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<title>
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Entry
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- *600037 - ORTHODENTICLE HOMEOBOX 2; OTX2
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- OMIM
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</ul>
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</nav>
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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="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 role="separator" class="divider"></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 class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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<span class="small">
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</form>
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<p />
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<div id="mimAlertBanner">
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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">*600037</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="#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 role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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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 role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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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/600037">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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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000165588;t=ENST00000672264" 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=5015" 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=600037" 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=ENSG00000165588;t=ENST00000672264" 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_001270523,NM_001270524,NM_001270525,NM_021728,NM_172337,NR_073034,NR_073036" 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_021728" 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=600037" 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=07190&isoform_id=07190_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/OTX2" 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/417427,4877580,6815181,10304408,11119420,21618612,27436933,119601098,119601099,189067222,326205242,326205244,326205246,395455071,395455073,395455075,733387123,733387126,828178170,828178172,984697628,984697630" 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/P32243" 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=5015" 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=ENSG00000165588;t=ENST00000672264" 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=OTX2" 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=OTX2" 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+5015" 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/OTX2" 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:5015" 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/5015" 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=chr14&hgg_gene=ENST00000672264.2&hgg_start=56799905&hgg_end=56810479&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:8522" 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://medlineplus.gov/genetics/gene/otx2" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600037[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=600037[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://www.deciphergenomics.org/gene/OTX2/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000165588" 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=OTX2" 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=OTX2" 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=OTX2" 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://lsdb.hgu.mrc.ac.uk/home.php?select_db=OTX2" 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=OTX2&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/PA32849" 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:8522" 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://flybase.org/reports/FBgn0004102.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:97451" 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/OTX2#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:97451" 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/5015/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://omia.org/OMIA002227/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5015" 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="https://wormbase.org/db/gene/gene?name=WBGene00006652;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-980526-406" 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://reactome.org/content/query?q=OTX2&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> 718761007<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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600037
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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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ORTHODENTICLE HOMEOBOX 2; OTX2
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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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ORTHODENTICLE, DROSOPHILA, HOMOLOG OF, 2
|
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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=OTX2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">OTX2</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/14/266?start=-3&limit=10&highlight=266">14q22.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:56799905-56810479&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'})">14:56,799,905-56,810,479</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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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
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14q22.3
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Microphthalmia, syndromic 5
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<a href="/entry/610125"> 610125 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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Pituitary hormone deficiency, combined, 6
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<a href="/entry/613986"> 613986 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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Retinal dystrophy, early-onset, with or without pituitary dysfunction
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<a href="/entry/610125"> 610125 </a>
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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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PheneGene Graphics <span class="caret"></span>
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</button>
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<li><a href="/graph/linear/600037" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/600037" 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-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>Cloning and Expression</strong>
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<p>OTX2 is a homeobox family gene related to a Drosophila gene expressed in the developing head. <a href="#24" class="mim-tip-reference" title="Simeone, A., Acampora, D., Gulisano, M., Stornaiuolo, A., Boncinelli, E. <strong>Nested expression domains of four homeobox genes in developing rostral brain.</strong> Nature 358: 687-690, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1353865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1353865</a>] [<a href="https://doi.org/10.1038/358687a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1353865">Simeone et al. (1992)</a> identified rodent OTX2. Homologs are also found in the chicken, zebrafish, and Xenopus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1353865" 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="Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T. <strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong> J. Clin. Endocr. Metab. 95: 756-764, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>] [<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965921">Dateki et al. (2010)</a> noted that full-length human OTX2 contains 297 amino acids and contains an N-terminal paired type homeodomain, a SIWSPA conserved motif, and 2 tandem tail motifs within a C-terminal transactivation domain. An alternative splice acceptor site at the boundary of intron 3 and exon 4 results in a shorter isoform of 289 amino acids. PCR analysis of human tissues detected the shorter isoform as the major product with strong expression in pituitary gland, thalamus, and hypothalamus, and whole brain. There was not expression of either isoform in spinal cord, kidney, leukocytes, and skin fibroblasts. Western blot analysis detected OTX2 at an apparent molecular mass of 31.6 kD. Subcellular localization analysis showed that OTX2 localized to the nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965921" 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>Gene Structure</strong>
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<p><a href="#8" class="mim-tip-reference" title="Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T. <strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong> J. Clin. Endocr. Metab. 95: 756-764, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>] [<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965921">Dateki et al. (2010)</a> noted that the OTX2 gene contains 5 exons. The first 2 exons are noncoding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965921" 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="#14" class="mim-tip-reference" title="Kastury, K., Druck, T., Huebner, K., Barletta, C., Acampora, D., Simeone, A., Faiella, A., Boncinelli, E. <strong>Chromosome locations of human EMX and OTX genes.</strong> Genomics 22: 41-45, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959790</a>] [<a href="https://doi.org/10.1006/geno.1994.1343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7959790">Kastury et al. (1994)</a> mapped the human OTX2 gene to 14q21-q22 by fluorescence in situ hybridization using a cosmid containing the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7959790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Wyatt, A., Bakrania, P., Bunyan, D. J., Osborne, R. J., Crolla, J. A., Salt, A., Ayuso, C., Newbury-Ecob, R., Abou-Rayyah, Y., Collin, J. R. O., Robinson, D., Ragge, N. <strong>Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma.</strong> Hum. Mutat. 29: E278-E283, 2008. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18781617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18781617</a>] [<a href="https://doi.org/10.1002/humu.20869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18781617">Wyatt et al. (2008)</a> noted that the OTX2 gene maps to chromosome 14q22.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18781617" 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="#3" class="mim-tip-reference" title="Boncinelli, E., Gulisano, M., Broccoli, V. <strong>Emx and Otx homeobox genes in the developing mouse brain.</strong> J. Neurobiol. 24: 1356-1366, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7901323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7901323</a>] [<a href="https://doi.org/10.1002/neu.480241008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7901323">Boncinelli et al. (1993)</a> showed that Otx2 is expressed in the dorsal and most of the ventral regions of the telencephalon, diencephalon, and mesencephalon of developing mouse brain embryos. Its pattern of expression is wider than that of Otx1 (<a href="/entry/600036">600036</a>). Developmentally, Otx2 is expressed first, followed by Otx1, Emx2 (<a href="/entry/600035">600035</a>), and finally by Emx1 (<a href="/entry/600034">600034</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7901323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Florell, S. R., Townsend, J. J., Klatt, E. C., Pysher, T. J., Coffin, C. M., Wittwer, C. T., Viskochil, D. H. <strong>Aprosencephaly and cerebellar dysgenesis in sibs.</strong> Am. J. Med. Genet. 63: 542-548, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826432</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960628)63:4<542::AID-AJMG6>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826432">Florell et al. (1996)</a> described the association of aprosencephaly, absence of optic chiasm, absent mesencephalon, poorly formed metencephalon, and severely dysplastic cerebellum in 2 sibs; see <a href="/entry/601374">601374</a>. Although this complex matched the expression profile of the OTX2 gene, no sequence variations of this gene were identified in the tissues of these fetuses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8826432" 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>Tenascin-C (TNC; <a href="/entry/187380">187380</a>), an extracellular matrix glycoprotein with time- and site-restricted expression during CNS development, has binding sites for neural cells and supports neuronal migration and neurite formation. <a href="#11" class="mim-tip-reference" title="Gherzi, R., Briata, P., Boncinelli, E., Ponassi, M., Querze, G., Viti, F., Corte, G., Zardi, L. <strong>The human homeodomain protein OTX2 binds to the human tenascin-C promoter and trans-represses its activity in transfected cells.</strong> DNA Cell Biol. 16: 559-567, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9174161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9174161</a>] [<a href="https://doi.org/10.1089/dna.1997.16.559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9174161">Gherzi et al. (1997)</a> found that the TNC gene is subject to transcriptional control by OTX2. In cotransfected mammalian cells, OTX2 directly bound with high affinity to a motif in the human TNC promoter and reduced the transcriptional activity of the TNC promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9174161" 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 Gnrh gene (<a href="/entry/152760">152760</a>) is expressed exclusively in a highly restricted population of approximately 800 neurons in the mediobasal hypothalamus in the mouse. The Otx2 homeoprotein colocalizes with Gnrh in embryonic mouse brain. <a href="#15" class="mim-tip-reference" title="Kelley, C. G., Lavorgna, G., Clark, M. E., Boncinelli, E., Mellon, P. L. <strong>The Otx2 homeoprotein regulates expression from the gonadotropin-releasing hormone proximal promoter.</strong> Molec. Endocr. 14: 1246-1256, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10935548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10935548</a>] [<a href="https://doi.org/10.1210/mend.14.8.0509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10935548">Kelley et al. (2000)</a> identified a highly conserved bicoid-related Otx target sequence within the proximal promoter region of the Gnrh gene from several species. This element from the rat Gnrh promoter binds baculovirus-expressed Otx2 protein and Otx2 protein in nuclear extracts of a hypothalamic Gnrh-expressing mouse neuronal cell line, GT1-7. Transient transfection assays indicated that the Gnrh promoter Otx/bicoid site is required for specific expression of the Gnrh gene in GT1-7 cells. Thus, the Gnrh proximal promoter is regulated by the Otx2 homeoprotein. The authors concluded that Otx2 is important in the development of the Gnrh neuron and/or in the maintenance of Gnrh expression in the adult mouse hypothalamus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10935548" 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 a transgenic mouse strain under conditional Otx2 gene ablation, <a href="#19" class="mim-tip-reference" title="Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., Furukawa, T. <strong>Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.</strong> Nature Neurosci. 6: 1255-1263, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14625556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14625556</a>] [<a href="https://doi.org/10.1038/nn1155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14625556">Nishida et al. (2003)</a> found that Otx2 deficiency converted differentiating photoreceptor cells to amacrine-like neurons, reflecting a change in progenitor cell fate, and led to a total lack of pinealocytes in the pineal gland. Expression studies suggested that Otx2 is a direct upstream regulator of another cone-rod homeobox-containing gene, Crx (<a href="/entry/602225">602225</a>), via binding to specific consensus sequences in the Crx promoter. The findings identified Otx2 as a key regulatory gene in photoreceptor cell development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14625556" 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="#17" class="mim-tip-reference" title="Martinez-Morales, J. R., Dolez, V., Rodrigo, I., Zaccarini, R., Leconte, L., Bovolenta, P., Saule, S. <strong>OTX2 activates the molecular network underlying retina pigment epithelium differentiation.</strong> J. Biol. Chem. 278: 21721-21731, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12663655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12663655</a>] [<a href="https://doi.org/10.1074/jbc.M301708200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12663655">Martinez-Morales et al. (2003)</a> showed that mouse Otx2, like Mitf (<a href="/entry/156845">156845</a>), could induce the pigmented phenotype in quail neural retinal cells. Otx2 specifically bound to a bicoid motif present in the promoter regions of genes encoding melanosome glycoproteins, leading to their transactivation, and induction was enhanced by Mitf. Otx2 colocalized with Mitf in the nuclei of retinal pigmented cells, and the 2 proteins interacted in vitro. Because Otx2 and Mitf did not appear to regulate each other's expression, <a href="#17" class="mim-tip-reference" title="Martinez-Morales, J. R., Dolez, V., Rodrigo, I., Zaccarini, R., Leconte, L., Bovolenta, P., Saule, S. <strong>OTX2 activates the molecular network underlying retina pigment epithelium differentiation.</strong> J. Biol. Chem. 278: 21721-21731, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12663655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12663655</a>] [<a href="https://doi.org/10.1074/jbc.M301708200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12663655">Martinez-Morales et al. (2003)</a> proposed that the 2 transcription factors operate at the same hierarchical level to establish the identity of retinal pigment epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12663655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M. <strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong> Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557469</a>] [<a href="https://doi.org/10.1167/iovs.04-0697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15557469">Akagi et al. (2004)</a> reported that CRX and OTX2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells of adult rat. More than 90% of the CRX- and OTX2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells from embryonic rat expressed rod opsin. At least 2 additional key components of the phototransduction cascade, recoverin (<a href="/entry/179618">179618</a>) and G-delta-T1, were expressed by CRX- and OTX2-transfected iris-derived cells. <a href="#1" class="mim-tip-reference" title="Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M. <strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong> Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557469</a>] [<a href="https://doi.org/10.1167/iovs.04-0697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15557469">Akagi et al. (2004)</a> concluded that CRX and OTX2 induced phenotype generation in cells derived from iris or ciliary tissue, which may suggest an approach to photoreceptor cell preparation for retinal transplantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557469" 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="Hever, A. M., Williamson, K. A., van Heyningen, V. <strong>Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2.