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Entry
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- *313430 - SRY-BOX 3; SOX3
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- OMIM
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</div>
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</form>
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</div>
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</div>
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<div class="container hidden-print">
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<div class="row">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<div id="mimAlertBanner">
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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">*313430</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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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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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>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#evolution">Evolution</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cytogenetics">Cytogenetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/313430">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">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
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<div class="panel-body small mim-panel-body">
|
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|
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000134595;t=ENST00000370536" 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=6658" 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=313430" 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=ENSG00000134595;t=ENST00000370536" 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_005634" 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_005634" 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=313430" 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
|
|
</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=02432&isoform_id=02432_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/SOX3" 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/468794,530020,938234,8118618,30061556,48429228,62739570,62739572,119608828" 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/P41225" 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">
|
|
<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>
|
|
</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=6658" 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=ENSG00000134595;t=ENST00000370536" 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=SOX3" 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=SOX3" 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+6658" 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/SOX3" 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:6658" 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/6658" 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=chrX&hgg_gene=ENST00000370536.5&hgg_start=140502985&hgg_end=140505069&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:11199" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:11199" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=313430[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=313430[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/SOX3/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/ENSG00000134595" 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.gwascentral.org/search?q=SOX3" 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=SOX3" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/SOX3" 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=SOX3&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/PA36036" 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:11199" 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/FBgn0000411.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:98365" 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/SOX3#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:98365" 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/6658/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=6658" 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=WBGene00004949;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-980526-333" 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">
|
|
<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=SOX3&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> 237683004<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>
|
|
313430
|
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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>
|
|
<span class="mim-font">
|
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|
SRY-BOX 3; SOX3
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
|
<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>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
SRY-RELATED HMG-BOX GENE 3
|
|
</span>
|
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</h4>
|
|
</div>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SOX3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SOX3</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/743?start=-3&limit=10&highlight=743">Xq27.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:140502985-140505069&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'})">X:140,502,985-140,505,069</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=300123,312000" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/743?start=-3&limit=10&highlight=743">
|
|
Xq27.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, X-linked, with isolated growth hormone deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300123"> 300123 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
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|
|
|
|
|
|
|
</tr>
|
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|
|
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|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Panhypopituitarism, X-linked
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/312000"> 312000 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked">XL</abbr>
|
|
|
|
</span>
|
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<p>The mammalian genome contains a family of genes that are related to SRY (<a href="/entry/480000">480000</a>), the testis-determining gene. The homology is restricted to the region of SRY that encodes a DNA-binding motif of the HMG-box class (the DNA-binding domain is called HMG for 'high mobility group'). These genes have been named SOX, for SRY-related HMG-box (see SOX1; <a href="/entry/602148">602148</a>).</p>
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<p><a href="#16" class="mim-tip-reference" title="Stevanovic, M., Lovell-Badge, R., Collignon, J., Goodfellow, P. N. <strong>SOX3 is an X-linked gene related to SRY.</strong> Hum. Molec. Genet. 2: 2013-2018, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111369</a>] [<a href="https://doi.org/10.1093/hmg/2.12.2013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8111369">Stevanovic et al. (1993)</a> cloned and characterized SOX3. A reverse transcription coupled with PCR (RT-PCR) was used to amplify SRY-related transcripts expressed during embryogenesis in human fetal spinal cord. Inspection of fragments detected by one of them showed a difference between males and females, suggesting a SOX gene located on the X chromosome. Isolation and sequencing of the gene showed 97.2% similarity to the protein encoded by the mouse Sox3 gene which is also located on the X chromosome. The RACE (rapid amplification of complementary DNA ends) method was used to define the 3-prime end of the transcript and to confirm that the SOX3 gene is expressed. Using the sensitive RT-PCR assay, SOX3 gene transcripts were detected in several fetal tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8111369" 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="mim-changed mim-change"><p><a href="#4" class="mim-tip-reference" title="Collignon, J., Sockanathan, S., Hacker, A., Cohen-Tannoudji, M., Norris, D., Rastan, S., Stevanovic, M., Goodfellow, P. N., Lovell-Badge, R. <strong>A comparison of the properties of Sox-3 with Sry and 2 related genes: Sox-1 and Sox-2.</strong> Development 122: 509-520, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8625802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8625802</a>] [<a href="https://doi.org/10.1242/dev.122.2.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8625802">Collignon et al. (1996)</a> determined that the SOX3 gene has a single exon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8625802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<p>By use of a panel of somatic cell hybrids containing different terminal deletions of the long arm of the X chromosome, <a href="#16" class="mim-tip-reference" title="Stevanovic, M., Lovell-Badge, R., Collignon, J., Goodfellow, P. N. <strong>SOX3 is an X-linked gene related to SRY.</strong> Hum. Molec. Genet. 2: 2013-2018, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111369</a>] [<a href="https://doi.org/10.1093/hmg/2.12.2013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8111369">Stevanovic et al. (1993)</a> mapped the SOX3 gene to Xq26-q27. SOX3 appeared to map to a region of about 5 Mb between DXS51 and DXS98. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8111369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Foster, J. W., Graves, J. A. M. <strong>An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene.</strong> Proc. Nat. Acad. Sci. 91: 1927-1931, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8127908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8127908</a>] [<a href="https://doi.org/10.1073/pnas.91.5.1927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8127908">Foster and Graves (1994)</a> identified a sequence on the marsupial X chromosome that shares homology with SRY and shows near-identity with the mouse and human SOX3 gene (formerly called a3), the SOX gene most closely related to SRY. <a href="#5" class="mim-tip-reference" title="Foster, J. W., Graves, J. A. M. <strong>An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene.</strong> Proc. Nat. Acad. Sci. 91: 1927-1931, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8127908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8127908</a>] [<a href="https://doi.org/10.1073/pnas.91.5.1927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8127908">Foster and Graves (1994)</a> suggested that the highly conserved X chromosome-linked SOX3 represents the ancestral SOX gene from which the sex-determining SRY gene was derived. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8127908" 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 therian mammals (placentals and marsupials), sex is determined by an XX female:XY male system in which the SRY gene on the Y chromosome affects male determination. Birds have a ZW female:ZZ male system with no homology with mammalian sex chromosomes. In birds, dosage of a Z-borne gene, possibly Dmrt1 (<a href="/entry/602424">602424</a>), affects male determination. Platypus employ a sex-determining system of 5 X and 5 Y chromosomes. Females have 2 copies of the 5 Xs, and males have 5X and 5Y chromosomes, which form an alternating XY chain during male meiosis. <a href="#18" class="mim-tip-reference" title="Veyrunes, F., Waters, P. D., Miethke, P., Rens, W., McMillan, D., Alsop, A. E., Grutzner, F., Deakin, J. E., Whittington, C. M., Schatzkamer, K., Kremitzki, C. L., Graves, T., Ferguson-Smith, M. A., Warren, W., Graves, J. A. M. <strong>Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes.