/2012<br>wwang : 8/14/2009<br>terry : 7/31/2009<br>alopez : 3/13/2009<br>terry : 3/10/2009<br>wwang : 12/4/2007<br>ckniffin : 11/27/2007<br>mgross : 5/5/2006<br>wwang : 11/30/2005<br>ckniffin : 11/30/2005<br>wwang : 11/22/2005<br>ckniffin : 11/9/2005<br>terry : 6/2/2004<br>tkritzer : 12/3/2003<br>carol : 12/2/2003<br>ckniffin : 5/15/2003<br>ckniffin : 4/29/2003<br>carol : 4/25/2003<br>ckniffin : 4/23/2003<br>ckniffin : 4/23/2003<br>ckniffin : 4/8/2003<br>terry : 3/7/2003<br>cwells : 2/11/2003<br>cwells : 5/15/2002<br>alopez : 3/18/2002<br>alopez : 3/18/2002<br>mcapotos : 12/19/2001<br>carol : 8/27/2001<br>carol : 9/12/2000<br>terry : 9/11/2000<br>alopez : 9/6/2000<br>alopez : 1/17/2000<br>terry : 12/2/1999<br>carol : 5/20/1999<br>psherman : 6/6/1998<br>alopez : 4/1/1998<br>terry : 4/1/1998<br>terry : 3/27/1998<br>terry : 3/26/1998<br>terry : 10/28/1997<br>alopez : 10/27/1997<br>terry : 10/24/1997<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>carol : 3/24/1989<br>root : 3/13/1989<br>root : 11/4/1988
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