</strong> Clin. Genet. 69: 459-470, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712695</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00619.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16712695">Hever et al. (2006)</a> reviewed the expression patterns and complex interactions of 3 genes associated with the development of the eye, SOX2 (<a href="/entry/184429">184429</a>), OTX2, and PAX6 (<a href="/entry/607108">607108</a>), noting that these interactions may explain the significant phenotypic overlap between mutations at these 3 loci. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16712695" 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 studies in Xenopus oocytes, <a href="#6" class="mim-tip-reference" title="Danno, H., Michiue, T., Hitachi, K., Yukita, A., Ishiura, S., Asashima, M. <strong>Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.</strong> Proc. Nat. Acad. Sci. 105: 5408-5413, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18385377</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18385377[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0710954105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18385377">Danno et al. (2008)</a> demonstrated specific binding of endogenous OTX2 and SOX2 proteins to a conserved noncoding sequence (CNS1) located approximately 2 kb upstream of the RAX (<a href="/entry/601881">601881</a>) promoter; reporter assays in Xenopus and HEK93T cells revealed that OTX2 and SOX2 synergistically activated RAX transcription via CNS1. GST pull-down and coimmunoprecipitation assays showed that OTX2 and SOX2 physically interacted, and this interaction was affected by missense mutations located in helices 2 and 3 of the SOX2 HMG domain (R74P, <a href="/entry/184429#0008">184429.0008</a>; L97P, <a href="/entry/184429#0004">184429.0004</a>, respectively), resulting in reduced induction of transcription via RAX CNS1. <a href="#6" class="mim-tip-reference" title="Danno, H., Michiue, T., Hitachi, K., Yukita, A., Ishiura, S., Asashima, M. <strong>Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.</strong> Proc. Nat. Acad. Sci. 105: 5408-5413, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18385377</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18385377[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0710954105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18385377">Danno et al. (2008)</a> concluded that direct interaction between OTX2 and SOX2 proteins coordinate RAX expression in eye development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18385377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Panman, L., Papathanou, M., Laguna, A., Oosterveen, T., Volakakis, N., Acampora, D., Kurtsdotter, I., Yoshitake, T., Kehr, J., Joodmardi, E., Muhr, J., Simeone, A., Ericson, J., Perlmann, T. <strong>Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons.</strong> Cell Rep. 8: 1018-1025, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25127144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25127144</a>] [<a href="https://doi.org/10.1016/j.celrep.2014.07.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25127144">Panman et al. (2014)</a> found that Sox6 (<a href="/entry/607257">607257</a>), Otx2, and Nolz1 (ZNF503; <a href="/entry/613902">613902</a>) were selectively expressed in distinct subpopulations of mouse embryonic and adult midbrain dopamine (mDA) neurons that were at the neural progenitor cell stage. Sox6 selectively localized to substantia nigra pars compacta (SNc) mDA neurons, whereas Otx2 and Nolz1 localized to a subset of ventral tegmental area (VTA) mDA neurons. Otx2 restricted Sox6 expression in mDA neuron progenitors and suppressed Sox6 expression in postmitotic SNc mDA neurons. Sox6, on the other hand, suppressed VTA-specific characteristics in mDA neurons, promoted SNc-specific differentiation of mDA neurons, and maintained the characteristics of postmitotic SNc neurons. Immunohistochemical analysis showed that SOX6 expression in human mDA neurons appeared to recapitulate the characteristics seen in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25127144" 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>Early life stress increases risk for depression. <a href="#22" class="mim-tip-reference" title="Pena, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., Goodman, E., Neve, R. L., Shen, L., Nestler, E. J. <strong>Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.</strong> Science 356: 1185-1188, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28619944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28619944</a>] [<a href="https://doi.org/10.1126/science.aan4491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28619944">Pena et al. (2017)</a> established a 2-hit stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA), a brain reward region, to be in a depression-like state. <a href="#22" class="mim-tip-reference" title="Pena, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., Goodman, E., Neve, R. L., Shen, L., Nestler, E. J. <strong>Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.</strong> Science 356: 1185-1188, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28619944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28619944</a>] [<a href="https://doi.org/10.1126/science.aan4491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28619944">Pena et al. (2017)</a> identified a role for the developmental transcription factor Otx2 as an upstream mediator of these enduring effects. Transient juvenile, but not adult, knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. <a href="#22" class="mim-tip-reference" title="Pena, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., Goodman, E., Neve, R. L., Shen, L., Nestler, E. J. <strong>Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.</strong> Science 356: 1185-1188, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28619944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28619944</a>] [<a href="https://doi.org/10.1126/science.aan4491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28619944">Pena et al. (2017)</a> concluded that their work established a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28619944" 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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Using a candidate gene approach, <a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al. (2005)</a> analyzed 333 patients with ocular malformation spectrum defects and identified heterozygous mutations in the OTX2 gene in 11 affected individuals from 8 families (see MCOPS5, <a href="/entry/610125">610125</a>). In 2 families, the mutations occurred de novo in severely affected offspring (<a href="#0001">600037.0001</a> and <a href="#0002">600037.0002</a>, respectively), and in 2 other families, the mutations were inherited from a gonosomal mosaic parent (<a href="#0003">600037.0003</a> and <a href="#0004">600037.0004</a>, respectively). <a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al. (2005)</a> stated that data from these 4 families supported a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. The other 4 families displayed complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15846561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Wyatt, A., Bakrania, P., Bunyan, D. J., Osborne, R. J., Crolla, J. A., Salt, A., Ayuso, C., Newbury-Ecob, R., Abou-Rayyah, Y., Collin, J. R. O., Robinson, D., Ragge, N. <strong>Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma.</strong> Hum. Mutat. 29: E278-E283, 2008. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18781617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18781617</a>] [<a href="https://doi.org/10.1002/humu.20869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18781617">Wyatt et al. (2008)</a> analyzed the OTX2 gene in 165 patients with ocular malformations, primarily clinical anophthalmia, microphthalmia, and/or coloboma, and identified heterozygosity for 2 whole gene deletions, involving OTX2 and several other genes, and 2 nonsense and 2 frameshift mutations, in 8 patients from 6 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18781617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an 8.5-year-old Japanese girl with bilateral clinical anophthalmia, short stature, developmental delay, and partial growth hormone deficiency, who was negative for mutation in the HESX1 (<a href="/entry/601802">601802</a>) and POU1F1 (<a href="/entry/173110">173110</a>) genes, <a href="#7" class="mim-tip-reference" title="Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T. <strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong> J. Clin. Endocr. Metab. 93: 3697-3702, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>] [<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18628516">Dateki et al. (2008)</a> identified a de novo heterozygous frameshift mutation in the OTX2 gene (<a href="#0005">600037.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18628516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 6-year-old Japanese boy with bilateral clinical anophthalmia, short stature, and combined pituitary hormone deficiency, <a href="#25" class="mim-tip-reference" title="Tajima, T., Ohtake, A., Hoshino, M., Amemiya, S., Sasaki, N., Ishizu, K., Fujieda, K. <strong>OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.</strong> J. Clin. Endocr. Metab. 94: 314-319, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18854396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18854396</a>] [<a href="https://doi.org/10.1210/jc.2008-1219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18854396">Tajima et al. (2009)</a> identified a de novo heterozygous frameshift mutation in the OTX2 gene (<a href="#0007">600037.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18854396" 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="Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T. <strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong> J. Clin. Endocr. Metab. 95: 756-764, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>] [<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965921">Dateki et al. (2010)</a> analyzed the OTX2 gene in 16 patients with ocular anomalies, short stature, and pituitary dysfunction, 12 patients with ocular anomalies with or without short stature in whom pituitary function was not investigated, and 66 patients with pituitary dysfunction without ocular anomalies. The patients were negative for mutation in genes known to be associated with their respective phenotypes. <a href="#8" class="mim-tip-reference" title="Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T. <strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong> J. Clin. Endocr. Metab. 95: 756-764, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>] [<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965921">Dateki et al. (2010)</a> identified 3 heterozygous OTX2 truncation mutations in 4 unrelated patients (see, e.g., <a href="#0009">600037.0009</a> and <a href="#0010">600037.0010</a>) and a microdeletion involving the OTX2 gene in 1 patient. The authors concluded that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965921" 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 13.5-year-old boy with unilateral clinical anophthalmia, short stature, and isolated GH deficiency, <a href="#2" class="mim-tip-reference" title="Ashkenazi-Hoffnung, L., Lebenthal, Y., Wyatt, A. W., Ragge, N. K., Dateki, S., Fukami, M., Ogata, T., Phillip, M., Gat-Yablonski, G. <strong>A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency.</strong> Hum. Genet. 127: 721-729, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20396904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20396904</a>] [<a href="https://doi.org/10.1007/s00439-010-0820-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20396904">Ashkenazi-Hoffnung et al. (2010)</a> analyzed the HESX1, SOX2 (<a href="/entry/184429">184429</a>), and OTX2 genes, and identified heterozygosity for a missense mutation in the OTX2 DNA-binding domain (<a href="#0011">600037.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20396904" 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 large 4-generation French family in which 17 individuals had microphthalmia or clinical anophthalmia, <a href="#5" class="mim-tip-reference" title="Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others. <strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong> J. Med. Genet. 49: 373-379, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22577225">Chassaing et al. (2012)</a> identified a heterozygous 1-bp deletion in the OTX2 gene (316delC; <a href="#0012">600037.0012</a>) that segregated with disease. Included in the pedigree were 3 deceased offspring with otocephaly (see <a href="/entry/202650">202650</a>), from whom DNA was unavailable; however, a deceased male infant with an intermediate phenotype was also found to be heterozygous for the 1-bp deletion. Because of the phenotypic variability observed in the French family, <a href="#5" class="mim-tip-reference" title="Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others. <strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong> J. Med. Genet. 49: 373-379, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22577225">Chassaing et al. (2012)</a> screened 5 additional candidate genes known to play a role in vertebrate otocephalic malformations, including PRRX1 (<a href="/entry/167420">167420</a>), but did not detect any likely pathogenic variants. The authors concluded that loss-of-function OTX2 mutations do not sufficiently explain the complex anatomic defects in patients with otocephaly/dysgnathia, suggesting the requirement for a second genetic hit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22577225" 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 mother with unilateral severe microphthalmia and her male fetus with agnathia-otocephaly complex, <a href="#21" class="mim-tip-reference" title="Patat, O., van Ravenswaaij-Arts, C. M. A., Tantau, J., Corsten-Janssen, N., van Tintelen, J. P., Dijkhuizen, T., Kaplan, J., Chassaing, N. <strong>Otocephaly-dysgnathia complex: description of four cases and confirmation of the role of OTX2.</strong> Molec. Syndromol. 4: 302-305, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24167467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24167467</a>] [<a href="https://doi.org/10.1159/000353727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24167467">Patat et al. (2013)</a> identified heterozygosity for a nonsense mutation in the OTX2 gene (R97X; <a href="#0013">600037.0013</a>). The fetus also carried a heterozygous synonymous OTX2 variant (c.525C-G) that was inherited from his asymptomatic father; however, the authors stated that it was unlikely that the silent variant explained the intrafamilial phenotypic variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24167467" 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>Combined Pituitary Hormone Deficiency 6</em></strong></p><p>
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In 19 patients with hypopituitarism (CPHD6; <a href="/entry/613986">613986</a>), <a href="#9" class="mim-tip-reference" title="Diaczok, D., Romero, C., Zunich, J., Marshall, I., Radovick, S. <strong>A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.</strong> J. Clin. Endocr. Metab. 93: 4351-4359, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18728160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18728160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18728160[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/10.1210/jc.2008-1189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18728160">Diaczok et al. (2008)</a> analyzed 8 genes encoding pituitary-specific transcription factors, including HESX1, LHX3 (<a href="/entry/600577">600577</a>), LHX4 (<a href="/entry/602146">602146</a>), OTX2, PITX2 (<a href="/entry/601542">601542</a>), POU1F1, PROP1 (<a href="/entry/601538">601538</a>), and SIX6 (<a href="/entry/606326">606326</a>), and identified heterozygosity for a missense mutation in the OTX2 gene (<a href="#0006">600037.0006</a>) in 2 unrelated patients. One was a 6-year-old boy with deficiency of GH, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), who on MRI had an ectopic neurohypophysis, along with a hypoplastic adenohypophysis and absent or severely hypoplastic pituitary stalk. The other patient was a 14-year-old girl with deficiency of TSH, ACTH, and GH, in whom MRI at age 2 months showed hypoplasia of the pituitary with a posterior bright spot. Neither patient had midline or optic nerve abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18728160" 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>Early-Onset Retinal Dystrophy with or without Pituitary Dysfunction</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Henderson, R. H., Williamson, K. A., Kennedy, J. S., Webster, A. R., Holder, G. E., Robson, A. G., FitzPatrick, D. R., van Heyningen, V., Moore, A. T. <strong>A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.</strong> Molec. Vision 15: 2442-2447, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19956411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19956411</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19956411[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="19956411">Henderson et al. (2009)</a> analyzed DNA samples from 142 patients with Leber congenital amaurosis (LCA; see <a href="/entry/204000">204000</a>) or severe childhood-onset retinal dystrophy (RD; see <a href="/entry/613341">613341</a>) using an 'LCA chip' involving 8 LCA- and RD-associated genes, as well as screening the OTX2 gene. In a 7-year-old boy with early-onset retinal dystrophy, who was negative for all variants assayed by the LCA chip, they identified heterozygosity for a de novo nonsense mutation in the OTX2 gene (<a href="#0008">600037.0008</a>). The patient also had failure to thrive and subsequent short stature (see <a href="/entry/610125">610125</a>), and growth hormone deficiency was suggested indirectly due to low levels of IGF1 (<a href="/entry/147440">147440</a>) and IGFBP3 (<a href="/entry/146732">146732</a>). <a href="#12" class="mim-tip-reference" title="Henderson, R. H., Williamson, K. A., Kennedy, J. S., Webster, A. R., Holder, G. E., Robson, A. G., FitzPatrick, D. R., van Heyningen, V., Moore, A. T. <strong>A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.