</strong> Genome Res. 18: 965-973, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gr.7101908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463302">Veyrunes et al. (2008)</a> found no homology between the 10 platypus sex chromosomes and the ancestral therian X chromosome, which is homologous to platypus chromosome 6. Orthologs of genes in the conserved region of human X (including SOX3, the gene from which SRY evolved) all map to platypus chromosome 6, which therefore represents the ancestral autosome from which the therian X and Y pair derived. The platypus X chromosomes have substantial homology with the bird Z chromosome (including DMRT1), and to segments syntenic with this region in the human genome. <a href="#18" class="mim-tip-reference" title="Veyrunes, F., Waters, P. D., Miethke, P., Rens, W., McMillan, D., Alsop, A. E., Grutzner, F., Deakin, J. E., Whittington, C. M., Schatzkamer, K., Kremitzki, C. L., Graves, T., Ferguson-Smith, M. A., Warren, W., Graves, J. A. M. <strong>Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes.</strong> Genome Res. 18: 965-973, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gr.7101908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463302">Veyrunes et al. (2008)</a> suggested that the therian X and Y chromosomes (including the SRY gene) evolved from an autosomal pair after the divergence of monotremes only 166 million years ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463302" 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 developing chick spinal cord, <a href="#3" class="mim-tip-reference" title="Bylund, M., Andersson, E., Novitch, B. G., Muhr, J. <strong>Vertebrate neurogenesis is counteracted by Sox1-3 activity.</strong> Nature Neurosci. 6: 1162-1168, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14517545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14517545</a>] [<a href="https://doi.org/10.1038/nn1131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14517545">Bylund et al. (2003)</a> found that Sox1, Sox2 (<a href="/entry/184429">184429</a>), and Sox3 were coexpressed in self-renewing progenitor cells and acted to inhibit neuronal differentiation. Active repression of the Sox genes promoted neural progenitor cells to initiate differentiation prematurely. Further studies showed that the ability of the proneural transcription factor neurogenin-2 (NEUROG2; <a href="/entry/606624">606624</a>) to promote neuronal differentiation was based on its ability to suppress Sox gene expression, thus showing that neurogenesis is regulated by an interplay between proneural proteins and inhibitory proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14517545" 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>On the basis of sequence homology, SOX3 is closely related to SOX1 (<a href="/entry/602148">602148</a>) and SOX2 (<a href="/entry/184429">184429</a>), and the products of all 3 genes belong to the SOXB1 subfamily and are expressed throughout the developing central nervous system (CNS) (<a href="#4" class="mim-tip-reference" title="Collignon, J., Sockanathan, S., Hacker, A., Cohen-Tannoudji, M., Norris, D., Rastan, S., Stevanovic, M., Goodfellow, P. N., Lovell-Badge, R. <strong>A comparison of the properties of Sox-3 with Sry and 2 related genes: Sox-1 and Sox-2.</strong> Development 122: 509-520, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8625802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8625802</a>] [<a href="https://doi.org/10.1242/dev.122.2.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8625802">Collignon et al., 1996</a>). All 3 proteins contain an HMG box. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8625802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Intellectual Developmental Disorder, X-linked, with Isolated Growth Hormone Deficiency</em></strong></p><p>
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In affected members of a family with mental retardation and isolated growth hormone deficiency (see <a href="/entry/300123">300123</a>) reported by <a href="#6" class="mim-tip-reference" title="Hamel, B. C. J., Smits, A. P. T., Otten, B. J., van den Helm, B., Ropers, H. H., Mariman, E. C. M. <strong>Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings.</strong> Am. J. Med. Genet. 64: 35-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826446</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826446">Hamel et al. (1996)</a>, <a href="#10" class="mim-tip-reference" title="Laumonnier, F., Ronce, N., Hamel, B. C. J., Thomas, P., Lespinasse, J., Raynaud, M., Paringaux, C., van Bokhoven, H., Kalscheuer, V., Fryns, J.-P., Chelly, J., Moraine, C., Briault, S. <strong>Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.</strong> Am. J. Hum. Genet. 71: 1450-1455, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12428212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12428212</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12428212[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/10.1086/344661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12428212">Laumonnier et al. (2002)</a> identified an in-frame duplication of 33 bp encoding 11 alanines in a polyalanine tract of the SOX3 gene (<a href="#0001">313430.0001</a>). The expression pattern during neural and pituitary development suggested that dysfunction of the SOX3 gene caused by the polyalanine expansion might disturb transcription pathways and the regulation of genes involved in cellular processes and functions required for cognitive and pituitary development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12428212+8826446" 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>Hypopituitarism, X-Linked</em></strong></p><p>
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<a href="#14" class="mim-tip-reference" title="Solomon, N. M., Ross, S. A., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L., Forrest, S. M., Thomas, P. Q. <strong>Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.</strong> J. Med. Genet. 41: 669-678, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342697</a>] [<a href="https://doi.org/10.1136/jmg.2003.016949" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15342697">Solomon et al. (2004)</a> determined that all cases of X-linked hypopituitarism from 5 unrelated families with Xq duplications contained duplications in the SOX3 gene, suggesting that increased dosage of SOX3 results in perturbation of pituitary and hypothalamic development. Three of the families had been reported by <a href="#9" class="mim-tip-reference" title="Lagerstrom-Fermer, M., Sundvall, M., Johnsen, E., Warne, G. L., Forrest, S. M., Zajac, J. D., Rickards, A., Ravine, D., Landegren, U., Pettersson, U. <strong>X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.</strong> Am. J. Hum. Genet. 60: 910-916, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106538</a>]" pmid="9106538">Lagerstrom-Fermer et al. (1997)</a>, <a href="#7" class="mim-tip-reference" title="Hol, F. A., Schepens, M. T., van Beersum, S. E. C., Redolfi, E., Affer, M., Vezzoni, P., Hamel, B. C. J., Karnes, P. S., Mariman, E. C. M., Zucchi, I. <strong>Identification and characterization of an Xq26-q27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes.</strong> Genomics 69: 174-181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11031100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11031100</a>] [<a href="https://doi.org/10.1006/geno.2000.6327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11031100">Hol et al. (2000)</a>, and <a href="#21" class="mim-tip-reference" title="Zipf, W. B., Kelch, R. P., Bacon, G. E. <strong>Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males.</strong> Clin. Genet. 11: 249-254, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/192503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">192503</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1977.tb01309.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="192503">Zipf et al. (1977)</a>. <a href="#13" class="mim-tip-reference" title="Solomon, N. M., Ross, S. A., Forrest, S. M., Thomas, P. Q., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L. <strong>Array comparative genomic hybridisation analysis of boys with X-linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. (Letter)</strong> J. Med. Genet. 44: e75, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400794</a>] [<a href="https://doi.org/10.1136/jmg.2007.049049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17400794">Solomon et al. (2007)</a> reported that they were unable to replicate the findings of an Xq26-q27 duplication in 3 families with X-linked hypopituitarism without mental retardation studied by <a href="#14" class="mim-tip-reference" title="Solomon, N. M., Ross, S. A., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L., Forrest, S. M., Thomas, P. Q. <strong>Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.</strong> J. Med. Genet. 41: 669-678, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342697</a>] [<a href="https://doi.org/10.1136/jmg.2003.016949" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15342697">Solomon et al. (2004)</a>, including the family reported by <a href="#21" class="mim-tip-reference" title="Zipf, W. B., Kelch, R. P., Bacon, G. E. <strong>Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males.</strong> Clin. Genet. 11: 249-254, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/192503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">192503</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1977.tb01309.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="192503">Zipf et al. (1977)</a>. The duplication was confirmed in the families with X-linked hypopituitarism and mental retardation (<a href="/entry/300123">300123</a>) reported by <a href="#9" class="mim-tip-reference" title="Lagerstrom-Fermer, M., Sundvall, M., Johnsen, E., Warne, G. L., Forrest, S. M., Zajac, J. D., Rickards, A., Ravine, D., Landegren, U., Pettersson, U. <strong>X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.</strong> Am. J. Hum. Genet. 60: 910-916, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106538</a>]" pmid="9106538">Lagerstrom-Fermer et al. (1997)</a> and <a href="#7" class="mim-tip-reference" title="Hol, F. A., Schepens, M. T., van Beersum, S. E. C., Redolfi, E., Affer, M., Vezzoni, P., Hamel, B. C. J., Karnes, P. S., Mariman, E. C. M., Zucchi, I. <strong>Identification and characterization of an Xq26-q27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes.</strong> Genomics 69: 174-181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11031100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11031100</a>] [<a href="https://doi.org/10.1006/geno.2000.6327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11031100">Hol et al. (2000)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11031100+9106538+17400794+192503+15342697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 unrelated families with X-linked panhypopituitarism (<a href="/entry/312000">312000</a>) and MRI evidence of structural pituitary abnormalities, including anterior pituitary hypoplasia, an ectopic posterior pituitary, and absent infundibulum, <a href="#20" class="mim-tip-reference" title="Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T. <strong>Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.</strong> Am. J. Hum. Genet. 76: 833-849, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15800844[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/10.1086/430134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800844">Woods et al. (2005)</a> identified duplications in the SOX3 gene (<a href="#0002">313430.0002</a> and <a href="#0003">313430.0003</a>, respectively). The findings implicated SOX3 in the development of the midline forebrain structures. None of the patients had mental retardation. The authors also identified a novel polymorphism, 127G-A (ala43 to thr), in a child from Ghana with sporadic combined pituitary hormone deficiency. This polymorphism was identified in heterozygous state in 3 of 19 normal controls from an Afro-Caribbean background. <a href="#20" class="mim-tip-reference" title="Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T. <strong>Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.</strong> Am. J. Hum. Genet. 76: 833-849, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15800844[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/10.1086/430134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800844">Woods et al. (2005)</a> concluded that both over- and underdosage of SOX3 are associated with variable panhypopituitarism, but not necessarily mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15800844" 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>46,XX Sex Reversal 3</em></strong></p><p>
