6578 lines
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Entry
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- *606597 - PAIRED BOX GENE 3; PAX3
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*606597</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606597">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></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 role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000135903;t=ENST00000392070" 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=5077" 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=606597" 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=ENSG00000135903;t=ENST00000392070" 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_000438,NM_001127366,NM_013942,NM_181457,NM_181458,NM_181459,NM_181460,NM_181461" 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_181458" 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=606597" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=09421&isoform_id=09421_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/PAX3" 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/245864,300503,435421,545845,545847,555819,1052862,1172022,1212948,1220350,6654638,7524356,30142096,30142098,31563340,31563342,31563344,31563346,31563348,39645886,62822351,72533358,72533360,72533551,72533682,89130716,119591195,119591196,119591197,119591198,119591199,119591200,119591201,119591202,119591203,158255992,188219638,255046236,1111689908,1111689911,1111689913,2316838009,2316838015,2316838019" 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/P23760" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=5077" 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=ENSG00000135903;t=ENST00000392070" 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=PAX3" 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=PAX3" 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+5077" 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/PAX3" 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:5077" 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/5077" 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=chr2&hgg_gene=ENST00000392070.7&hgg_start=222199887&hgg_end=222298998&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:8617" 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:8617" 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://medlineplus.gov/genetics/gene/pax3" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606597[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=606597[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/PAX3/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/ENSG00000135903" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=PAX3" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=PAX3" 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=PAX3" 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/PAX3" 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=PAX3&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/PA32957" 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:8617" 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/FBgn0001147.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:97487" 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/PAX3#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:97487" 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/5077/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA001688/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5077" 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://zfin.org/ZDB-GENE-080917-53" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5077" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=PAX3&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> 1010606009, 237918004, 702362004<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>
|
|
606597
|
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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PAIRED BOX GENE 3; PAX3
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
PAIRED DOMAIN GENE HuP2; HUP2
|
|
</span>
|
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</h4>
|
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</div>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
PAX3/FKHR FUSION GENE, INCLUDED
|
|
</span>
|
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</div>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PAX3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PAX3</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/1053?start=-3&limit=10&highlight=1053">2q36.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:222199887-222298998&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'})">2:222,199,887-222,298,998</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
|
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|
|
</span>
|
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</p>
|
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</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=122880,268220,193500,148820" 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="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/1053?start=-3&limit=10&highlight=1053">
|
|
2q36.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Craniofacial-deafness-hand syndrome
|
|
|
|
</span>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>Based on amino acid sequence homology and common genomic exon/intron organization (<a href="#25" class="mim-tip-reference" title="Goulding, M. D., Chalepakis, G., Deutsch, U., Erselius, J. R., Gruss, P. <strong>Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.</strong> EMBO J. 10: 1135-1147, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022185</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1991.tb08054.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2022185">Goulding et al., 1991</a>), <a href="#9" class="mim-tip-reference" title="Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G., Noll, M. <strong>Conservation of the paired domain in metazoans and its structure in three isolated human genes.</strong> EMBO J. 8: 1183-1190, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2501086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2501086</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03490.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2501086">Burri et al. (1989)</a> suggested that the human homolog of the mouse Pax3 gene is the HUP2 gene. <a href="#25" class="mim-tip-reference" title="Goulding, M. D., Chalepakis, G., Deutsch, U., Erselius, J. R., Gruss, P. <strong>Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.