</strong> Molec. Vision 15: 2442-2447, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19956411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19956411</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19956411[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="19956411">Henderson et al. (2009)</a> stated that the phenotypic spectrum observed in this patient was consistent with the assigned multiple roles of OTX2 in the development and function of both the retinal pigment epithelium (RPE) and neural retina, as well as in the pituitary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19956411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected individuals from 2 Caucasian Canadian families segregating autosomal dominant pattern retinal dystrophy without pituitary dysfunction, <a href="#26" class="mim-tip-reference" title="Vincent, A., Forster, N., Maynes, J. T., Paton, T. A., Billingsley, G., Roslin, N. M., Ali, A., Sutherland, J., Wright, T., Westall, C. A., Paterson, A. D., Marshall, C. R., FORGE Canada Consortium, Heon, E. <strong>OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium.</strong> J. Med. Genet. 51: 797-805, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25293953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25293953</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25293953">Vincent et al. (2014)</a> identified heterozygosity for a missense mutation in the OTX2 gene (E79K; <a href="#0014">600037.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25293953" 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>The mid/hindbrain junction can act as an organizer to direct the development of the midbrain and anterior hindbrain. In mice, Otx2 is expressed in the forebrain and midbrain and Gbx2 (<a href="/entry/601135">601135</a>) is expressed in the anterior hindbrain, with a shared border at the level of the mid/hindbrain organizer. <a href="#18" class="mim-tip-reference" title="Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E., Joyner, A. L. <strong>A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer.</strong> Nature 401: 161-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490024</a>] [<a href="https://doi.org/10.1038/43664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10490024">Millet et al. (1999)</a> demonstrated that in Gbx2 -/- mutants, the earliest phenotype is a posterior expansion of the Otx2 domain during early somite stages. Furthermore, organizer genes are expressed at the shifted Otx2 border, but not in a normal spatial relationship. To test whether Gbx2 is sufficient to position the mid/hindbrain organizer, <a href="#18" class="mim-tip-reference" title="Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E., Joyner, A. L. <strong>A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer.</strong> Nature 401: 161-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490024</a>] [<a href="https://doi.org/10.1038/43664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10490024">Millet et al. (1999)</a> transiently expressed Gbx2 in the caudal Otx2 domain and found that the Otx2 caudal border was indeed shifted rostrally, and a normal-appearing organizer formed at this new Otx2 border. Transgenic embryos then showed an expanded hindbrain and a reduced midbrain at embryonic day 9.5 to 10. <a href="#18" class="mim-tip-reference" title="Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E., Joyner, A. L. <strong>A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer.</strong> Nature 401: 161-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490024</a>] [<a href="https://doi.org/10.1038/43664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10490024">Millet et al. (1999)</a> proposed that the formation of a normal mid/hindbrain organizer depends on a sharp Otx2 caudal border and that Gbx2 is required to position and sharpen this border. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10490024" 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 ectopically expressing Otx2 in the murine presumptive anterior hindbrain using a knockin strategy into the En1 (<a href="/entry/131290">131290</a>) locus, <a href="#4" class="mim-tip-reference" title="Broccoli, V., Boncinelli, E., Wurst, W. <strong>The caudal limit of Otx2 expression positions the isthmic organizer.</strong> Nature 401: 164-168, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490025</a>] [<a href="https://doi.org/10.1038/43670" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10490025">Broccoli et al. (1999)</a> investigated whether the caudal limit of Otx2 expression is instrumental in positioning the isthmic organizer (midbrain/hindbrain junction) and in specifying midbrain versus hindbrain fate. Transgenic offspring displayed a cerebellar ataxia. Morphologic and histologic studies of adult transgenic brains revealed that most of the anterior cerebellar vermis is missing, whereas the inferior colliculus is complementarily enlarged. During early neuronal pattern formation, expression of the midbrain markers Wnt1 (<a href="/entry/164820">164820</a>) and ephrin A5 (<a href="/entry/601535">601535</a>), the isthmic organizer markers Pax2 (<a href="/entry/167409">167409</a>) and Fgf8 (<a href="/entry/600483">600483</a>), and the hindbrain marker Gbx2 are shifted caudally in the presumptive hindbrain territory. <a href="#4" class="mim-tip-reference" title="Broccoli, V., Boncinelli, E., Wurst, W. <strong>The caudal limit of Otx2 expression positions the isthmic organizer.</strong> Nature 401: 164-168, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490025</a>] [<a href="https://doi.org/10.1038/43670" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10490025">Broccoli et al. (1999)</a> concluded that the caudal limit of Otx2 expression is sufficient for positioning the isthmic organizer and encoding caudal midbrain fate within the mid/hindbrain domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10490025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Kimura-Yoshida, C., Nakano, H., Okamura, D., Nakao, K., Yonemura, S., Belo, J. A., Aizawa, S., Matsui, Y., Matsuo, I. <strong>Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm.</strong> Dev. Cell 9: 639-650, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16256739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16256739</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.09.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16256739">Kimura-Yoshida et al. (2005)</a> found that Otx2 deficiency resulted in defective conversion of the mouse embryonic axis from the proximal-distal orientation to a prospective anterior-posterior polarity. Defective axis conversion was rescued by expression of Dkk1 (<a href="/entry/605189">605189</a>), a Wnt (see WNT1; <a href="/entry/164820">164820</a>) antagonist, or following removal of 1 copy of the beta-catenin gene (see CTNNB1; <a href="/entry/116806">116806</a>). Furthermore, the asymmetric distribution of beta-catenin localization was impaired in Otx2-deficient embryos. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16256739" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others. <strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong> J. Med. Genet. 49: 373-379, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22577225">Chassaing et al. (2012)</a> transiently suppressed the zebrafish ortholog of OTX2. At 5 days postfertilization, the zebrafish showed mild microphthalmia and shortening of the pharyngeal skeleton that increased in penetrance in a dose-dependent manner. Combined suppression of otx2 and other otocephaly-associated genes, including prrx1 (<a href="/entry/167420">167420</a>), pgap1 (<a href="/entry/611655">611655</a>), and msx1 (<a href="/entry/142983">142983</a>), demonstrated a synergistic exacerbation of the phenotypes: pairwise suppression resulted in increased mortality and a new class of embryos that displayed severe microphthalmia, eye fusion along the midline, and severe disorganization of mandibular cartilage. <a href="#5" class="mim-tip-reference" title="Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others. <strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong> J. Med. Genet. 49: 373-379, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22577225">Chassaing et al. (2012)</a> concluded that suppression of otx2, in combination with loss of function of other loci contributing to otocephaly phenotypes, can modulate phenotypic severity in the manifestation of craniofacial malformations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22577225" 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 mouse, <a href="#28" class="mim-tip-reference" title="Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A., Chambers, I. <strong>OTX2 restricts entry to the mouse germline.</strong> Nature 562: 595-599, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30283136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30283136</a>] [<a href="https://doi.org/10.1038/s41586-018-0581-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30283136">Zhang et al. (2018)</a> showed that downregulation of Otx2 precedes the initiation of the primordial germ cell (PGC) program both in vitro and in vivo. Deletion of Otx2 in vitro markedly increased the efficiency of PGC-like cell differentiation and prolonged the period of PGC competence. In the absence of Otx2 activity, differentiation of PGC-like cells became independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC transcription factor Blimp1 (<a href="/entry/603423">603423</a>). Deletion of Otx2 in vivo increased primordial germ cell numbers. <a href="#28" class="mim-tip-reference" title="Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A., Chambers, I. <strong>OTX2 restricts entry to the mouse germline.</strong> Nature 562: 595-599, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30283136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30283136</a>] [<a href="https://doi.org/10.1038/s41586-018-0581-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30283136">Zhang et al. (2018)</a> concluded that OTX2 functions repressively upstream of PGC transcription factors, acting as a roadblock to limit entry of epiblast cells to the germline to a small window in space and time, thereby ensuring correct numerical segregation of germline cells from the soma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30283136" 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 href="https://www.ncbi.nlm.nih.gov/clinvar?term=600037[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786205873 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205873;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=rs786205873" 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=rs786205873" 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 boy with right clinical anophthalmia and left microphthalmia and associated features (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al. (2005)</a> identified heterozygosity for a de novo 2-bp insertion (464GC) in exon 5 of the OTX2 gene, predicted to result in a nonsense codon 22 amino acids downstream. Based on numbering from the first residue of the initiation codon as +1, the 635insGC mutation is renumbered as 464insGC, and exon numbering includes the first 2 noncoding exons (<a href="#7" class="mim-tip-reference" title="Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T. <strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong> J. Clin. Endocr. Metab. 93: 3697-3702, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>] [<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18628516">Dateki et al., 2008</a>). The patient also had left-sided persistent pupillary membrane, iris coloboma, high hypermetropia, and chorioretinal coloboma. MRI scan at age 1 month showed partial agenesis of the corpus callosum with a normal-sized pituitary gland, absent right optic nerve and small left optic nerve, thin chiasm, and malformation of the hippocampi bilaterally. Examination at age 4 years revealed marked developmental delay, generalized hypotonia, increased joint laxity, and microcephaly. Neither the parents nor the unaffected brother carried the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15846561+18628516" 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>In a boy with asymmetric microphthalmia and associated features (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al. (2005)</a> identified heterozygosity for a de novo 265C-G transversion in exon 5 of the OTX2 gene, resulting in an arg89-to-gly (R89G) substitution in the homeodomain. On an MRI at age 3 weeks, there was bilateral optic nerve aplasia, the chiasm was not visualized, and there was thinning of the corpus callosum anteriorly; when repeated at 2 years of age, no optic chiasm was seen but the corpus callosum appeared normal. Horizontal corneal diameters were 6.5 mm and 8.0 mm on the right and left, respectively. The only systemic abnormalities at birth were midline dermoid cysts on the forehead and nasal bridge. Cognitive and language skills were normal at age 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15846561" 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>Based on numbering from the initiation codon, 346C-G is renumbered as 265C-G, and exon numbering includes the first 2 noncoding exons (<a href="#7" class="mim-tip-reference" title="Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T. <strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong> J. Clin. Endocr. Metab. 93: 3697-3702, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>] [<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18628516">Dateki et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18628516" 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">rs786205874 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205874;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=rs786205874" 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=rs786205874" 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=RCV000010125" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010125" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010125</a>
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<p>In a female infant with bilateral severe microphthalmia and associated features (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al. (2005)</a> identified heterozygosity for a 1-bp deletion (81delC) in exon 3 of the OTX2 gene, predicted to result in a termination codon in exon 4. CT scan revealed a thickened septum pellucidum and slightly enlarged lateral ventricles. A fetus, terminated after ultrasound revealed bilateral microphthalmia and agenesis of the corpus callosum, also carried the mutation. The phenotypically normal mother was found to be a gonosomal mosaic carrier of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15846561" 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>Based on numbering from the first residue of initiation codon as +1, the 252delC mutation is renumbered as 81delC, and exon numbering includes the first 2 noncoding exons (<a href="#7" class="mim-tip-reference" title="Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T. <strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong> J. Clin. Endocr. Metab. 93: 3697-3702, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>] [<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18628516">Dateki et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18628516" 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"><span class="text-primary">●</span> rs104894465 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894465;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894465?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894465" 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=rs104894465" 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=RCV000010126" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010126" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010126</a>
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<p>In a sister and brother with bilateral microphthalmia and associated features (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al. (2005)</a> identified heterozygosity for a 537T-A transversion in exon 5 of the OTX2 gene, resulting in a tyr179-to-ter (Y179X) substitution in the C-terminal domain. The sister also had bilateral colobomas and microcornea, left-sided cataract, bilateral fifth finger clinodactyly, severe learning difficulties, and a seizure disorder. The brother, who had borderline microphthalmic eyes, was given a diagnosis of Leber congenital amaurosis (LCA; see <a href="/entry/204000">204000</a>) at birth; examination at age 26 years revealed pale optic discs, thin retinal vessels, atrophic maculae, and large clumps of pigment in the midperiphery, consistent with the diagnosis of LCA. ERG was absent, and he had nystagmus, bilateral peripheral anterior synechiae, and a right-sided hearing loss. The mother was found to be a gonosomal mosaic carrier of the mutation; examination of her eyes revealed retinal dystrophy comparable to that seen in her son, night blindness, and extensive peripheral field loss bilaterally. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15846561" 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>Based on numbering from the initiation codon as +1, 708T-A is renumbered as 537T-A, and exon numbering includes the first 2 noncoding exons (<a href="#7" class="mim-tip-reference" title="Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T. <strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong> J. Clin. Endocr. Metab. 93: 3697-3702, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>] [<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18628516">Dateki et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18628516" 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">rs1555350223 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555350223;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=rs1555350223" 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=rs1555350223" 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=RCV000594111 OR RCV000596696 OR RCV003530088" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000594111, RCV000596696, RCV003530088" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000594111...</a>
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<p>In an 8.5-year-old Japanese girl with bilateral clinical anophthalmia, short stature, developmental delay, and partial growth hormone deficiency (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#7" class="mim-tip-reference" title="Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T. <strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong> J. Clin. Endocr. Metab. 93: 3697-3702, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>] [<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18628516">Dateki et al. (2008)</a> identified heterozygosity for a de novo 1-bp insertion (402insC) in exon 5 of the OTX2 gene, predicted to cause a frameshift and premature termination codon resulting in retention of the homeodomain but loss of the transactivation domain as well as the SIWSPA motif. The mutation was not found in either parent. Functional studies showed that both wildtype and mutant protein localized to the nucleus; however, wildtype OTX2 markedly transactivated the reporters for the IRBP (<a href="/entry/180290">180290</a>), HESX1 (<a href="/entry/601802">601802</a>), and POU1F1 (<a href="/entry/173110">173110</a>) genes, whereas mutant OTX2 barely retained transactivation activities and had no dominant-negative effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18628516" 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>.0006 PITUITARY HORMONE DEFICIENCY, COMBINED, 6</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"><span class="text-primary">●</span> rs370761964 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs370761964;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs370761964?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs370761964" 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=rs370761964" 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=RCV000022923" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022923" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022923</a>