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<a href="#17" class="mim-tip-reference" title="Sutton, E., Hughes, J., White, S., Sekido, R., Tan, J., Arboleda, V., Rogers, N., Knower, K., Rowley, L., Eyre, H., Rizzoti, K., McAninch, D., and 10 others. <strong>Identification of SOX3 as an XX male sex reversal gene in mice and humans.</strong> J. Clin. Invest. 121: 328-341, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21183788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21183788</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21183788[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI42580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21183788">Sutton et al. (2011)</a> screened a cohort of 16 SRY (<a href="/entry/480000">480000</a>)-negative 46,XX male patients (<a href="/entry/300833">300833</a>) for copy number variation (CNV) and identified rearrangements encompassing or in close proximity to the SOX3 gene in 3 patients. Patient 'A' had 2 microduplications of approximately 123 kb and 85 kb, with the larger spanning the entire SOX3 gene. FISH analysis was consistent with tandem duplication, and the centromeric duplication was approximately 70 kb downstream from the SOX3 gene, very close to a previously described deletion/insertion breakpoint in individuals with X-linked hypoparathyroidism (<a href="#2" class="mim-tip-reference" title="Bowl, M. R., Nesbit, M. A., Harding, B., Levy, E., Jefferson, A., Volpi, E., Rizzoti, K., Lovell-Badge, R., Schlessinger, D., Whyte, M. P., Thakker, R. V. <strong>An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism.</strong> J. Clin. Invest. 115: 2822-2831, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16167084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16167084</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16167084[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI24156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16167084">Bowl et al., 2005</a>), postulated to have a positional effect on SOX3 expression. Patient 'B' had a single 343-kb microdeletion immediately upstream of SOX3, suggesting that altered regulation rather than increased dosage of SOX3 is the cause of XX male sex reversal. Patient 'C,' who displayed a more complex phenotype including microcephaly, developmental delay, and growth retardation, had an approximately 6-Mb duplication that encompassed SOX3 and at least 18 additional distally located genes. The proximal breakpoint fell within the SOX3 regulatory region, close to the proximal SOX3 duplication breakpoint in the first patient. Transactivation assays using a human SOX9 (<a href="/entry/608160">608160</a>) testis enhancer sequence demonstrated approximately 10-fold and 5-fold activation by SOX3 and SRY, respectively, and activation levels were further enhanced in the presence of exogenous SF1 (NR5A1; <a href="/entry/184757">184757</a>), suggesting synergistic activation. <a href="#17" class="mim-tip-reference" title="Sutton, E., Hughes, J., White, S., Sekido, R., Tan, J., Arboleda, V., Rogers, N., Knower, K., Rowley, L., Eyre, H., Rizzoti, K., McAninch, D., and 10 others. <strong>Identification of SOX3 as an XX male sex reversal gene in mice and humans.</strong> J. Clin. Invest. 121: 328-341, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21183788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21183788</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21183788[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI42580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21183788">Sutton et al. (2011)</a> stated that these data, together with their studies in transgenic mice (see ANIMAL MODEL), suggested that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21183788+16167084" 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>Hypoparathyroidism, X-Linked</em></strong></p><p>
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In studies in the affected members of a Missouri family with X-linked hypoparathyroidism (HYPX; <a href="/entry/307700">307700</a>), originally reported by <a href="#11" class="mim-tip-reference" title="Peden, V. H. <strong>True idiopathic hypoparathyroidism as a sex-linked recessive trait.</strong> Am. J. Hum. Genet. 12: 323-337, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14431322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14431322</a>]" pmid="14431322">Peden (1960)</a>, <a href="#2" class="mim-tip-reference" title="Bowl, M. R., Nesbit, M. A., Harding, B., Levy, E., Jefferson, A., Volpi, E., Rizzoti, K., Lovell-Badge, R., Schlessinger, D., Whyte, M. P., Thakker, R. V. <strong>An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism.</strong> J. Clin. Invest. 115: 2822-2831, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16167084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16167084</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16167084[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI24156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16167084">Bowl et al. (2005)</a> undertook a detailed characterization of the genomic region containing the HYPX locus by combined analysis of single-nucleotide polymorphisms and sequence-tagged sites. This identified a 23- to 25-kb deletion, which did not contain genes. However, DNA fiber-FISH and pulsed-field gel electrophoresis revealed an approximately 340-kb insertion that replaced the deleted fragment. Use of flow-sorted X chromosome-specific libraries and DNA sequence analyses revealed that the telomeric and centromeric breakpoints on X were, respectively, approximately 67 kb downstream of SOX3 and within a repetitive sequence. Use of a monochromosomal somatic cell hybrid panel and metaphase-FISH mapping demonstrated that the insertion originated from 2p25 and contained a segment of the SNTG2 gene (<a href="/entry/608715">608715</a>) that lacked an open reading frame. However, the deletion-insertion, which represents a novel abnormality causing hypoparathyroidism, could result in a position effect on SOX3 expression. Indeed, Sox3 expression was demonstrated, by in situ hybridization, in the developing parathyroid tissue of mouse embryos between 10.5 and 15.5 days postcoitum. Thus, the results indicated a likely role for SOX3 in the embryonic development of the parathyroid glands. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14431322+16167084" 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="#15" class="mim-tip-reference" title="Stankiewicz, P., Thiele, H., Schlicker, M., Cseke-Friedrich, A., Bartel-Friedrich, S., Yatsenko, S. A., Lupski, J. R., Hansmann, I. <strong>Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia.</strong> Am. J. Med. Genet. 138A: 11-17, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16097007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16097007</a>] [<a href="https://doi.org/10.1002/ajmg.a.30910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16097007">Stankiewicz et al. (2005)</a> reported a family in which 4 women had short stature, speech defects with stuttering and dyslalia, and variable hearing impairment associated with a 7.5-Mb duplication of Xq26.2-q27.1 that encompassed or disrupted the SOX3 gene. A significant proportion of lymphocytes in 2 patients showed activation of the duplicated X chromosome. <a href="#15" class="mim-tip-reference" title="Stankiewicz, P., Thiele, H., Schlicker, M., Cseke-Friedrich, A., Bartel-Friedrich, S., Yatsenko, S. A., Lupski, J. R., Hansmann, I. <strong>Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia.</strong> Am. J. Med. Genet. 138A: 11-17, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16097007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16097007</a>] [<a href="https://doi.org/10.1002/ajmg.a.30910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16097007">Stankiewicz et al. (2005)</a> suggested that a dosage effect of SOX3 may be responsible for the speech disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16097007" 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="Bleyl, S. B., Byrne, J. L. B., South, S. T., Dries, D. C., Stevenson, D. A., Rope, A. F., Vianna-Morgante, A. M., Schoenwolf, G. C., Kivlin, J. D., Brothman, A., Carey, J. C. <strong>Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes.</strong> Am. J. Med. Genet. 143A: 2785-2795, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994562</a>] [<a href="https://doi.org/10.1002/ajmg.a.32036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994562">Bleyl et al. (2007)</a> reported a mother and son with anterior segment eye abnormalities and an unusual skeletal phenotype overlapping the SHOX (<a href="/entry/312865">312865</a>)-related skeletal dysplasias. The mother, who was previously described by <a href="#8" class="mim-tip-reference" title="Kivlin, J. D., Carey, J. C., Richey, M. A. <strong>Brachymesomelia and Peters anomaly: a new syndrome.</strong> Am. J. Med. Genet. 45: 416-419, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8465841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8465841</a>] [<a href="https://doi.org/10.1002/ajmg.1320450403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8465841">Kivlin et al. (1993)</a>, was found to have a 46,X,inv(X)(p22.3q27) pericentric inversion of the X chromosome; her son had a resultant 46,Y,rec(X)dup(Xq)inv(X)(p22.3q27) recombinant X chromosome. Array CGH mapping localized the Xq27.1 breakpoint to an interval approximately 90 kb 3-prime of the SOX3 gene; noting that no other genes lie within 350 kb, the authors suggested that misexpressed SOX3 may have led to the anterior chamber abnormalities in these patients. The Xp22.33 breakpoint was 30 to 68 kb 5-prime of the SHOX gene, which was presumably responsible for the skeletal phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17994562+8465841" 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="#19" class="mim-tip-reference" title="Weiss, J., Meeks, J. J., Hurley, L., Raverot, G., Frassetto, A., Jameson, J. L. <strong>Sox3 is required for gonadal function, but not sex determination, in males and females.</strong> Molec. Cell. Biol. 23: 8084-8091, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14585968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14585968[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/10.1128/MCB.23.22.8084-8091.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14585968">Weiss et al. (2003)</a> found that female Sox3-null mice developed ovaries but had excess follicular atresia, ovulation of defective oocytes, and severely reduced fertility. Pituitary and uterine functions were normal. Hemizygous male null mice developed testes but were hypogonadal. Testis weight was reduced, and there was extensive Sertoli cell vacuolization, loss of germ cells, reduced sperm counts, and disruption of the seminiferous tubules. Null mice of both sexes showed no overt behavioral deficits and normal growth hormone (<a href="/entry/139250">139250</a>) expression. Sox3-null mice consistently showed overgrowth and misalignment of the front teeth, and some mice had low body weight. <a href="#19" class="mim-tip-reference" title="Weiss, J., Meeks, J. J., Hurley, L., Raverot, G., Frassetto, A., Jameson, J. L. <strong>Sox3 is required for gonadal function, but not sex determination, in males and females.</strong> Molec. Cell. Biol. 23: 8084-8091, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14585968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14585968[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/10.1128/MCB.23.22.8084-8091.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14585968">Weiss et al. (2003)</a> concluded that Sox3 is not required for gonadal determination in mice, but is important for normal oocyte development and male testis differentiation and gametogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14585968" 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 embryos, <a href="#14" class="mim-tip-reference" title="Solomon, N. M., Ross, S. A., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L., Forrest, S. M., Thomas, P. Q. <strong>Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.</strong> J. Med. Genet. 41: 669-678, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342697</a>] [<a href="https://doi.org/10.1136/jmg.2003.016949" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15342697">Solomon et al. (2004)</a> demonstrated that the Sox3 gene was expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15342697" 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 pituitary develops from the interaction of the infundibulum, a region of the ventral diencephalon, and Rathke pouch, a derivative of oral ectoderm. Postnatally, its secretory functions are controlled by hypothalamic neurons, which also derive from the ventral diencephalon. To investigate the mechanism by which mutations in the single-exon gene SOX3 result in hypopituitarism and mental retardation, <a href="#12" class="mim-tip-reference" title="Rizzoti, K., Brunelli, S., Carmignac, D., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R. <strong>SOX3 is required during the formation of the hypothalamo-pituitary axis.</strong> Nature Genet. 36: 247-255, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14981518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14981518</a>] [<a href="https://doi.org/10.1038/ng1309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14981518">Rizzoti et al. (2004)</a> produced deletion of the Sox3 gene in mice and found that the deletion resulted in defects of pituitary function and of specific CNS midline structures. Cells in the ventral diencephalon, where Sox3 is usually highly expressed, had altered properties in mutant embryos, leading to abnormal development of the Rathke pouch, which does not express the gene. Pituitary and hypothalamic defects persisted postnatally, and SOX3 may also function in a subset of hypothalamic neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14981518" 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 to identify the genetic abnormality underlying X-linked recessive hypoparathyroidism (<a href="/entry/307700">307700</a>), <a href="#2" class="mim-tip-reference" title="Bowl, M. R., Nesbit, M. A., Harding, B., Levy, E., Jefferson, A., Volpi, E., Rizzoti, K., Lovell-Badge, R., Schlessinger, D., Whyte, M. P., Thakker, R. V. <strong>An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism.</strong> J. Clin. Invest. 115: 2822-2831, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16167084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16167084</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16167084[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI24156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16167084">Bowl et al. (2005)</a> examined Sox3 expression in mouse embryos by in situ hybridization. They demonstrated expression in the developing parathyroid tissue of mouse embryos between 10.5 and 15.5 days postcoitum. Thus, the results indicated a likely role for SOX3 in the embryonic development of the parathyroid glands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16167084" 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="Sutton, E., Hughes, J., White, S., Sekido, R., Tan, J., Arboleda, V., Rogers, N., Knower, K., Rowley, L., Eyre, H., Rizzoti, K., McAninch, D., and 10 others. <strong>Identification of SOX3 as an XX male sex reversal gene in mice and humans.</strong> J. Clin. Invest. 121: 328-341, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21183788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21183788</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21183788[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI42580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21183788">Sutton et al. (2011)</a> generated and characterized transgenic mice overexpressing Sox3. They showed that ectopic expression of Sox3 in uncommitted XX gonads was sufficient to divert the program of ovarian development toward testis formation, leading to XX males. Further analysis revealed that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a mechanism similar to that of Sry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21183788" 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 affected members of a family with X-linked intellectual developmental disorder and isolated growth hormone deficiency (see <a href="/entry/300123">300123</a>) reported by <a href="#6" class="mim-tip-reference" title="Hamel, B. C. J., Smits, A. P. T., Otten, B. J., van den Helm, B., Ropers, H. H., Mariman, E. C. M. <strong>Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings.</strong> Am. J. Med. Genet. 64: 35-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826446</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826446">Hamel et al. (1996)</a>, <a href="#10" class="mim-tip-reference" title="Laumonnier, F., Ronce, N., Hamel, B. C. J., Thomas, P., Lespinasse, J., Raynaud, M., Paringaux, C., van Bokhoven, H., Kalscheuer, V., Fryns, J.-P., Chelly, J., Moraine, C., Briault, S. <strong>Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.</strong> Am. J. Hum. Genet. 71: 1450-1455, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12428212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12428212</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12428212[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/10.1086/344661" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12428212">Laumonnier et al. (2002)</a> identified a 33-bp duplication (711-743dup) in the SOX3 gene. The duplication codes for 11 alanines in a polyalanine tract, predicted to cause expansion of the normal polyalanine tract (amino acids 234-249) by 15 to 26 alanine residues. The family had been described clinically by <a href="#6" class="mim-tip-reference" title="Hamel, B. C. J., Smits, A. P. T., Otten, B. J., van den Helm, B., Ropers, H. H., Mariman, E. C. M. <strong>Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings.</strong> Am. J. Med. Genet. 64: 35-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826446</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826446">Hamel et al. (1996)</a>. Clinical examination revealed facial anomalies in some, but not all, of the patients. On average, untreated patients reached their final height, ranging from 135 to 159 cm, at the age of 24 or 25 years. In all patients examined, behavior was considered infantile, and laboratory investigations demonstrated total growth hormone deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12428212+8826446" 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 2 male maternal half sibs with X-linked panhypopituitarism (<a href="/entry/312000">312000</a>), <a href="#20" class="mim-tip-reference" title="Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T. <strong>Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.</strong> Am. J. Hum. Genet. 76: 833-849, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15800844[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/10.1086/430134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800844">Woods et al. (2005)</a> identified a submicroscopic duplication of Xq27.1 (685.6 kb) containing the SOX3 gene. Brain MRI showed anterior pituitary hypoplasia, ectopic posterior pituitary, and absent infundibulum. Mental retardation was not present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15800844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 PANHYPOPITUITARISM, X-LINKED</strong>
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SOX3, 21-BP DUP, NT720, ALANINE TRACT EXPANSION
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010545" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010545" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010545</a>
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<p>In 4 brothers, born of a consanguineous Qatari couple, with X-linked panhypopituitarism (<a href="/entry/312000">312000</a>), <a href="#20" class="mim-tip-reference" title="Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T. <strong>Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.</strong> Am. J. Hum. Genet. 76: 833-849, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15800844[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/10.1086/430134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800844">Woods et al. (2005)</a> identified a 21-bp duplication between nucleotides 720 and 721 of the SOX3 gene. The duplication resulted in an in-frame addition of 7 alanine residues within a polyalanine tract (Ala(7)240ins241). The sibs had absent infundibulum, severe anterior pituitary hypoplasia, and ectopic posterior pituitary. There was no associated mental retardation. The mother of all 4 children, who was heterozygous for this mutation, did not exhibit significantly skewed X inactivation in DNA extracted from blood. In vitro functional expression studies indicated that the expansion was associated with decreased SOX3 activity and impaired nuclear localization of the mutant protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15800844" 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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<strong>Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes.</strong>
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[<a href="https://doi.org/10.1002/ajmg.a.32036" target="_blank">Full Text</a>]
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Bowl, M. R., Nesbit, M. A., Harding, B., Levy, E., Jefferson, A., Volpi, E., Rizzoti, K., Lovell-Badge, R., Schlessinger, D., Whyte, M. P., Thakker, R. V.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16167084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16167084</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16167084[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=16167084" 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/10.1172/JCI24156" target="_blank">Full Text</a>]
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Bylund, M., Andersson, E., Novitch, B. G., Muhr, J.