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<p>In 2 unrelated patients with multiple pituitary hormone deficiencies (CPHD6; <a href="/entry/613986">613986</a>), <a href="#9" class="mim-tip-reference" title="Diaczok, D., Romero, C., Zunich, J., Marshall, I., Radovick, S. <strong>A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.</strong> J. Clin. Endocr. Metab. 93: 4351-4359, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18728160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18728160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18728160[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/10.1210/jc.2008-1189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18728160">Diaczok et al. (2008)</a> identified heterozygosity for a 698A-G transition in exon 5 of the OTX2 gene, resulting in an asn233-to-ser (N233S) substitution in the transcription factor region. Electrophoretic mobility shift assay (EMSA) with murine Otx2 demonstrated that both wildtype and mutant Otx2 bound equally well to 2 specific sites in the 5-prime flanking region of the HESX1 gene (<a href="/entry/601802">601802</a>). Functional studies in 293T cells showed that the mutant Otx2 had a dominant negative effect on the proximal promoter region of HESX1 and a multiple bicoid binding site reporter construct, and studies in the GH-producing GH3 cells showed that N233S Otx2 repressed reporter expression. <a href="#9" class="mim-tip-reference" title="Diaczok, D., Romero, C., Zunich, J., Marshall, I., Radovick, S. <strong>A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.</strong> J. Clin. Endocr. Metab. 93: 4351-4359, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18728160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18728160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18728160[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/10.1210/jc.2008-1189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18728160">Diaczok et al. (2008)</a> concluded that the heterozygous N233S OTX2 mutation acts as a dominant inhibitor of the HESX1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18728160" 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>.0007 MICROPHTHALMIA, SYNDROMIC 5</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">rs1566623121 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566623121;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=rs1566623121" 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=rs1566623121" 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=RCV000022924" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022924" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022924</a>
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<p>In a 6-year-old boy with bilateral clinical anophthalmia, short stature, and combined pituitary hormone deficiency (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#25" class="mim-tip-reference" title="Tajima, T., Ohtake, A., Hoshino, M., Amemiya, S., Sasaki, N., Ishizu, K., Fujieda, K. <strong>OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.</strong> J. Clin. Endocr. Metab. 94: 314-319, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18854396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18854396</a>] [<a href="https://doi.org/10.1210/jc.2008-1219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18854396">Tajima et al. (2009)</a> identified a de novo heterozygous 2-bp insertion (576insCT) in exon 5 of the OTX2 gene, causing a frameshift and premature termination codon, resulting in a protein lacking the C-terminal region. The mutation was not found in the unaffected parents or in 50 Japanese controls. Functional analysis in mice revealed that the mutant protein localized to the nucleus, but activation of the promoters of the HESX1 (<a href="/entry/601802">601802</a>) and POU1F1 (<a href="/entry/173110">173110</a>) genes was absent or less than 50% of wildtype, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18854396" 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>.0008 RETINAL DYSTROPHY, EARLY-ONSET, WITH PITUITARY DYSFUNCTION</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">rs786205879 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205879;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=rs786205879" 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=rs786205879" 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=RCV000022925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022925</a>
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<p>In a 7-year-old boy with severe childhood-onset retinal dystrophy and growth hormone deficiency (see <a href="/entry/610125">610125</a>), <a href="#12" class="mim-tip-reference" title="Henderson, R. H., Williamson, K. A., Kennedy, J. S., Webster, A. R., Holder, G. E., Robson, A. G., FitzPatrick, D. R., van Heyningen, V., Moore, A. T. <strong>A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.</strong> Molec. Vision 15: 2442-2447, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19956411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19956411</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19956411[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="19956411">Henderson et al. (2009)</a> identified heterozygosity for a de novo 413C-G transversion in the OTX2 gene, resulting in a ser138-to-ter (S138X) substitution. The patient, who was noted to have poor vision and nyctalopia during his first year of life, also had failure to thrive and growth hormone deficiency. The mutation was not found in his unaffected parents or in 181 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19956411" 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>.0009 MICROPHTHALMIA, SYNDROMIC 5</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">rs1566624472 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566624472;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=rs1566624472" 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=rs1566624472" 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 3-year-old boy with right clinical anophthalmia and left microphthalmia, who had developmental delay, short stature, and growth hormone deficiency (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#8" class="mim-tip-reference" title="Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T. <strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong> J. Clin. Endocr. Metab. 95: 756-764, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>] [<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965921">Dateki et al. (2010)</a> identified heterozygosity for a de novo 16-bp deletion (221_236del) in exon 4 of the OTX2 gene, predicted to cause a frameshift and premature termination codon. The deletion was not found in the unaffected parents or in 100 controls. Functional analysis revealed that the mutant protein had no transactivation functions for 4 promoters that were transactivated by wildtype OTX2; no dominant-negative effect was observed. Brain MRI revealed pituitary hypoplasia and ectopic posterior pituitary. The patient also had right-sided retractile testis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965921" 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>.0010 MICROPHTHALMIA, SYNDROMIC 5</strong>
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OTX2, GLY188TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514463 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514463;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=rs397514463" 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=rs397514463" 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=RCV000022927 OR RCV001857357" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022927, RCV001857357" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022927...</a>
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<p>In a 15-year-old boy and an unrelated 10-year-old boy, both of whom had bilateral microphthalmia and developmental delay (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#8" class="mim-tip-reference" title="Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T. <strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong> J. Clin. Endocr. Metab. 95: 756-764, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>] [<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965921">Dateki et al. (2010)</a> identified heterozygosity for a 562G-T transversion in exon 5 of the OTX2 gene, predicted to cause a gly188-to-ter (G188X) substitution. The mutation was not found in 100 controls; the parents refused molecular studies. Functional analysis revealed that the mutant protein had reduced transactivation function (approximately 50% of wildtype) for the 4 promoters tested, with no dominant-negative effect. The 15-year-old patient had deficiency of the pituitary hormones GH, TSH, PRL, LH, and FSH, and brain MRI revealed pituitary hypoplasia and ectopic posterior pituitary. The 10-year-old patient, who also had seizures, had 'no discernible pituitary dysfunction' and did not undergo brain MRI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965921" 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">rs1566623392 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566623392;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=rs1566623392" 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=rs1566623392" 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=RCV000022928" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022928" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022928</a>
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<p>In a 13.5-year-old boy of Sephardic Jewish descent who had unilateral clinical anophthalmia, short stature, and isolated GH deficiency (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#2" class="mim-tip-reference" title="Ashkenazi-Hoffnung, L., Lebenthal, Y., Wyatt, A. W., Ragge, N. K., Dateki, S., Fukami, M., Ogata, T., Phillip, M., Gat-Yablonski, G. <strong>A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency.</strong> Hum. Genet. 127: 721-729, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20396904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20396904</a>] [<a href="https://doi.org/10.1007/s00439-010-0820-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20396904">Ashkenazi-Hoffnung et al. (2010)</a> identified heterozygosity for a 270A-T transversion in exon 3 of the OTX2 gene, resulting in an arg90-to-ser (R90S) substitution in the DNA-binding homeodomain. His father, who had short stature but normal eye structure and unknown endocrine status, was also heterozygous for the mutation. The mutation was not present in the unaffected mother or an unaffected brother, and had not previously been found in 261 controls (<a href="#23" class="mim-tip-reference" title="Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others. <strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong> Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15846561">Ragge et al., 2005</a>; <a href="#27" class="mim-tip-reference" title="Wyatt, A., Bakrania, P., Bunyan, D. J., Osborne, R. J., Crolla, J. A., Salt, A., Ayuso, C., Newbury-Ecob, R., Abou-Rayyah, Y., Collin, J. R. O., Robinson, D., Ragge, N. <strong>Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma.</strong> Hum. Mutat. 29: E278-E283, 2008. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18781617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18781617</a>] [<a href="https://doi.org/10.1002/humu.20869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18781617">Wyatt et al., 2008</a>). Functional analysis revealed that the R90S mutation did not affect the expression or nuclear localization of the protein, but inhibited its DNA-binding activity as well as its transactivation capability, thus rendering it nonfunctional. No dominant-negative effect was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20396904+15846561+18781617" 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>.0012 MICROPHTHALMIA, SYNDROMIC 5</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">rs786205884 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205884;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=rs786205884" 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=rs786205884" 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=RCV000170470" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170470" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170470</a>
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<p>In affected members of a large 4-generation French family in which 17 individuals had microphthalmia or clinical anophthalmia, 3 of whom also exhibited moderate to severe mental retardation (MCOPS5; <a href="/entry/610125">610125</a>), <a href="#5" class="mim-tip-reference" title="Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others. <strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong> J. Med. Genet. 49: 373-379, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22577225">Chassaing et al. (2012)</a> identified a heterozygous 1-bp deletion (c.316delC, NM_021728.2) in the OTX2 gene, causing a frameshift predicted to result in premature termination (Gln106AsnfsTer11) within the glutamine stretch. Included in the pedigree were 3 deceased offspring with otocephaly, from whom DNA was unavailable; however, 2 were sibs born of an affected mother who carried the deletion, and another deceased male infant who exhibited clinical features overlapping both microphthalmia and otocephaly was also found to be heterozygous for the 1-bp deletion. <a href="#5" class="mim-tip-reference" title="Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others. <strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong> J. Med. Genet. 49: 373-379, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22577225">Chassaing et al. (2012)</a> stated that loss-of-function OTX2 mutations do not sufficiently explain the complex anatomic defects in patients with otocephaly/dysgnathia, suggesting the requirement for a second genetic hit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22577225" 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>.0013 MICROPHTHALMIA, SYNDROMIC 5</strong>
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OTX2, ARG97TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894464 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894464;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=rs104894464" 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=rs104894464" 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=RCV000170471 OR RCV001558575" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170471, RCV001558575" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170471...</a>
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<p>In a mother with unilateral severe microphthalmia and her male fetus with agnathia-otocephaly complex (see MCOPS5, <a href="/entry/610125">610125</a>), <a href="#21" class="mim-tip-reference" title="Patat, O., van Ravenswaaij-Arts, C. M. A., Tantau, J., Corsten-Janssen, N., van Tintelen, J. P., Dijkhuizen, T., Kaplan, J., Chassaing, N. <strong>Otocephaly-dysgnathia complex: description of four cases and confirmation of the role of OTX2.</strong> Molec. Syndromol. 4: 302-305, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24167467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24167467</a>] [<a href="https://doi.org/10.1159/000353727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24167467">Patat et al. (2013)</a> identified heterozygosity for a c.289C-T transition (c.289C-T, NM_021728.2) in the OTX2 gene, resulting in an arg97-to-ter (R97X) substitution. The fetus also carried a heterozygous synonymous OTX2 variant (c.525C-G) that was inherited from his asymptomatic father; however, the authors stated that it was unlikely that the silent variant explained the intrafamilial phenotypic variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24167467" 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>.0014 RETINAL DYSTROPHY, EARLY-ONSET, WITHOUT PITUITARY DYSFUNCTION</strong>
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OTX2, GLU79LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786205224 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205224;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=rs786205224" 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=rs786205224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000170472 OR RCV000494571" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170472, RCV000494571" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170472...</a>
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<p>In affected individuals from 2 Caucasian Canadian families segregating autosomal dominant pattern retinal dystrophy without pituitary dysfunction (see <a href="/entry/610125">610125</a>), <a href="#26" class="mim-tip-reference" title="Vincent, A., Forster, N., Maynes, J. T., Paton, T. A., Billingsley, G., Roslin, N. M., Ali, A., Sutherland, J., Wright, T., Westall, C. A., Paterson, A. D., Marshall, C. R., FORGE Canada Consortium, Heon, E. <strong>OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium.</strong> J. Med. Genet. 51: 797-805, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25293953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25293953</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25293953">Vincent et al. (2014)</a> identified heterozygosity for a c.235G-A transition (c.235G-A, NM_001270523.1) in exon 4 of the OTX2 gene, resulting in a glu79-to-lys (E79K) substitution at a highly conserved residue in the homeobox domain. Haplotype analysis revealed a 19.68-cM shared haplotype between SNPs <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs17107459;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs17107459</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs710050;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs710050</a>; the number of generations between a common ancestor and affected individuals in the youngest generation in each family was estimated to be 5, making them fourth cousins. Of the 7 patients who underwent ocular examination, 3 exhibited a butterfly pattern of retinal dystrophy, 2 showed a grouped pigmentation pattern, 1 showed an annular pattern, and 1 showed only a dull foveal reflex with no apparent pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25293953" 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="Akagi2004" class="mim-anchor"></a>
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Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M.
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<strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong>
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Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557469" 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/10.1167/iovs.04-0697" target="_blank">Full Text</a>]
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Ashkenazi-Hoffnung, L., Lebenthal, Y., Wyatt, A. W., Ragge, N. K., Dateki, S., Fukami, M., Ogata, T., Phillip, M., Gat-Yablonski, G.