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[<a href="https://doi.org/10.1038/nn1131" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1242/dev.122.2.509" target="_blank">Full Text</a>]
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Foster, J. W., Graves, J. A. M.
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<strong>An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene.</strong>
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Proc. Nat. Acad. Sci. 91: 1927-1931, 1994.
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[<a href="https://doi.org/10.1073/pnas.91.5.1927" target="_blank">Full Text</a>]
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Hamel, B. C. J., Smits, A. P. T., Otten, B. J., van den Helm, B., Ropers, H. H., Mariman, E. C. M.
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[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q" target="_blank">Full Text</a>]
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Hol, F. A., Schepens, M. T., van Beersum, S. E. C., Redolfi, E., Affer, M., Vezzoni, P., Hamel, B. C. J., Karnes, P. S., Mariman, E. C. M., Zucchi, I.
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[<a href="https://doi.org/10.1006/geno.2000.6327" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320450403" target="_blank">Full Text</a>]
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<a id="Laumonnier2002" class="mim-anchor"></a>
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Laumonnier, F., Ronce, N., Hamel, B. C. J., Thomas, P., Lespinasse, J., Raynaud, M., Paringaux, C., van Bokhoven, H., Kalscheuer, V., Fryns, J.-P., Chelly, J., Moraine, C., Briault, S.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12428212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12428212</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12428212[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=12428212" 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/10.1086/344661" target="_blank">Full Text</a>]
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Rizzoti, K., Brunelli, S., Carmignac, D., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R.
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<strong>SOX3 is required during the formation of the hypothalamo-pituitary axis.</strong>
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Nature Genet. 36: 247-255, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14981518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14981518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14981518" 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/ng1309" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Solomon2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Solomon, N. M., Ross, S. A., Forrest, S. M., Thomas, P. Q., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L.
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<strong>Array comparative genomic hybridisation analysis of boys with X-linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. (Letter)</strong>
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J. Med. Genet. 44: e75, 2007. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400794</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17400794" 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/jmg.2007.049049" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Solomon2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Solomon, N. M., Ross, S. A., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L., Forrest, S. M., Thomas, P. Q.
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<strong>Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.</strong>
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J. Med. Genet. 41: 669-678, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15342697" 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/jmg.2003.016949" target="_blank">Full Text</a>]
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<a id="15" class="mim-anchor"></a>
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<a id="Stankiewicz2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stankiewicz, P., Thiele, H., Schlicker, M., Cseke-Friedrich, A., Bartel-Friedrich, S., Yatsenko, S. A., Lupski, J. R., Hansmann, I.
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<strong>Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia.</strong>
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Am. J. Med. Genet. 138A: 11-17, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16097007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16097007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16097007" 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/ajmg.a.30910" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Stevanovic1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stevanovic, M., Lovell-Badge, R., Collignon, J., Goodfellow, P. N.
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<strong>SOX3 is an X-linked gene related to SRY.</strong>
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Hum. Molec. Genet. 2: 2013-2018, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8111369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/2.12.2013" target="_blank">Full Text</a>]
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<a id="17" class="mim-anchor"></a>
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<a id="Sutton2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sutton, E., Hughes, J., White, S., Sekido, R., Tan, J., Arboleda, V., Rogers, N., Knower, K., Rowley, L., Eyre, H., Rizzoti, K., McAninch, D., and 10 others.
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<strong>Identification of SOX3 as an XX male sex reversal gene in mice and humans.</strong>
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J. Clin. Invest. 121: 328-341, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21183788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21183788</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21183788[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=21183788" 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/10.1172/JCI42580" target="_blank">Full Text</a>]
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<a id="18" class="mim-anchor"></a>
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<a id="Veyrunes2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Veyrunes, F., Waters, P. D., Miethke, P., Rens, W., McMillan, D., Alsop, A. E., Grutzner, F., Deakin, J. E., Whittington, C. M., Schatzkamer, K., Kremitzki, C. L., Graves, T., Ferguson-Smith, M. A., Warren, W., Graves, J. A. M.
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<strong>Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes.</strong>
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Genome Res. 18: 965-973, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463302[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=18463302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gr.7101908" target="_blank">Full Text</a>]
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Weiss2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weiss, J., Meeks, J. J., Hurley, L., Raverot, G., Frassetto, A., Jameson, J. L.
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<strong>Sox3 is required for gonadal function, but not sex determination, in males and females.</strong>
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Molec. Cell. Biol. 23: 8084-8091, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14585968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14585968[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=14585968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/MCB.23.22.8084-8091.2003" target="_blank">Full Text</a>]
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<a id="20" class="mim-anchor"></a>
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<a id="Woods2005" class="mim-anchor"></a>
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Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T.
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<strong>Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.</strong>
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Am. J. Hum. Genet. 76: 833-849, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15800844[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=15800844" 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/10.1086/430134" target="_blank">Full Text</a>]
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<a id="21" class="mim-anchor"></a>
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<a id="Zipf1977" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zipf, W. B., Kelch, R. P., Bacon, G. E.
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<strong>Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males.</strong>
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Clin. Genet. 11: 249-254, 1977.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/192503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">192503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=192503" 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/10.1111/j.1399-0004.1977.tb01309.x" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 1/24/2011
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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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Patricia A. Hartz - updated : 9/21/2009<br>Marla J. F. O'Neill - updated : 4/28/2008<br>Anne M. Stumpf - updated : 11/10/2005<br>Victor A. McKusick - updated : 11/4/2005<br>Cassandra L. Kniffin - updated : 9/19/2005<br>Victor A. McKusick - updated : 4/13/2005<br>Victor A. McKusick - updated : 10/12/2004<br>Patricia A. Hartz - updated : 8/9/2004<br>Victor A. McKusick - updated : 2/23/2004<br>Cassandra L. Kniffin - updated : 10/3/2003<br>Victor A. McKusick - updated : 1/8/2003
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 5/23/1994
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 02/19/2025
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carol : 04/11/2023<br>carol : 08/20/2021<br>carol : 11/08/2019<br>carol : 02/06/2019<br>carol : 04/26/2011<br>wwang : 2/15/2011<br>terry : 1/24/2011<br>carol : 9/22/2009<br>terry : 9/21/2009<br>wwang : 6/12/2008<br>carol : 5/2/2008<br>ckniffin : 5/1/2008<br>wwang : 4/28/2008<br>alopez : 11/10/2005<br>alopez : 11/10/2005<br>terry : 11/4/2005<br>wwang : 10/31/2005<br>wwang : 9/30/2005<br>ckniffin : 9/19/2005<br>tkritzer : 4/15/2005<br>alopez : 4/13/2005<br>terry : 4/13/2005<br>terry : 4/4/2005<br>tkritzer : 10/14/2004<br>terry : 10/12/2004<br>mgross : 8/11/2004<br>terry : 8/9/2004<br>tkritzer : 2/23/2004<br>terry : 2/23/2004<br>alopez : 10/31/2003<br>carol : 10/3/2003<br>ckniffin : 10/3/2003<br>cwells : 1/13/2003<br>terry : 1/8/2003<br>terry : 5/20/1999<br>dkim : 12/4/1998<br>mark : 12/5/1997<br>mark : 6/25/1996<br>carol : 5/23/1994
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<strong>*</strong> 313430
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<h3>
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SRY-BOX 3; SOX3
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<em>Alternative titles; symbols</em>
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<h4>
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SRY-RELATED HMG-BOX GENE 3
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<strong><em>HGNC Approved Gene Symbol: SOX3</em></strong>
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<strong>SNOMEDCT:</strong> 237683004;
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<strong>
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<em>
|
|
Cytogenetic location: Xq27.1
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Genomic coordinates <span class="small">(GRCh38)</span> : X:140,502,985-140,505,069 </span>
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</em>
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</strong>
|
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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|
</div>
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<div>
|
|
<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">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
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|
</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
|
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<th>
|
|
Inheritance
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</th>
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<th>
|
|
Phenotype <br /> mapping key
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|
</th>
|
|
</tr>
|
|
</thead>
|
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<tbody>
|
|
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|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
Xq27.1
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|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Intellectual developmental disorder, X-linked, with isolated growth hormone deficiency
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
300123
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|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
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|
|
|
|
|
|
|
|
|
</tr>
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Panhypopituitarism, X-linked
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
312000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
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|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<span class="mim-text-font">
|
|
<p>The mammalian genome contains a family of genes that are related to SRY (480000), the testis-determining gene. The homology is restricted to the region of SRY that encodes a DNA-binding motif of the HMG-box class (the DNA-binding domain is called HMG for 'high mobility group'). These genes have been named SOX, for SRY-related HMG-box (see SOX1; 602148).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
<span class="mim-text-font">
|
|
<p>Stevanovic et al. (1993) cloned and characterized SOX3. A reverse transcription coupled with PCR (RT-PCR) was used to amplify SRY-related transcripts expressed during embryogenesis in human fetal spinal cord. Inspection of fragments detected by one of them showed a difference between males and females, suggesting a SOX gene located on the X chromosome. Isolation and sequencing of the gene showed 97.2% similarity to the protein encoded by the mouse Sox3 gene which is also located on the X chromosome. The RACE (rapid amplification of complementary DNA ends) method was used to define the 3-prime end of the transcript and to confirm that the SOX3 gene is expressed. Using the sensitive RT-PCR assay, SOX3 gene transcripts were detected in several fetal tissues. </p>
|
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</span>
|
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<div>
|
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<br />
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</div>
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<div>
|
|
<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
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</span>
|
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</h4>
|
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</div>
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|
|
|
|
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|
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<span class="mim-text-font">
|
|
<p>Collignon et al. (1996) determined that the SOX3 gene has a single exon. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
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</div>
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<div>
|
|
<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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|
|
<span class="mim-text-font">
|
|
<p>By use of a panel of somatic cell hybrids containing different terminal deletions of the long arm of the X chromosome, Stevanovic et al. (1993) mapped the SOX3 gene to Xq26-q27. SOX3 appeared to map to a region of about 5 Mb between DXS51 and DXS98. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Evolution</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
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<span class="mim-text-font">
|
|
<p>Foster and Graves (1994) identified a sequence on the marsupial X chromosome that shares homology with SRY and shows near-identity with the mouse and human SOX3 gene (formerly called a3), the SOX gene most closely related to SRY. Foster and Graves (1994) suggested that the highly conserved X chromosome-linked SOX3 represents the ancestral SOX gene from which the sex-determining SRY gene was derived. </p><p>In therian mammals (placentals and marsupials), sex is determined by an XX female:XY male system in which the SRY gene on the Y chromosome affects male determination. Birds have a ZW female:ZZ male system with no homology with mammalian sex chromosomes. In birds, dosage of a Z-borne gene, possibly Dmrt1 (602424), affects male determination. Platypus employ a sex-determining system of 5 X and 5 Y chromosomes. Females have 2 copies of the 5 Xs, and males have 5X and 5Y chromosomes, which form an alternating XY chain during male meiosis. Veyrunes et al. (2008) found no homology between the 10 platypus sex chromosomes and the ancestral therian X chromosome, which is homologous to platypus chromosome 6. Orthologs of genes in the conserved region of human X (including SOX3, the gene from which SRY evolved) all map to platypus chromosome 6, which therefore represents the ancestral autosome from which the therian X and Y pair derived. The platypus X chromosomes have substantial homology with the bird Z chromosome (including DMRT1), and to segments syntenic with this region in the human genome. Veyrunes et al. (2008) suggested that the therian X and Y chromosomes (including the SRY gene) evolved from an autosomal pair after the divergence of monotremes only 166 million years ago. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In developing chick spinal cord, Bylund et al. (2003) found that Sox1, Sox2 (184429), and Sox3 were coexpressed in self-renewing progenitor cells and acted to inhibit neuronal differentiation. Active repression of the Sox genes promoted neural progenitor cells to initiate differentiation prematurely. Further studies showed that the ability of the proneural transcription factor neurogenin-2 (NEUROG2; 606624) to promote neuronal differentiation was based on its ability to suppress Sox gene expression, thus showing that neurogenesis is regulated by an interplay between proneural proteins and inhibitory proteins. </p><p>On the basis of sequence homology, SOX3 is closely related to SOX1 (602148) and SOX2 (184429), and the products of all 3 genes belong to the SOXB1 subfamily and are expressed throughout the developing central nervous system (CNS) (Collignon et al., 1996). All 3 proteins contain an HMG box. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Intellectual Developmental Disorder, X-linked, with Isolated Growth Hormone Deficiency</em></strong></p><p>
|
|
In affected members of a family with mental retardation and isolated growth hormone deficiency (see 300123) reported by Hamel et al. (1996), Laumonnier et al. (2002) identified an in-frame duplication of 33 bp encoding 11 alanines in a polyalanine tract of the SOX3 gene (313430.0001). The expression pattern during neural and pituitary development suggested that dysfunction of the SOX3 gene caused by the polyalanine expansion might disturb transcription pathways and the regulation of genes involved in cellular processes and functions required for cognitive and pituitary development. </p><p><strong><em>Hypopituitarism, X-Linked</em></strong></p><p>
|
|
Solomon et al. (2004) determined that all cases of X-linked hypopituitarism from 5 unrelated families with Xq duplications contained duplications in the SOX3 gene, suggesting that increased dosage of SOX3 results in perturbation of pituitary and hypothalamic development. Three of the families had been reported by Lagerstrom-Fermer et al. (1997), Hol et al. (2000), and Zipf et al. (1977). Solomon et al. (2007) reported that they were unable to replicate the findings of an Xq26-q27 duplication in 3 families with X-linked hypopituitarism without mental retardation studied by Solomon et al. (2004), including the family reported by Zipf et al. (1977). The duplication was confirmed in the families with X-linked hypopituitarism and mental retardation (300123) reported by Lagerstrom-Fermer et al. (1997) and Hol et al. (2000). </p><p>In affected members of 2 unrelated families with X-linked panhypopituitarism (312000) and MRI evidence of structural pituitary abnormalities, including anterior pituitary hypoplasia, an ectopic posterior pituitary, and absent infundibulum, Woods et al. (2005) identified duplications in the SOX3 gene (313430.0002 and 313430.0003, respectively). The findings implicated SOX3 in the development of the midline forebrain structures. None of the patients had mental retardation. The authors also identified a novel polymorphism, 127G-A (ala43 to thr), in a child from Ghana with sporadic combined pituitary hormone deficiency. This polymorphism was identified in heterozygous state in 3 of 19 normal controls from an Afro-Caribbean background. Woods et al. (2005) concluded that both over- and underdosage of SOX3 are associated with variable panhypopituitarism, but not necessarily mental retardation. </p><p><strong><em>46,XX Sex Reversal 3</em></strong></p><p>
|
|
Sutton et al. (2011) screened a cohort of 16 SRY (480000)-negative 46,XX male patients (300833) for copy number variation (CNV) and identified rearrangements encompassing or in close proximity to the SOX3 gene in 3 patients. Patient 'A' had 2 microduplications of approximately 123 kb and 85 kb, with the larger spanning the entire SOX3 gene. FISH analysis was consistent with tandem duplication, and the centromeric duplication was approximately 70 kb downstream from the SOX3 gene, very close to a previously described deletion/insertion breakpoint in individuals with X-linked hypoparathyroidism (Bowl et al., 2005), postulated to have a positional effect on SOX3 expression. Patient 'B' had a single 343-kb microdeletion immediately upstream of SOX3, suggesting that altered regulation rather than increased dosage of SOX3 is the cause of XX male sex reversal. Patient 'C,' who displayed a more complex phenotype including microcephaly, developmental delay, and growth retardation, had an approximately 6-Mb duplication that encompassed SOX3 and at least 18 additional distally located genes. The proximal breakpoint fell within the SOX3 regulatory region, close to the proximal SOX3 duplication breakpoint in the first patient. Transactivation assays using a human SOX9 (608160) testis enhancer sequence demonstrated approximately 10-fold and 5-fold activation by SOX3 and SRY, respectively, and activation levels were further enhanced in the presence of exogenous SF1 (NR5A1; 184757), suggesting synergistic activation. Sutton et al. (2011) stated that these data, together with their studies in transgenic mice (see ANIMAL MODEL), suggested that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad. </p><p><strong><em>Hypoparathyroidism, X-Linked</em></strong></p><p>