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<strong>A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency.</strong>
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Hum. Genet. 127: 721-729, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20396904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20396904</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20396904" 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/s00439-010-0820-9" target="_blank">Full Text</a>]
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Boncinelli, E., Gulisano, M., Broccoli, V.
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<strong>Emx and Otx homeobox genes in the developing mouse brain.</strong>
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J. Neurobiol. 24: 1356-1366, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7901323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7901323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7901323" 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/10.1002/neu.480241008" target="_blank">Full Text</a>]
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Broccoli, V., Boncinelli, E., Wurst, W.
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<strong>The caudal limit of Otx2 expression positions the isthmic organizer.</strong>
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Nature 401: 164-168, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10490025" 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/10.1038/43670" target="_blank">Full Text</a>]
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Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others.
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<strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong>
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J. Med. Genet. 49: 373-379, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22577225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22577225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22577225" 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/10.1136/jmedgenet-2012-100892" target="_blank">Full Text</a>]
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Danno, H., Michiue, T., Hitachi, K., Yukita, A., Ishiura, S., Asashima, M.
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<strong>Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.</strong>
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Proc. Nat. Acad. Sci. 105: 5408-5413, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18385377</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18385377[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=18385377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0710954105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Dateki2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T.
|
|
<strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong>
|
|
J. Clin. Endocr. Metab. 93: 3697-3702, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18628516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18628516</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18628516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2008-0720" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Dateki2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T.
|
|
<strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong>
|
|
J. Clin. Endocr. Metab. 95: 756-764, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2009-1334" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Diaczok2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Diaczok, D., Romero, C., Zunich, J., Marshall, I., Radovick, S.
|
|
<strong>A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 93: 4351-4359, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18728160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18728160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18728160[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=18728160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2008-1189" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Florell1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Florell, S. R., Townsend, J. J., Klatt, E. C., Pysher, T. J., Coffin, C. M., Wittwer, C. T., Viskochil, D. H.
|
|
<strong>Aprosencephaly and cerebellar dysgenesis in sibs.</strong>
|
|
Am. J. Med. Genet. 63: 542-548, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826432</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8826432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960628)63:4<542::AID-AJMG6>3.0.CO;2-Q" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Gherzi1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gherzi, R., Briata, P., Boncinelli, E., Ponassi, M., Querze, G., Viti, F., Corte, G., Zardi, L.
|
|
<strong>The human homeodomain protein OTX2 binds to the human tenascin-C promoter and trans-represses its activity in transfected cells.</strong>
|
|
DNA Cell Biol. 16: 559-567, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9174161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9174161</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9174161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1089/dna.1997.16.559" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Henderson2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Henderson, R. H., Williamson, K. A., Kennedy, J. S., Webster, A. R., Holder, G. E., Robson, A. G., FitzPatrick, D. R., van Heyningen, V., Moore, A. T.
|
|
<strong>A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.</strong>
|
|
Molec. Vision 15: 2442-2447, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19956411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19956411</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19956411[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=19956411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hever2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hever, A. M., Williamson, K. A., van Heyningen, V.
|
|
<strong>Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2.</strong>
|
|
Clin. Genet. 69: 459-470, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16712695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2006.00619.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Kastury1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kastury, K., Druck, T., Huebner, K., Barletta, C., Acampora, D., Simeone, A., Faiella, A., Boncinelli, E.
|
|
<strong>Chromosome locations of human EMX and OTX genes.</strong>
|
|
Genomics 22: 41-45, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959790</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7959790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1343" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Kelley2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kelley, C. G., Lavorgna, G., Clark, M. E., Boncinelli, E., Mellon, P. L.
|
|
<strong>The Otx2 homeoprotein regulates expression from the gonadotropin-releasing hormone proximal promoter.</strong>
|
|
Molec. Endocr. 14: 1246-1256, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10935548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10935548</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10935548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/mend.14.8.0509" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Kimura-Yoshida2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kimura-Yoshida, C., Nakano, H., Okamura, D., Nakao, K., Yonemura, S., Belo, J. A., Aizawa, S., Matsui, Y., Matsuo, I.
|
|
<strong>Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm.</strong>
|
|
Dev. Cell 9: 639-650, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16256739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16256739</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16256739" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.devcel.2005.09.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Martinez-Morales2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martinez-Morales, J. R., Dolez, V., Rodrigo, I., Zaccarini, R., Leconte, L., Bovolenta, P., Saule, S.
|
|
<strong>OTX2 activates the molecular network underlying retina pigment epithelium differentiation.</strong>
|
|
J. Biol. Chem. 278: 21721-21731, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12663655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12663655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12663655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M301708200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Millet1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E., Joyner, A. L.
|
|
<strong>A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer.</strong>
|
|
Nature 401: 161-164, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10490024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10490024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10490024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/43664" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Nishida2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., Furukawa, T.
|
|
<strong>Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.</strong>
|
|
Nature Neurosci. 6: 1255-1263, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14625556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14625556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14625556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nn1155" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Panman2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Panman, L., Papathanou, M., Laguna, A., Oosterveen, T., Volakakis, N., Acampora, D., Kurtsdotter, I., Yoshitake, T., Kehr, J., Joodmardi, E., Muhr, J., Simeone, A., Ericson, J., Perlmann, T.
|
|
<strong>Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons.</strong>
|
|
Cell Rep. 8: 1018-1025, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25127144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25127144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25127144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.celrep.2014.07.016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Patat2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Patat, O., van Ravenswaaij-Arts, C. M. A., Tantau, J., Corsten-Janssen, N., van Tintelen, J. P., Dijkhuizen, T., Kaplan, J., Chassaing, N.
|
|
<strong>Otocephaly-dysgnathia complex: description of four cases and confirmation of the role of OTX2.</strong>
|
|
Molec. Syndromol. 4: 302-305, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24167467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24167467</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24167467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000353727" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Pena2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pena, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., Goodman, E., Neve, R. L., Shen, L., Nestler, E. J.
|
|
<strong>Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.</strong>
|
|
Science 356: 1185-1188, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28619944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28619944</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28619944" 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.aan4491" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Ragge2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others.
|
|
<strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong>
|
|
Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15846561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15846561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15846561[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=15846561" 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/10.1086/430721" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="24" class="mim-anchor"></a>
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<a id="Simeone1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Simeone, A., Acampora, D., Gulisano, M., Stornaiuolo, A., Boncinelli, E.
|
|
<strong>Nested expression domains of four homeobox genes in developing rostral brain.</strong>
|
|
Nature 358: 687-690, 1992.
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|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1353865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1353865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1353865" 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/10.1038/358687a0" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="25" class="mim-anchor"></a>
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<a id="Tajima2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tajima, T., Ohtake, A., Hoshino, M., Amemiya, S., Sasaki, N., Ishizu, K., Fujieda, K.
|
|
<strong>OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.</strong>
|
|
J. Clin. Endocr. Metab. 94: 314-319, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18854396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18854396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18854396" 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/10.1210/jc.2008-1219" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="26" class="mim-anchor"></a>
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<a id="Vincent2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vincent, A., Forster, N., Maynes, J. T., Paton, T. A., Billingsley, G., Roslin, N. M., Ali, A., Sutherland, J., Wright, T., Westall, C. A., Paterson, A. D., Marshall, C. R., FORGE Canada Consortium, Heon, E.
|
|
<strong>OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium.</strong>
|
|
J. Med. Genet. 51: 797-805, 2014.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25293953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25293953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25293953" 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/10.1136/jmedgenet-2014-102620" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="27" class="mim-anchor"></a>
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<a id="Wyatt2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wyatt, A., Bakrania, P., Bunyan, D. J., Osborne, R. J., Crolla, J. A., Salt, A., Ayuso, C., Newbury-Ecob, R., Abou-Rayyah, Y., Collin, J. R. O., Robinson, D., Ragge, N.
|
|
<strong>Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma.</strong>
|
|
Hum. Mutat. 29: E278-E283, 2008. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18781617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18781617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18781617" 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/10.1002/humu.20869" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="28" class="mim-anchor"></a>
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<a id="Zhang2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A., Chambers, I.
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<strong>OTX2 restricts entry to the mouse germline.</strong>
|
|
Nature 562: 595-599, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30283136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30283136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30283136" 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/s41586-018-0581-5" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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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 : 02/04/2020
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</span>
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</div>
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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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Ada Hamosh - updated : 02/26/2019<br>Ada Hamosh - updated : 01/31/2018<br>Marla J. F. O'Neill - updated : 5/6/2015<br>Marla J. F. O'Neill - updated : 4/27/2011<br>Marla J. F. O'Neill - updated : 6/6/2008<br>Marla J. F. O'Neill - updated : 7/27/2006<br>Marla J. F. O'Neill - updated : 5/16/2006<br>Patricia A. Hartz - updated : 12/21/2005<br>Jane Kelly - updated : 3/3/2005<br>Cassandra L. Kniffin - updated : 3/2/2004<br>John A. Phillips, III - updated : 7/12/2002<br>Ada Hamosh - updated : 2/18/2000<br>Iosif W. Lurie - updated : 8/11/1996<br>Alan F. Scott - updated : 1/29/1996
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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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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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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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Victor A. McKusick : 7/14/1994
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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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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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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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mgross : 02/04/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/25/2019<br>alopez : 02/26/2019<br>alopez : 01/31/2018<br>carol : 04/21/2016<br>carol : 2/25/2016<br>carol : 5/22/2015<br>carol : 5/7/2015<br>carol : 5/7/2015<br>mcolton : 5/6/2015<br>alopez : 4/3/2015<br>wwang : 5/20/2011<br>wwang : 5/20/2011<br>terry : 4/27/2011<br>terry : 11/3/2010<br>wwang : 6/9/2008<br>terry : 6/6/2008<br>wwang : 10/12/2006<br>wwang : 8/1/2006<br>terry : 7/27/2006<br>carol : 6/2/2006<br>carol : 5/17/2006<br>terry : 5/16/2006<br>wwang : 1/24/2006<br>wwang : 12/21/2005<br>tkritzer : 3/3/2005<br>terry : 3/18/2004<br>tkritzer : 3/5/2004<br>ckniffin : 3/2/2004<br>alopez : 7/12/2002<br>alopez : 2/18/2000<br>alopez : 7/10/1997<br>carol : 8/11/1996<br>terry : 4/17/1996<br>mark : 1/29/1996<br>jason : 7/15/1994<br>randerso : 7/14/1994
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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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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 600037
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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ORTHODENTICLE HOMEOBOX 2; OTX2
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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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<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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ORTHODENTICLE, DROSOPHILA, HOMOLOG OF, 2
|
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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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<p>
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: OTX2</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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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 718761007;
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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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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 14q22.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 14:56,799,905-56,810,479 </span>
|
|
</em>
|
|
</strong>
|
|