|
|
In studies in the affected members of a Missouri family with X-linked hypoparathyroidism (HYPX; 307700), originally reported by Peden (1960), Bowl et al. (2005) undertook a detailed characterization of the genomic region containing the HYPX locus by combined analysis of single-nucleotide polymorphisms and sequence-tagged sites. This identified a 23- to 25-kb deletion, which did not contain genes. However, DNA fiber-FISH and pulsed-field gel electrophoresis revealed an approximately 340-kb insertion that replaced the deleted fragment. Use of flow-sorted X chromosome-specific libraries and DNA sequence analyses revealed that the telomeric and centromeric breakpoints on X were, respectively, approximately 67 kb downstream of SOX3 and within a repetitive sequence. Use of a monochromosomal somatic cell hybrid panel and metaphase-FISH mapping demonstrated that the insertion originated from 2p25 and contained a segment of the SNTG2 gene (608715) that lacked an open reading frame. However, the deletion-insertion, which represents a novel abnormality causing hypoparathyroidism, could result in a position effect on SOX3 expression. Indeed, Sox3 expression was demonstrated, by in situ hybridization, in the developing parathyroid tissue of mouse embryos between 10.5 and 15.5 days postcoitum. Thus, the results indicated a likely role for SOX3 in the embryonic development of the parathyroid glands. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Stankiewicz et al. (2005) reported a family in which 4 women had short stature, speech defects with stuttering and dyslalia, and variable hearing impairment associated with a 7.5-Mb duplication of Xq26.2-q27.1 that encompassed or disrupted the SOX3 gene. A significant proportion of lymphocytes in 2 patients showed activation of the duplicated X chromosome. Stankiewicz et al. (2005) suggested that a dosage effect of SOX3 may be responsible for the speech disorder. </p><p>Bleyl et al. (2007) reported a mother and son with anterior segment eye abnormalities and an unusual skeletal phenotype overlapping the SHOX (312865)-related skeletal dysplasias. The mother, who was previously described by Kivlin et al. (1993), was found to have a 46,X,inv(X)(p22.3q27) pericentric inversion of the X chromosome; her son had a resultant 46,Y,rec(X)dup(Xq)inv(X)(p22.3q27) recombinant X chromosome. Array CGH mapping localized the Xq27.1 breakpoint to an interval approximately 90 kb 3-prime of the SOX3 gene; noting that no other genes lie within 350 kb, the authors suggested that misexpressed SOX3 may have led to the anterior chamber abnormalities in these patients. The Xp22.33 breakpoint was 30 to 68 kb 5-prime of the SHOX gene, which was presumably responsible for the skeletal phenotype. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Weiss et al. (2003) found that female Sox3-null mice developed ovaries but had excess follicular atresia, ovulation of defective oocytes, and severely reduced fertility. Pituitary and uterine functions were normal. Hemizygous male null mice developed testes but were hypogonadal. Testis weight was reduced, and there was extensive Sertoli cell vacuolization, loss of germ cells, reduced sperm counts, and disruption of the seminiferous tubules. Null mice of both sexes showed no overt behavioral deficits and normal growth hormone (139250) expression. Sox3-null mice consistently showed overgrowth and misalignment of the front teeth, and some mice had low body weight. Weiss et al. (2003) concluded that Sox3 is not required for gonadal determination in mice, but is important for normal oocyte development and male testis differentiation and gametogenesis. </p><p>In mouse embryos, Solomon et al. (2004) demonstrated that the Sox3 gene was expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. </p><p>The pituitary develops from the interaction of the infundibulum, a region of the ventral diencephalon, and Rathke pouch, a derivative of oral ectoderm. Postnatally, its secretory functions are controlled by hypothalamic neurons, which also derive from the ventral diencephalon. To investigate the mechanism by which mutations in the single-exon gene SOX3 result in hypopituitarism and mental retardation, Rizzoti et al. (2004) produced deletion of the Sox3 gene in mice and found that the deletion resulted in defects of pituitary function and of specific CNS midline structures. Cells in the ventral diencephalon, where Sox3 is usually highly expressed, had altered properties in mutant embryos, leading to abnormal development of the Rathke pouch, which does not express the gene. Pituitary and hypothalamic defects persisted postnatally, and SOX3 may also function in a subset of hypothalamic neurons. </p><p>In studies to identify the genetic abnormality underlying X-linked recessive hypoparathyroidism (307700), Bowl et al. (2005) examined Sox3 expression in mouse embryos by in situ hybridization. They demonstrated expression in the developing parathyroid tissue of mouse embryos between 10.5 and 15.5 days postcoitum. Thus, the results indicated a likely role for SOX3 in the embryonic development of the parathyroid glands. </p><p>Sutton et al. (2011) generated and characterized transgenic mice overexpressing Sox3. They showed that ectopic expression of Sox3 in uncommitted XX gonads was sufficient to divert the program of ovarian development toward testis formation, leading to XX males. Further analysis revealed that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a mechanism similar to that of Sry. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>3 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, WITH ISOLATED GROWTH HORMONE DEFICIENCY</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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SOX3, 33-BP DUP, NT711-743, ALANINE TRACT EXPANSION
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<br />
|
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|
|
ClinVar: RCV000010543
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|
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</span>
|
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</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with X-linked intellectual developmental disorder and isolated growth hormone deficiency (see 300123) reported by Hamel et al. (1996), Laumonnier et al. (2002) identified a 33-bp duplication (711-743dup) in the SOX3 gene. The duplication codes for 11 alanines in a polyalanine tract, predicted to cause expansion of the normal polyalanine tract (amino acids 234-249) by 15 to 26 alanine residues. The family had been described clinically by Hamel et al. (1996). Clinical examination revealed facial anomalies in some, but not all, of the patients. On average, untreated patients reached their final height, ranging from 135 to 159 cm, at the age of 24 or 25 years. In all patients examined, behavior was considered infantile, and laboratory investigations demonstrated total growth hormone deficiency. </p>
|
|
</span>
|
|
</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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PANHYPOPITUITARISM, X-LINKED</strong>
|
|
</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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|
|
SOX3, DUP
|
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<br />
|
|
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|
|
ClinVar: RCV000010544
|
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|
|
</span>
|
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</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 male maternal half sibs with X-linked panhypopituitarism (312000), Woods et al. (2005) identified a submicroscopic duplication of Xq27.1 (685.6 kb) containing the SOX3 gene. Brain MRI showed anterior pituitary hypoplasia, ectopic posterior pituitary, and absent infundibulum. Mental retardation was not present. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PANHYPOPITUITARISM, X-LINKED</strong>
|
|
</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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|
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SOX3, 21-BP DUP, NT720, ALANINE TRACT EXPANSION
|
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<br />
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|
|
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ClinVar: RCV000010545
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<p>In 4 brothers, born of a consanguineous Qatari couple, with X-linked panhypopituitarism (312000), Woods et al. (2005) identified a 21-bp duplication between nucleotides 720 and 721 of the SOX3 gene. The duplication resulted in an in-frame addition of 7 alanine residues within a polyalanine tract (Ala(7)240ins241). The sibs had absent infundibulum, severe anterior pituitary hypoplasia, and ectopic posterior pituitary. There was no associated mental retardation. The mother of all 4 children, who was heterozygous for this mutation, did not exhibit significantly skewed X inactivation in DNA extracted from blood. In vitro functional expression studies indicated that the expansion was associated with decreased SOX3 activity and impaired nuclear localization of the mutant protein. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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Bleyl, S. B., Byrne, J. L. B., South, S. T., Dries, D. C., Stevenson, D. A., Rope, A. F., Vianna-Morgante, A. M., Schoenwolf, G. C., Kivlin, J. D., Brothman, A., Carey, J. C.
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<strong>Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes.</strong>
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Am. J. Med. Genet. 143A: 2785-2795, 2007.
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[PubMed: 17994562]
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[Full Text: https://doi.org/10.1002/ajmg.a.32036]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bowl, M. R., Nesbit, M. A., Harding, B., Levy, E., Jefferson, A., Volpi, E., Rizzoti, K., Lovell-Badge, R., Schlessinger, D., Whyte, M. P., Thakker, R. V.
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<strong>An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism.</strong>
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J. Clin. Invest. 115: 2822-2831, 2005.
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[PubMed: 16167084]
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[Full Text: https://doi.org/10.1172/JCI24156]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bylund, M., Andersson, E., Novitch, B. G., Muhr, J.
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<strong>Vertebrate neurogenesis is counteracted by Sox1-3 activity.</strong>
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Nature Neurosci. 6: 1162-1168, 2003.
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[PubMed: 14517545]
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[Full Text: https://doi.org/10.1038/nn1131]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Collignon, J., Sockanathan, S., Hacker, A., Cohen-Tannoudji, M., Norris, D., Rastan, S., Stevanovic, M., Goodfellow, P. N., Lovell-Badge, R.