<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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<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-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
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<tr>
|
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<td rowspan="3">
|
|
<span class="mim-font">
|
|
14q22.3
|
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</span>
|
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</td>
|
|
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<td>
|
|
<span class="mim-font">
|
|
Microphthalmia, syndromic 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610125
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Pituitary hormone deficiency, combined, 6
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613986
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Retinal dystrophy, early-onset, with or without pituitary dysfunction
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610125
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
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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>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<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>OTX2 is a homeobox family gene related to a Drosophila gene expressed in the developing head. Simeone et al. (1992) identified rodent OTX2. Homologs are also found in the chicken, zebrafish, and Xenopus. </p><p>Dateki et al. (2010) noted that full-length human OTX2 contains 297 amino acids and contains an N-terminal paired type homeodomain, a SIWSPA conserved motif, and 2 tandem tail motifs within a C-terminal transactivation domain. An alternative splice acceptor site at the boundary of intron 3 and exon 4 results in a shorter isoform of 289 amino acids. PCR analysis of human tissues detected the shorter isoform as the major product with strong expression in pituitary gland, thalamus, and hypothalamus, and whole brain. There was not expression of either isoform in spinal cord, kidney, leukocytes, and skin fibroblasts. Western blot analysis detected OTX2 at an apparent molecular mass of 31.6 kD. Subcellular localization analysis showed that OTX2 localized to the nucleus. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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<p>Dateki et al. (2010) noted that the OTX2 gene contains 5 exons. The first 2 exons are noncoding. </p>
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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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<p>Kastury et al. (1994) mapped the human OTX2 gene to 14q21-q22 by fluorescence in situ hybridization using a cosmid containing the gene. </p><p>Wyatt et al. (2008) noted that the OTX2 gene maps to chromosome 14q22.3. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</h4>
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<p>Boncinelli et al. (1993) showed that Otx2 is expressed in the dorsal and most of the ventral regions of the telencephalon, diencephalon, and mesencephalon of developing mouse brain embryos. Its pattern of expression is wider than that of Otx1 (600036). Developmentally, Otx2 is expressed first, followed by Otx1, Emx2 (600035), and finally by Emx1 (600034). </p><p>Florell et al. (1996) described the association of aprosencephaly, absence of optic chiasm, absent mesencephalon, poorly formed metencephalon, and severely dysplastic cerebellum in 2 sibs; see 601374. Although this complex matched the expression profile of the OTX2 gene, no sequence variations of this gene were identified in the tissues of these fetuses. </p><p>Tenascin-C (TNC; 187380), an extracellular matrix glycoprotein with time- and site-restricted expression during CNS development, has binding sites for neural cells and supports neuronal migration and neurite formation. Gherzi et al. (1997) found that the TNC gene is subject to transcriptional control by OTX2. In cotransfected mammalian cells, OTX2 directly bound with high affinity to a motif in the human TNC promoter and reduced the transcriptional activity of the TNC promoter. </p><p>The Gnrh gene (152760) is expressed exclusively in a highly restricted population of approximately 800 neurons in the mediobasal hypothalamus in the mouse. The Otx2 homeoprotein colocalizes with Gnrh in embryonic mouse brain. Kelley et al. (2000) identified a highly conserved bicoid-related Otx target sequence within the proximal promoter region of the Gnrh gene from several species. This element from the rat Gnrh promoter binds baculovirus-expressed Otx2 protein and Otx2 protein in nuclear extracts of a hypothalamic Gnrh-expressing mouse neuronal cell line, GT1-7. Transient transfection assays indicated that the Gnrh promoter Otx/bicoid site is required for specific expression of the Gnrh gene in GT1-7 cells. Thus, the Gnrh proximal promoter is regulated by the Otx2 homeoprotein. The authors concluded that Otx2 is important in the development of the Gnrh neuron and/or in the maintenance of Gnrh expression in the adult mouse hypothalamus. </p><p>Using a transgenic mouse strain under conditional Otx2 gene ablation, Nishida et al. (2003) found that Otx2 deficiency converted differentiating photoreceptor cells to amacrine-like neurons, reflecting a change in progenitor cell fate, and led to a total lack of pinealocytes in the pineal gland. Expression studies suggested that Otx2 is a direct upstream regulator of another cone-rod homeobox-containing gene, Crx (602225), via binding to specific consensus sequences in the Crx promoter. The findings identified Otx2 as a key regulatory gene in photoreceptor cell development. </p><p>Martinez-Morales et al. (2003) showed that mouse Otx2, like Mitf (156845), could induce the pigmented phenotype in quail neural retinal cells. Otx2 specifically bound to a bicoid motif present in the promoter regions of genes encoding melanosome glycoproteins, leading to their transactivation, and induction was enhanced by Mitf. Otx2 colocalized with Mitf in the nuclei of retinal pigmented cells, and the 2 proteins interacted in vitro. Because Otx2 and Mitf did not appear to regulate each other's expression, Martinez-Morales et al. (2003) proposed that the 2 transcription factors operate at the same hierarchical level to establish the identity of retinal pigment epithelium. </p><p>Akagi et al. (2004) reported that CRX and OTX2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells of adult rat. More than 90% of the CRX- and OTX2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells from embryonic rat expressed rod opsin. At least 2 additional key components of the phototransduction cascade, recoverin (179618) and G-delta-T1, were expressed by CRX- and OTX2-transfected iris-derived cells. Akagi et al. (2004) concluded that CRX and OTX2 induced phenotype generation in cells derived from iris or ciliary tissue, which may suggest an approach to photoreceptor cell preparation for retinal transplantation. </p><p>Hever et al. (2006) reviewed the expression patterns and complex interactions of 3 genes associated with the development of the eye, SOX2 (184429), OTX2, and PAX6 (607108), noting that these interactions may explain the significant phenotypic overlap between mutations at these 3 loci. </p><p>In studies in Xenopus oocytes, Danno et al. (2008) demonstrated specific binding of endogenous OTX2 and SOX2 proteins to a conserved noncoding sequence (CNS1) located approximately 2 kb upstream of the RAX (601881) promoter; reporter assays in Xenopus and HEK93T cells revealed that OTX2 and SOX2 synergistically activated RAX transcription via CNS1. GST pull-down and coimmunoprecipitation assays showed that OTX2 and SOX2 physically interacted, and this interaction was affected by missense mutations located in helices 2 and 3 of the SOX2 HMG domain (R74P, 184429.0008; L97P, 184429.0004, respectively), resulting in reduced induction of transcription via RAX CNS1. Danno et al. (2008) concluded that direct interaction between OTX2 and SOX2 proteins coordinate RAX expression in eye development. </p><p>Panman et al. (2014) found that Sox6 (607257), Otx2, and Nolz1 (ZNF503; 613902) were selectively expressed in distinct subpopulations of mouse embryonic and adult midbrain dopamine (mDA) neurons that were at the neural progenitor cell stage. Sox6 selectively localized to substantia nigra pars compacta (SNc) mDA neurons, whereas Otx2 and Nolz1 localized to a subset of ventral tegmental area (VTA) mDA neurons. Otx2 restricted Sox6 expression in mDA neuron progenitors and suppressed Sox6 expression in postmitotic SNc mDA neurons. Sox6, on the other hand, suppressed VTA-specific characteristics in mDA neurons, promoted SNc-specific differentiation of mDA neurons, and maintained the characteristics of postmitotic SNc neurons. Immunohistochemical analysis showed that SOX6 expression in human mDA neurons appeared to recapitulate the characteristics seen in mice. </p><p>Early life stress increases risk for depression. Pena et al. (2017) established a 2-hit stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA), a brain reward region, to be in a depression-like state. Pena et al. (2017) identified a role for the developmental transcription factor Otx2 as an upstream mediator of these enduring effects. Transient juvenile, but not adult, knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. Pena et al. (2017) concluded that their work established a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</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><strong><em>Syndromic Microphthalmia 5</em></strong></p><p>
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Using a candidate gene approach, Ragge et al. (2005) analyzed 333 patients with ocular malformation spectrum defects and identified heterozygous mutations in the OTX2 gene in 11 affected individuals from 8 families (see MCOPS5, 610125). In 2 families, the mutations occurred de novo in severely affected offspring (600037.0001 and 600037.0002, respectively), and in 2 other families, the mutations were inherited from a gonosomal mosaic parent (600037.0003 and 600037.0004, respectively). Ragge et al. (2005) stated that data from these 4 families supported a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. The other 4 families displayed complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. </p><p>Wyatt et al. (2008) analyzed the OTX2 gene in 165 patients with ocular malformations, primarily clinical anophthalmia, microphthalmia, and/or coloboma, and identified heterozygosity for 2 whole gene deletions, involving OTX2 and several other genes, and 2 nonsense and 2 frameshift mutations, in 8 patients from 6 families. </p><p>In an 8.5-year-old Japanese girl with bilateral clinical anophthalmia, short stature, developmental delay, and partial growth hormone deficiency, who was negative for mutation in the HESX1 (601802) and POU1F1 (173110) genes, Dateki et al. (2008) identified a de novo heterozygous frameshift mutation in the OTX2 gene (600037.0005). </p><p>In a 6-year-old Japanese boy with bilateral clinical anophthalmia, short stature, and combined pituitary hormone deficiency, Tajima et al. (2009) identified a de novo heterozygous frameshift mutation in the OTX2 gene (600037.0007). </p><p>Dateki et al. (2010) analyzed the OTX2 gene in 16 patients with ocular anomalies, short stature, and pituitary dysfunction, 12 patients with ocular anomalies with or without short stature in whom pituitary function was not investigated, and 66 patients with pituitary dysfunction without ocular anomalies. The patients were negative for mutation in genes known to be associated with their respective phenotypes. Dateki et al. (2010) identified 3 heterozygous OTX2 truncation mutations in 4 unrelated patients (see, e.g., 600037.0009 and 600037.0010) and a microdeletion involving the OTX2 gene in 1 patient. The authors concluded that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations. </p><p>In a 13.5-year-old boy with unilateral clinical anophthalmia, short stature, and isolated GH deficiency, Ashkenazi-Hoffnung et al. (2010) analyzed the HESX1, SOX2 (184429), and OTX2 genes, and identified heterozygosity for a missense mutation in the OTX2 DNA-binding domain (600037.0011). </p><p>In a large 4-generation French family in which 17 individuals had microphthalmia or clinical anophthalmia, Chassaing et al. (2012) identified a heterozygous 1-bp deletion in the OTX2 gene (316delC; 600037.0012) that segregated with disease. Included in the pedigree were 3 deceased offspring with otocephaly (see 202650), from whom DNA was unavailable; however, a deceased male infant with an intermediate phenotype was also found to be heterozygous for the 1-bp deletion. Because of the phenotypic variability observed in the French family, Chassaing et al. (2012) screened 5 additional candidate genes known to play a role in vertebrate otocephalic malformations, including PRRX1 (167420), but did not detect any likely pathogenic variants. The authors concluded that loss-of-function OTX2 mutations do not sufficiently explain the complex anatomic defects in patients with otocephaly/dysgnathia, suggesting the requirement for a second genetic hit. </p><p>In a mother with unilateral severe microphthalmia and her male fetus with agnathia-otocephaly complex, Patat et al. (2013) identified heterozygosity for a nonsense mutation in the OTX2 gene (R97X; 600037.0013). The fetus also carried a heterozygous synonymous OTX2 variant (c.525C-G) that was inherited from his asymptomatic father; however, the authors stated that it was unlikely that the silent variant explained the intrafamilial phenotypic variability. </p><p><strong><em>Combined Pituitary Hormone Deficiency 6</em></strong></p><p>
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In 19 patients with hypopituitarism (CPHD6; 613986), Diaczok et al. (2008) analyzed 8 genes encoding pituitary-specific transcription factors, including HESX1, LHX3 (600577), LHX4 (602146), OTX2, PITX2 (601542), POU1F1, PROP1 (601538), and SIX6 (606326), and identified heterozygosity for a missense mutation in the OTX2 gene (600037.0006) in 2 unrelated patients. One was a 6-year-old boy with deficiency of GH, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), who on MRI had an ectopic neurohypophysis, along with a hypoplastic adenohypophysis and absent or severely hypoplastic pituitary stalk. The other patient was a 14-year-old girl with deficiency of TSH, ACTH, and GH, in whom MRI at age 2 months showed hypoplasia of the pituitary with a posterior bright spot. Neither patient had midline or optic nerve abnormalities. </p><p><strong><em>Early-Onset Retinal Dystrophy with or without Pituitary Dysfunction</em></strong></p><p>
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Henderson et al. (2009) analyzed DNA samples from 142 patients with Leber congenital amaurosis (LCA; see 204000) or severe childhood-onset retinal dystrophy (RD; see 613341) using an 'LCA chip' involving 8 LCA- and RD-associated genes, as well as screening the OTX2 gene. In a 7-year-old boy with early-onset retinal dystrophy, who was negative for all variants assayed by the LCA chip, they identified heterozygosity for a de novo nonsense mutation in the OTX2 gene (600037.0008). The patient also had failure to thrive and subsequent short stature (see 610125), and growth hormone deficiency was suggested indirectly due to low levels of IGF1 (147440) and IGFBP3 (146732). Henderson et al. (2009) stated that the phenotypic spectrum observed in this patient was consistent with the assigned multiple roles of OTX2 in the development and function of both the retinal pigment epithelium (RPE) and neural retina, as well as in the pituitary. </p><p>In affected individuals from 2 Caucasian Canadian families segregating autosomal dominant pattern retinal dystrophy without pituitary dysfunction, Vincent et al. (2014) identified heterozygosity for a missense mutation in the OTX2 gene (E79K; 600037.0014). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>The mid/hindbrain junction can act as an organizer to direct the development of the midbrain and anterior hindbrain. In mice, Otx2 is expressed in the forebrain and midbrain and Gbx2 (601135) is expressed in the anterior hindbrain, with a shared border at the level of the mid/hindbrain organizer. Millet et al. (1999) demonstrated that in Gbx2 -/- mutants, the earliest phenotype is a posterior expansion of the Otx2 domain during early somite stages. Furthermore, organizer genes are expressed at the shifted Otx2 border, but not in a normal spatial relationship. To test whether Gbx2 is sufficient to position the mid/hindbrain organizer, Millet et al. (1999) transiently expressed Gbx2 in the caudal Otx2 domain and found that the Otx2 caudal border was indeed shifted rostrally, and a normal-appearing organizer formed at this new Otx2 border. Transgenic embryos then showed an expanded hindbrain and a reduced midbrain at embryonic day 9.5 to 10. Millet et al. (1999) proposed that the formation of a normal mid/hindbrain organizer depends on a sharp Otx2 caudal border and that Gbx2 is required to position and sharpen this border. </p><p>By ectopically expressing Otx2 in the murine presumptive anterior hindbrain using a knockin strategy into the En1 (131290) locus, Broccoli et al. (1999) investigated whether the caudal limit of Otx2 expression is instrumental in positioning the isthmic organizer (midbrain/hindbrain junction) and in specifying midbrain versus hindbrain fate. Transgenic offspring displayed a cerebellar ataxia. Morphologic and histologic studies of adult transgenic brains revealed that most of the anterior cerebellar vermis is missing, whereas the inferior colliculus is complementarily enlarged. During early neuronal pattern formation, expression of the midbrain markers Wnt1 (164820) and ephrin A5 (601535), the isthmic organizer markers Pax2 (167409) and Fgf8 (600483), and the hindbrain marker Gbx2 are shifted caudally in the presumptive hindbrain territory. Broccoli et al. (1999) concluded that the caudal limit of Otx2 expression is sufficient for positioning the isthmic organizer and encoding caudal midbrain fate within the mid/hindbrain domain. </p><p>Kimura-Yoshida et al. (2005) found that Otx2 deficiency resulted in defective conversion of the mouse embryonic axis from the proximal-distal orientation to a prospective anterior-posterior polarity. Defective axis conversion was rescued by expression of Dkk1 (605189), a Wnt (see WNT1; 164820) antagonist, or following removal of 1 copy of the beta-catenin gene (see CTNNB1; 116806). Furthermore, the asymmetric distribution of beta-catenin localization was impaired in Otx2-deficient embryos. </p><p>Chassaing et al. (2012) transiently suppressed the zebrafish ortholog of OTX2. At 5 days postfertilization, the zebrafish showed mild microphthalmia and shortening of the pharyngeal skeleton that increased in penetrance in a dose-dependent manner. Combined suppression of otx2 and other otocephaly-associated genes, including prrx1 (167420), pgap1 (611655), and msx1 (142983), demonstrated a synergistic exacerbation of the phenotypes: pairwise suppression resulted in increased mortality and a new class of embryos that displayed severe microphthalmia, eye fusion along the midline, and severe disorganization of mandibular cartilage. Chassaing et al. (2012) concluded that suppression of otx2, in combination with loss of function of other loci contributing to otocephaly phenotypes, can modulate phenotypic severity in the manifestation of craniofacial malformations. </p><p>In mouse, Zhang et al. (2018) showed that downregulation of Otx2 precedes the initiation of the primordial germ cell (PGC) program both in vitro and in vivo. Deletion of Otx2 in vitro markedly increased the efficiency of PGC-like cell differentiation and prolonged the period of PGC competence. In the absence of Otx2 activity, differentiation of PGC-like cells became independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC transcription factor Blimp1 (603423). Deletion of Otx2 in vivo increased primordial germ cell numbers. Zhang et al. (2018) concluded that OTX2 functions repressively upstream of PGC transcription factors, acting as a roadblock to limit entry of epiblast cells to the germline to a small window in space and time, thereby ensuring correct numerical segregation of germline cells from the soma. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>14 Selected Examples):</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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MICROPHTHALMIA, SYNDROMIC 5</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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OTX2, 2-BP INS, 464GC
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<br />
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SNP: rs786205873,
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ClinVar: RCV000010123
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</span>
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<span class="mim-text-font">
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<p>In a boy with right clinical anophthalmia and left microphthalmia and associated features (MCOPS5; 610125), Ragge et al. (2005) identified heterozygosity for a de novo 2-bp insertion (464GC) in exon 5 of the OTX2 gene, predicted to result in a nonsense codon 22 amino acids downstream. Based on numbering from the first residue of the initiation codon as +1, the 635insGC mutation is renumbered as 464insGC, and exon numbering includes the first 2 noncoding exons (Dateki et al., 2008). The patient also had left-sided persistent pupillary membrane, iris coloboma, high hypermetropia, and chorioretinal coloboma. MRI scan at age 1 month showed partial agenesis of the corpus callosum with a normal-sized pituitary gland, absent right optic nerve and small left optic nerve, thin chiasm, and malformation of the hippocampi bilaterally. Examination at age 4 years revealed marked developmental delay, generalized hypotonia, increased joint laxity, and microcephaly. Neither the parents nor the unaffected brother carried the mutation. </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>.0002 MICROPHTHALMIA, SYNDROMIC 5</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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OTX2, ARG89GLY
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<br />
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SNP: rs104894464,
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ClinVar: RCV000010124
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<span class="mim-text-font">
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<p>In a boy with asymmetric microphthalmia and associated features (MCOPS5; 610125), Ragge et al. (2005) identified heterozygosity for a de novo 265C-G transversion in exon 5 of the OTX2 gene, resulting in an arg89-to-gly (R89G) substitution in the homeodomain. On an MRI at age 3 weeks, there was bilateral optic nerve aplasia, the chiasm was not visualized, and there was thinning of the corpus callosum anteriorly; when repeated at 2 years of age, no optic chiasm was seen but the corpus callosum appeared normal. Horizontal corneal diameters were 6.5 mm and 8.0 mm on the right and left, respectively. The only systemic abnormalities at birth were midline dermoid cysts on the forehead and nasal bridge. Cognitive and language skills were normal at age 4. </p><p>Based on numbering from the initiation codon, 346C-G is renumbered as 265C-G, and exon numbering includes the first 2 noncoding exons (Dateki et al., 2008). </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>.0003 MICROPHTHALMIA, SYNDROMIC 5</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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OTX2, 1-BP DEL, 81C
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<br />
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SNP: rs786205874,
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ClinVar: RCV000010125
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<div>
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<span class="mim-text-font">
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<p>In a female infant with bilateral severe microphthalmia and associated features (MCOPS5; 610125), Ragge et al. (2005) identified heterozygosity for a 1-bp deletion (81delC) in exon 3 of the OTX2 gene, predicted to result in a termination codon in exon 4. CT scan revealed a thickened septum pellucidum and slightly enlarged lateral ventricles. A fetus, terminated after ultrasound revealed bilateral microphthalmia and agenesis of the corpus callosum, also carried the mutation. The phenotypically normal mother was found to be a gonosomal mosaic carrier of the mutation. </p><p>Based on numbering from the first residue of initiation codon as +1, the 252delC mutation is renumbered as 81delC, and exon numbering includes the first 2 noncoding exons (Dateki et al., 2008). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MICROPHTHALMIA, SYNDROMIC 5</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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OTX2, TYR179TER
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<br />
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SNP: rs104894465,
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gnomAD: rs104894465,
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ClinVar: RCV000010126
|
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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 sister and brother with bilateral microphthalmia and associated features (MCOPS5; 610125), Ragge et al. (2005) identified heterozygosity for a 537T-A transversion in exon 5 of the OTX2 gene, resulting in a tyr179-to-ter (Y179X) substitution in the C-terminal domain. The sister also had bilateral colobomas and microcornea, left-sided cataract, bilateral fifth finger clinodactyly, severe learning difficulties, and a seizure disorder. The brother, who had borderline microphthalmic eyes, was given a diagnosis of Leber congenital amaurosis (LCA; see 204000) at birth; examination at age 26 years revealed pale optic discs, thin retinal vessels, atrophic maculae, and large clumps of pigment in the midperiphery, consistent with the diagnosis of LCA. ERG was absent, and he had nystagmus, bilateral peripheral anterior synechiae, and a right-sided hearing loss. The mother was found to be a gonosomal mosaic carrier of the mutation; examination of her eyes revealed retinal dystrophy comparable to that seen in her son, night blindness, and extensive peripheral field loss bilaterally. </p><p>Based on numbering from the initiation codon as +1, 708T-A is renumbered as 537T-A, and exon numbering includes the first 2 noncoding exons (Dateki et al., 2008). </p>
|
|
</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>
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<span class="mim-font">
|
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<strong>.0005 MICROPHTHALMIA, SYNDROMIC 5</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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OTX2, 1-BP INS, 402C
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<br />
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SNP: rs1555350223,
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ClinVar: RCV000594111, RCV000596696, RCV003530088
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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 an 8.5-year-old Japanese girl with bilateral clinical anophthalmia, short stature, developmental delay, and partial growth hormone deficiency (MCOPS5; 610125), Dateki et al. (2008) identified heterozygosity for a de novo 1-bp insertion (402insC) in exon 5 of the OTX2 gene, predicted to cause a frameshift and premature termination codon resulting in retention of the homeodomain but loss of the transactivation domain as well as the SIWSPA motif. The mutation was not found in either parent. Functional studies showed that both wildtype and mutant protein localized to the nucleus; however, wildtype OTX2 markedly transactivated the reporters for the IRBP (180290), HESX1 (601802), and POU1F1 (173110) genes, whereas mutant OTX2 barely retained transactivation activities and had no dominant-negative effects. </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>.0006 PITUITARY HORMONE DEFICIENCY, COMBINED, 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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OTX2, ASN233SER
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<br />
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|
|
SNP: rs370761964,
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gnomAD: rs370761964,
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|
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ClinVar: RCV000022923
|
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|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 2 unrelated patients with multiple pituitary hormone deficiencies (CPHD6; 613986), Diaczok et al. (2008) identified heterozygosity for a 698A-G transition in exon 5 of the OTX2 gene, resulting in an asn233-to-ser (N233S) substitution in the transcription factor region. Electrophoretic mobility shift assay (EMSA) with murine Otx2 demonstrated that both wildtype and mutant Otx2 bound equally well to 2 specific sites in the 5-prime flanking region of the HESX1 gene (601802). Functional studies in 293T cells showed that the mutant Otx2 had a dominant negative effect on the proximal promoter region of HESX1 and a multiple bicoid binding site reporter construct, and studies in the GH-producing GH3 cells showed that N233S Otx2 repressed reporter expression. Diaczok et al. (2008) concluded that the heterozygous N233S OTX2 mutation acts as a dominant inhibitor of the HESX1 gene. </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>.0007 MICROPHTHALMIA, SYNDROMIC 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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OTX2, 2-BP INS, 576CT
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<br />
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|
SNP: rs1566623121,
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|
|
ClinVar: RCV000022924
|
|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with bilateral clinical anophthalmia, short stature, and combined pituitary hormone deficiency (MCOPS5; 610125), Tajima et al. (2009) identified a de novo heterozygous 2-bp insertion (576insCT) in exon 5 of the OTX2 gene, causing a frameshift and premature termination codon, resulting in a protein lacking the C-terminal region. The mutation was not found in the unaffected parents or in 50 Japanese controls. Functional analysis in mice revealed that the mutant protein localized to the nucleus, but activation of the promoters of the HESX1 (601802) and POU1F1 (173110) genes was absent or less than 50% of wildtype, respectively. </p>
|
|
</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>.0008 RETINAL DYSTROPHY, EARLY-ONSET, WITH PITUITARY DYSFUNCTION</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
OTX2, SER138TER
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|
<br />
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|
|
SNP: rs786205879,
|
|
|
|
|
|
|
|
ClinVar: RCV000022925
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with severe childhood-onset retinal dystrophy and growth hormone deficiency (see 610125), Henderson et al. (2009) identified heterozygosity for a de novo 413C-G transversion in the OTX2 gene, resulting in a ser138-to-ter (S138X) substitution. The patient, who was noted to have poor vision and nyctalopia during his first year of life, also had failure to thrive and growth hormone deficiency. The mutation was not found in his unaffected parents or in 181 controls. </p>
|
|
</span>
|
|
</div>
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|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MICROPHTHALMIA, SYNDROMIC 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
OTX2, 16-BP DEL, NT221
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|
|
<br />
|
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|
|
SNP: rs1566624472,
|
|
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|
|
|
|
|
ClinVar: RCV000022926
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old boy with right clinical anophthalmia and left microphthalmia, who had developmental delay, short stature, and growth hormone deficiency (MCOPS5; 610125), Dateki et al. (2010) identified heterozygosity for a de novo 16-bp deletion (221_236del) in exon 4 of the OTX2 gene, predicted to cause a frameshift and premature termination codon. The deletion was not found in the unaffected parents or in 100 controls. Functional analysis revealed that the mutant protein had no transactivation functions for 4 promoters that were transactivated by wildtype OTX2; no dominant-negative effect was observed. Brain MRI revealed pituitary hypoplasia and ectopic posterior pituitary. The patient also had right-sided retractile testis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MICROPHTHALMIA, SYNDROMIC 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTX2, GLY188TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514463,
|
|
|
|
|
|
|
|
ClinVar: RCV000022927, RCV001857357
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old boy and an unrelated 10-year-old boy, both of whom had bilateral microphthalmia and developmental delay (MCOPS5; 610125), Dateki et al. (2010) identified heterozygosity for a 562G-T transversion in exon 5 of the OTX2 gene, predicted to cause a gly188-to-ter (G188X) substitution. The mutation was not found in 100 controls; the parents refused molecular studies. Functional analysis revealed that the mutant protein had reduced transactivation function (approximately 50% of wildtype) for the 4 promoters tested, with no dominant-negative effect. The 15-year-old patient had deficiency of the pituitary hormones GH, TSH, PRL, LH, and FSH, and brain MRI revealed pituitary hypoplasia and ectopic posterior pituitary. The 10-year-old patient, who also had seizures, had 'no discernible pituitary dysfunction' and did not undergo brain MRI. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MICROPHTHALMIA, SYNDROMIC 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTX2, ARG90SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1566623392,
|
|
|
|
|
|
|
|
ClinVar: RCV000022928
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 13.5-year-old boy of Sephardic Jewish descent who had unilateral clinical anophthalmia, short stature, and isolated GH deficiency (MCOPS5; 610125), Ashkenazi-Hoffnung et al. (2010) identified heterozygosity for a 270A-T transversion in exon 3 of the OTX2 gene, resulting in an arg90-to-ser (R90S) substitution in the DNA-binding homeodomain. His father, who had short stature but normal eye structure and unknown endocrine status, was also heterozygous for the mutation. The mutation was not present in the unaffected mother or an unaffected brother, and had not previously been found in 261 controls (Ragge et al., 2005; Wyatt et al., 2008). Functional analysis revealed that the R90S mutation did not affect the expression or nuclear localization of the protein, but inhibited its DNA-binding activity as well as its transactivation capability, thus rendering it nonfunctional. No dominant-negative effect was observed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MICROPHTHALMIA, SYNDROMIC 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTX2, 1-BP DEL, 316C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786205884,
|
|
|
|
|
|
|
|
ClinVar: RCV000170470
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large 4-generation French family in which 17 individuals had microphthalmia or clinical anophthalmia, 3 of whom also exhibited moderate to severe mental retardation (MCOPS5; 610125), Chassaing et al. (2012) identified a heterozygous 1-bp deletion (c.316delC, NM_021728.2) in the OTX2 gene, causing a frameshift predicted to result in premature termination (Gln106AsnfsTer11) within the glutamine stretch. Included in the pedigree were 3 deceased offspring with otocephaly, from whom DNA was unavailable; however, 2 were sibs born of an affected mother who carried the deletion, and another deceased male infant who exhibited clinical features overlapping both microphthalmia and otocephaly was also found to be heterozygous for the 1-bp deletion. Chassaing et al. (2012) stated that loss-of-function OTX2 mutations do not sufficiently explain the complex anatomic defects in patients with otocephaly/dysgnathia, suggesting the requirement for a second genetic hit. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MICROPHTHALMIA, SYNDROMIC 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTX2, ARG97TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894464,
|
|
|
|
|
|
|
|
ClinVar: RCV000170471, RCV001558575
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mother with unilateral severe microphthalmia and her male fetus with agnathia-otocephaly complex (see MCOPS5, 610125), Patat et al. (2013) identified heterozygosity for a c.289C-T transition (c.289C-T, NM_021728.2) in the OTX2 gene, resulting in an arg97-to-ter (R97X) substitution. The fetus also carried a heterozygous synonymous OTX2 variant (c.525C-G) that was inherited from his asymptomatic father; however, the authors stated that it was unlikely that the silent variant explained the intrafamilial phenotypic variability. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 RETINAL DYSTROPHY, EARLY-ONSET, WITHOUT PITUITARY DYSFUNCTION</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTX2, GLU79LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786205224,
|
|
|
|
|
|
|
|
ClinVar: RCV000170472, RCV000494571
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 2 Caucasian Canadian families segregating autosomal dominant pattern retinal dystrophy without pituitary dysfunction (see 610125), Vincent et al. (2014) identified heterozygosity for a c.235G-A transition (c.235G-A, NM_001270523.1) in exon 4 of the OTX2 gene, resulting in a glu79-to-lys (E79K) substitution at a highly conserved residue in the homeobox domain. Haplotype analysis revealed a 19.68-cM shared haplotype between SNPs rs17107459 and rs710050; the number of generations between a common ancestor and affected individuals in the youngest generation in each family was estimated to be 5, making them fourth cousins. Of the 7 patients who underwent ocular examination, 3 exhibited a butterfly pattern of retinal dystrophy, 2 showed a grouped pigmentation pattern, 1 showed an annular pattern, and 1 showed only a dull foveal reflex with no apparent pattern. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M.