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<strong>A comparison of the properties of Sox-3 with Sry and 2 related genes: Sox-1 and Sox-2.</strong>
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Development 122: 509-520, 1996.
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[PubMed: 8625802]
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[Full Text: https://doi.org/10.1242/dev.122.2.509]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Foster, J. W., Graves, J. A. M.
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<strong>An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene.</strong>
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Proc. Nat. Acad. Sci. 91: 1927-1931, 1994.
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[PubMed: 8127908]
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[Full Text: https://doi.org/10.1073/pnas.91.5.1927]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hamel, B. C. J., Smits, A. P. T., Otten, B. J., van den Helm, B., Ropers, H. H., Mariman, E. C. M.
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<strong>Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings.</strong>
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Am. J. Med. Genet. 64: 35-41, 1996.
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[PubMed: 8826446]
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[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hol, F. A., Schepens, M. T., van Beersum, S. E. C., Redolfi, E., Affer, M., Vezzoni, P., Hamel, B. C. J., Karnes, P. S., Mariman, E. C. M., Zucchi, I.
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<strong>Identification and characterization of an Xq26-q27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes.</strong>
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Genomics 69: 174-181, 2000.
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[PubMed: 11031100]
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[Full Text: https://doi.org/10.1006/geno.2000.6327]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kivlin, J. D., Carey, J. C., Richey, M. A.
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<strong>Brachymesomelia and Peters anomaly: a new syndrome.</strong>
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Am. J. Med. Genet. 45: 416-419, 1993.
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[PubMed: 8465841]
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[Full Text: https://doi.org/10.1002/ajmg.1320450403]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lagerstrom-Fermer, M., Sundvall, M., Johnsen, E., Warne, G. L., Forrest, S. M., Zajac, J. D., Rickards, A., Ravine, D., Landegren, U., Pettersson, U.
|
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<strong>X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.</strong>
|
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Am. J. Hum. Genet. 60: 910-916, 1997.
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[PubMed: 9106538]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Laumonnier, F., Ronce, N., Hamel, B. C. J., Thomas, P., Lespinasse, J., Raynaud, M., Paringaux, C., van Bokhoven, H., Kalscheuer, V., Fryns, J.-P., Chelly, J., Moraine, C., Briault, S.
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<strong>Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.</strong>
|
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Am. J. Hum. Genet. 71: 1450-1455, 2002.
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[PubMed: 12428212]
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[Full Text: https://doi.org/10.1086/344661]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Peden, V. H.
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<strong>True idiopathic hypoparathyroidism as a sex-linked recessive trait.</strong>
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Am. J. Hum. Genet. 12: 323-337, 1960.
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[PubMed: 14431322]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Rizzoti, K., Brunelli, S., Carmignac, D., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R.
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<strong>SOX3 is required during the formation of the hypothalamo-pituitary axis.</strong>
|
|
Nature Genet. 36: 247-255, 2004.
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[PubMed: 14981518]
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[Full Text: https://doi.org/10.1038/ng1309]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Solomon, N. M., Ross, S. A., Forrest, S. M., Thomas, P. Q., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L.
|
|
<strong>Array comparative genomic hybridisation analysis of boys with X-linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. (Letter)</strong>
|
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J. Med. Genet. 44: e75, 2007. Note: Electronic Article.
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[PubMed: 17400794]
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[Full Text: https://doi.org/10.1136/jmg.2007.049049]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Solomon, N. M., Ross, S. A., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L., Forrest, S. M., Thomas, P. Q.
|
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<strong>Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.</strong>
|
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J. Med. Genet. 41: 669-678, 2004.
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[PubMed: 15342697]
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[Full Text: https://doi.org/10.1136/jmg.2003.016949]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Stankiewicz, P., Thiele, H., Schlicker, M., Cseke-Friedrich, A., Bartel-Friedrich, S., Yatsenko, S. A., Lupski, J. R., Hansmann, I.
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<strong>Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia.</strong>
|
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Am. J. Med. Genet. 138A: 11-17, 2005.
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[PubMed: 16097007]
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[Full Text: https://doi.org/10.1002/ajmg.a.30910]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Stevanovic, M., Lovell-Badge, R., Collignon, J., Goodfellow, P. N.
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<strong>SOX3 is an X-linked gene related to SRY.</strong>
|
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Hum. Molec. Genet. 2: 2013-2018, 1993.
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[PubMed: 8111369]
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[Full Text: https://doi.org/10.1093/hmg/2.12.2013]
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</p>
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<p class="mim-text-font">
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Sutton, E., Hughes, J., White, S., Sekido, R., Tan, J., Arboleda, V., Rogers, N., Knower, K., Rowley, L., Eyre, H., Rizzoti, K., McAninch, D., and 10 others.
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<strong>Identification of SOX3 as an XX male sex reversal gene in mice and humans.</strong>
|
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J. Clin. Invest. 121: 328-341, 2011.
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[PubMed: 21183788]
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[Full Text: https://doi.org/10.1172/JCI42580]
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</li>
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<li>
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<p class="mim-text-font">
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Veyrunes, F., Waters, P. D., Miethke, P., Rens, W., McMillan, D., Alsop, A. E., Grutzner, F., Deakin, J. E., Whittington, C. M., Schatzkamer, K., Kremitzki, C. L., Graves, T., Ferguson-Smith, M. A., Warren, W., Graves, J. A. M.
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<strong>Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes.</strong>
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Genome Res. 18: 965-973, 2008.
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[PubMed: 18463302]
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[Full Text: https://doi.org/10.1101/gr.7101908]
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<li>
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<p class="mim-text-font">
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Weiss, J., Meeks, J. J., Hurley, L., Raverot, G., Frassetto, A., Jameson, J. L.
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<strong>Sox3 is required for gonadal function, but not sex determination, in males and females.</strong>
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Molec. Cell. Biol. 23: 8084-8091, 2003.
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[PubMed: 14585968]
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[Full Text: https://doi.org/10.1128/MCB.23.22.8084-8091.2003]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T.
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<strong>Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.</strong>
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Am. J. Hum. Genet. 76: 833-849, 2005.
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[PubMed: 15800844]
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[Full Text: https://doi.org/10.1086/430134]
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<p class="mim-text-font">
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Zipf, W. B., Kelch, R. P., Bacon, G. E.
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<strong>Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males.</strong>
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Clin. Genet. 11: 249-254, 1977.
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[PubMed: 192503]
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[Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb01309.x]
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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Contributors:
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Marla J. F. O'Neill - updated : 1/24/2011<br>Patricia A. Hartz - updated : 9/21/2009<br>Marla J. F. O'Neill - updated : 4/28/2008<br>Anne M. Stumpf - updated : 11/10/2005<br>Victor A. McKusick - updated : 11/4/2005<br>Cassandra L. Kniffin - updated : 9/19/2005<br>Victor A. McKusick - updated : 4/13/2005<br>Victor A. McKusick - updated : 10/12/2004<br>Patricia A. Hartz - updated : 8/9/2004<br>Victor A. McKusick - updated : 2/23/2004<br>Cassandra L. Kniffin - updated : 10/3/2003<br>Victor A. McKusick - updated : 1/8/2003
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 5/23/1994
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Edit History:
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carol : 02/19/2025<br>carol : 04/11/2023<br>carol : 08/20/2021<br>carol : 11/08/2019<br>carol : 02/06/2019<br>carol : 04/26/2011<br>wwang : 2/15/2011<br>terry : 1/24/2011<br>carol : 9/22/2009<br>terry : 9/21/2009<br>wwang : 6/12/2008<br>carol : 5/2/2008<br>ckniffin : 5/1/2008<br>wwang : 4/28/2008<br>alopez : 11/10/2005<br>alopez : 11/10/2005<br>terry : 11/4/2005<br>wwang : 10/31/2005<br>wwang : 9/30/2005<br>ckniffin : 9/19/2005<br>tkritzer : 4/15/2005<br>alopez : 4/13/2005<br>terry : 4/13/2005<br>terry : 4/4/2005<br>tkritzer : 10/14/2004<br>terry : 10/12/2004<br>mgross : 8/11/2004<br>terry : 8/9/2004<br>tkritzer : 2/23/2004<br>terry : 2/23/2004<br>alopez : 10/31/2003<br>carol : 10/3/2003<br>ckniffin : 10/3/2003<br>cwells : 1/13/2003<br>terry : 1/8/2003<br>terry : 5/20/1999<br>dkim : 12/4/1998<br>mark : 12/5/1997<br>mark : 6/25/1996<br>carol : 5/23/1994
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