|
|
<strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong>
|
|
Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.
|
|
|
|
|
|
[PubMed: 15557469]
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|
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|
|
[Full Text: https://doi.org/10.1167/iovs.04-0697]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Ashkenazi-Hoffnung, L., Lebenthal, Y., Wyatt, A. W., Ragge, N. K., Dateki, S., Fukami, M., Ogata, T., Phillip, M., Gat-Yablonski, G.
|
|
<strong>A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency.</strong>
|
|
Hum. Genet. 127: 721-729, 2010.
|
|
|
|
|
|
[PubMed: 20396904]
|
|
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|
|
[Full Text: https://doi.org/10.1007/s00439-010-0820-9]
|
|
|
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boncinelli, E., Gulisano, M., Broccoli, V.
|
|
<strong>Emx and Otx homeobox genes in the developing mouse brain.</strong>
|
|
J. Neurobiol. 24: 1356-1366, 1993.
|
|
|
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|
|
[PubMed: 7901323]
|
|
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|
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[Full Text: https://doi.org/10.1002/neu.480241008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Broccoli, V., Boncinelli, E., Wurst, W.
|
|
<strong>The caudal limit of Otx2 expression positions the isthmic organizer.</strong>
|
|
Nature 401: 164-168, 1999.
|
|
|
|
|
|
[PubMed: 10490025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/43670]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chassaing, N., Sorrentino, S., Davis, E. E., Martin-Coignard, D., Iacovelli, A., Paznekas, W., Webb, B. D., Faye-Petersen, O., Encha-Razavi, F., Lequeux, L., Vigouroux, A., Yesilyurt, A., and 12 others.
|
|
<strong>OTX2 mutations contribute to the otocephaly-dysgnathia complex.</strong>
|
|
J. Med. Genet. 49: 373-379, 2012.
|
|
|
|
|
|
[PubMed: 22577225]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2012-100892]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Danno, H., Michiue, T., Hitachi, K., Yukita, A., Ishiura, S., Asashima, M.
|
|
<strong>Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 5408-5413, 2008.
|
|
|
|
|
|
[PubMed: 18385377]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0710954105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dateki, S., Fukami, M., Sato, N., Muroya, K., Adachi, M., Ogata, T.
|
|
<strong>OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters.</strong>
|
|
J. Clin. Endocr. Metab. 93: 3697-3702, 2008.
|
|
|
|
|
|
[PubMed: 18628516]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2008-0720]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dateki, S., Kosaka, K., Hasegawa, K., Tanaka, H., Azuma, N., Yokoya, S., Muroya, K., Adachi, M., Tajima, T., Motomura, K., Kinoshita, E., Moriuchi, H., Sato, N., Fukami, M., Ogata, T.
|
|
<strong>Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype.</strong>
|
|
J. Clin. Endocr. Metab. 95: 756-764, 2010.
|
|
|
|
|
|
[PubMed: 19965921]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2009-1334]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Diaczok, D., Romero, C., Zunich, J., Marshall, I., Radovick, S.
|
|
<strong>A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 93: 4351-4359, 2008.
|
|
|
|
|
|
[PubMed: 18728160]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2008-1189]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Florell, S. R., Townsend, J. J., Klatt, E. C., Pysher, T. J., Coffin, C. M., Wittwer, C. T., Viskochil, D. H.
|
|
<strong>Aprosencephaly and cerebellar dysgenesis in sibs.</strong>
|
|
Am. J. Med. Genet. 63: 542-548, 1996.
|
|
|
|
|
|
[PubMed: 8826432]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960628)63:4<542::AID-AJMG6>3.0.CO;2-Q]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gherzi, R., Briata, P., Boncinelli, E., Ponassi, M., Querze, G., Viti, F., Corte, G., Zardi, L.
|
|
<strong>The human homeodomain protein OTX2 binds to the human tenascin-C promoter and trans-represses its activity in transfected cells.</strong>
|
|
DNA Cell Biol. 16: 559-567, 1997.
|
|
|
|
|
|
[PubMed: 9174161]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1089/dna.1997.16.559]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Henderson, R. H., Williamson, K. A., Kennedy, J. S., Webster, A. R., Holder, G. E., Robson, A. G., FitzPatrick, D. R., van Heyningen, V., Moore, A. T.
|
|
<strong>A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.</strong>
|
|
Molec. Vision 15: 2442-2447, 2009.
|
|
|
|
|
|
[PubMed: 19956411]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hever, A. M., Williamson, K. A., van Heyningen, V.
|
|
<strong>Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2.</strong>
|
|
Clin. Genet. 69: 459-470, 2006.
|
|
|
|
|
|
[PubMed: 16712695]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00619.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kastury, K., Druck, T., Huebner, K., Barletta, C., Acampora, D., Simeone, A., Faiella, A., Boncinelli, E.
|
|
<strong>Chromosome locations of human EMX and OTX genes.</strong>
|
|
Genomics 22: 41-45, 1994.
|
|
|
|
|
|
[PubMed: 7959790]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1343]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kelley, C. G., Lavorgna, G., Clark, M. E., Boncinelli, E., Mellon, P. L.
|
|
<strong>The Otx2 homeoprotein regulates expression from the gonadotropin-releasing hormone proximal promoter.</strong>
|
|
Molec. Endocr. 14: 1246-1256, 2000.
|
|
|
|
|
|
[PubMed: 10935548]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/mend.14.8.0509]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kimura-Yoshida, C., Nakano, H., Okamura, D., Nakao, K., Yonemura, S., Belo, J. A., Aizawa, S., Matsui, Y., Matsuo, I.
|
|
<strong>Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm.</strong>
|
|
Dev. Cell 9: 639-650, 2005.
|
|
|
|
|
|
[PubMed: 16256739]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.devcel.2005.09.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martinez-Morales, J. R., Dolez, V., Rodrigo, I., Zaccarini, R., Leconte, L., Bovolenta, P., Saule, S.
|
|
<strong>OTX2 activates the molecular network underlying retina pigment epithelium differentiation.</strong>
|
|
J. Biol. Chem. 278: 21721-21731, 2003.
|
|
|
|
|
|
[PubMed: 12663655]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M301708200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E., Joyner, A. L.
|
|
<strong>A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer.</strong>
|
|
Nature 401: 161-164, 1999.
|
|
|
|
|
|
[PubMed: 10490024]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/43664]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., Furukawa, T.
|
|
<strong>Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.</strong>
|
|
Nature Neurosci. 6: 1255-1263, 2003.
|
|
|
|
|
|
[PubMed: 14625556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn1155]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Panman, L., Papathanou, M., Laguna, A., Oosterveen, T., Volakakis, N., Acampora, D., Kurtsdotter, I., Yoshitake, T., Kehr, J., Joodmardi, E., Muhr, J., Simeone, A., Ericson, J., Perlmann, T.
|
|
<strong>Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons.</strong>
|
|
Cell Rep. 8: 1018-1025, 2014.
|
|
|
|
|
|
[PubMed: 25127144]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.celrep.2014.07.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Patat, O., van Ravenswaaij-Arts, C. M. A., Tantau, J., Corsten-Janssen, N., van Tintelen, J. P., Dijkhuizen, T., Kaplan, J., Chassaing, N.
|
|
<strong>Otocephaly-dysgnathia complex: description of four cases and confirmation of the role of OTX2.</strong>
|
|
Molec. Syndromol. 4: 302-305, 2013.
|
|
|
|
|
|
[PubMed: 24167467]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000353727]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pena, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., Goodman, E., Neve, R. L., Shen, L., Nestler, E. J.
|
|
<strong>Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.</strong>
|
|
Science 356: 1185-1188, 2017.
|
|
|
|
|
|
[PubMed: 28619944]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aan4491]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ragge, N. K., Brown, A. G., Poloschek, C. M., Lorenz, B., Henderson, R. A., Clarke, M. P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J. P., Ruddle, P., Hurst, J., and 9 others.
|
|
<strong>Heterozygous mutations of OTX2 cause severe ocular malformations.</strong>
|
|
Am. J. Hum. Genet. 76: 1008-1022, 2005. Note: Erratum: Am. J. Hum. Genet. 77: 334 only, 2005.
|
|
|
|
|
|
[PubMed: 15846561]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/430721]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Simeone, A., Acampora, D., Gulisano, M., Stornaiuolo, A., Boncinelli, E.
|
|
<strong>Nested expression domains of four homeobox genes in developing rostral brain.</strong>
|
|
Nature 358: 687-690, 1992.
|
|
|
|
|
|
[PubMed: 1353865]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/358687a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tajima, T., Ohtake, A., Hoshino, M., Amemiya, S., Sasaki, N., Ishizu, K., Fujieda, K.
|
|
<strong>OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.</strong>
|
|
J. Clin. Endocr. Metab. 94: 314-319, 2009.
|
|
|
|
|
|
[PubMed: 18854396]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2008-1219]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vincent, A., Forster, N., Maynes, J. T., Paton, T. A., Billingsley, G., Roslin, N. M., Ali, A., Sutherland, J., Wright, T., Westall, C. A., Paterson, A. D., Marshall, C. R., FORGE Canada Consortium, Heon, E.
|
|
<strong>OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium.</strong>
|
|
J. Med. Genet. 51: 797-805, 2014.
|
|
|
|
|
|
[PubMed: 25293953]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2014-102620]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wyatt, A., Bakrania, P., Bunyan, D. J., Osborne, R. J., Crolla, J. A., Salt, A., Ayuso, C., Newbury-Ecob, R., Abou-Rayyah, Y., Collin, J. R. O., Robinson, D., Ragge, N.
|
|
<strong>Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma.</strong>
|
|
Hum. Mutat. 29: E278-E283, 2008. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 18781617]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20869]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A., Chambers, I.
|
|
<strong>OTX2 restricts entry to the mouse germline.</strong>
|
|
Nature 562: 595-599, 2018.
|
|
|
|
|
|
[PubMed: 30283136]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-018-0581-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
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|
|
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|
|
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|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Bao Lige - updated : 02/04/2020<br>Ada Hamosh - updated : 02/26/2019<br>Ada Hamosh - updated : 01/31/2018<br>Marla J. F. O'Neill - updated : 5/6/2015<br>Marla J. F. O'Neill - updated : 4/27/2011<br>Marla J. F. O'Neill - updated : 6/6/2008<br>Marla J. F. O'Neill - updated : 7/27/2006<br>Marla J. F. O'Neill - updated : 5/16/2006<br>Patricia A. Hartz - updated : 12/21/2005<br>Jane Kelly - updated : 3/3/2005<br>Cassandra L. Kniffin - updated : 3/2/2004<br>John A. Phillips, III - updated : 7/12/2002<br>Ada Hamosh - updated : 2/18/2000<br>Iosif W. Lurie - updated : 8/11/1996<br>Alan F. Scott - updated : 1/29/1996
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Victor A. McKusick : 7/14/1994
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