</strong> EMBO J. 10: 1135-1147, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022185</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1991.tb08054.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2022185">Goulding et al. (1991)</a> found that the product of the mouse Pax3 gene is a DNA-binding protein expressed during early neurogenesis. The HuP2 sequence contains 3 exons, which <a href="#56" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Harris, R., Balling, R., Gruss, P., Strachan, T. <strong>Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.</strong> Nature 355: 635-636, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347148</a>] [<a href="https://doi.org/10.1038/355635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347148">Tassabehji et al. (1992)</a> designated exons 2, 3, and 4 because of their correspondence with exons 2, 3, and 4 of the mouse Pax3 gene, which has 5 exons. <a href="#56" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Harris, R., Balling, R., Gruss, P., Strachan, T. <strong>Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.</strong> Nature 355: 635-636, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347148</a>] [<a href="https://doi.org/10.1038/355635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347148">Tassabehji et al. (1992)</a> found that the HuP2 sequence showed 92% nucleotide homology and 100% amino acid homology with the mouse Pax3 sequence over amino acids 2 to 121. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2501086+1347148+2022185" 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="#59" class="mim-tip-reference" title="Tsukamoto, K., Nakamura, Y., Niikawa, N. <strong>Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues.</strong> Hum. Genet. 93: 270-274, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545913</a>] [<a href="https://doi.org/10.1007/BF00212021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545913">Tsukamoto et al. (1994)</a> cloned PAX3 by 5-prime and 3-prime RACE of an adult cerebellum cDNA library. They identified 2 alternatively spliced isoforms, which they called PAX3A and PAX3B. The deduced PAX3A and PAX3B transcription factors contain 215 and 206 amino acids, respectively. RT-PCR detected high PAX3B expression in esophagus and stomach, with moderate levels in cerebellum, liver, and pancreas. PAX3B was not detected in lung, ovary, uterus, and cardiac muscle. PAX3A was expressed only in cerebellum, esophagus, and skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Barber, T. D., Barber, M. C., Cloutier, T. E., Friedman, T. B. <strong>PAX3 gene structure, alternative splicing and evolution.</strong> Gene 237: 311-319, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521655</a>] [<a href="https://doi.org/10.1016/s0378-1119(99)00339-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521655">Barber et al. (1999)</a> cloned PAX3 from a skeletal muscle cDNA library. They also cloned mouse Pax3. <a href="#5" class="mim-tip-reference" title="Barber, T. D., Barber, M. C., Cloutier, T. E., Friedman, T. B. <strong>PAX3 gene structure, alternative splicing and evolution.</strong> Gene 237: 311-319, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521655</a>] [<a href="https://doi.org/10.1016/s0378-1119(99)00339-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521655">Barber et al. (1999)</a> identified several alternatively spliced isoforms in adult skeletal muscle and in mouse embryos, including 1 that shares significant evolutionary conservation between quail, mouse, and human. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521655" 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="#35" class="mim-tip-reference" title="Macina, R. A., Barr, F. G., Galili, N., Riethman, H. C. <strong>Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma.</strong> Genomics 26: 1-8, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7782066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7782066</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80076-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7782066">Macina et al. (1995)</a> determined that the PAX3 gene contains 8 exons and spans more than 100 kb. Analysis of the intronic translocation breakpoint region associated with alveolar rhabdomyosarcoma (<a href="/entry/268220">268220</a>) revealed a pair of inverted Alu repeats and a pair of inverted (GT)n-rich microsatellite repeats. The 5-prime region contains a microsatellite, putative CAAT, TATA, and CAP sites, and several binding sites for AP1 (see <a href="/entry/165160">165160</a>) and SP1 (<a href="/entry/189906">189906</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7782066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Barber, T. D., Barber, M. C., Cloutier, T. E., Friedman, T. B. <strong>PAX3 gene structure, alternative splicing and evolution.</strong> Gene 237: 311-319, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521655</a>] [<a href="https://doi.org/10.1016/s0378-1119(99)00339-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521655">Barber et al. (1999)</a> determined that the PAX3 gene contains 10 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521655" 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>By analysis of an inversion breakpoint associated with Waardenburg syndrome type 1 (WS1; <a href="/entry/193500">193500</a>), <a href="#60" class="mim-tip-reference" title="Tsukamoto, K., Tohma, T., Ohta, T., Yamakawa, K., Fukushima, Y., Nakamura, Y., Niikawa, N. <strong>Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I.</strong> Hum. Molec. Genet. 1: 315-317, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303207</a>] [<a href="https://doi.org/10.1093/hmg/1.5.315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303207">Tsukamoto et al. (1992)</a> and <a href="#29" class="mim-tip-reference" title="Ishikiriyama, S. <strong>Gene for Waardenburg syndrome type I is located at 2q35, not at 2q37.3. (Letter)</strong> Am. J. Med. Genet. 46: 608, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8322830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8322830</a>] [<a href="https://doi.org/10.1002/ajmg.1320460534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8322830">Ishikiriyama (1993)</a> mapped the PAX3 gene to chromosome 2q35. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1303207+8322830" 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="#7" class="mim-tip-reference" title="Bondurand, N., Pingault, V., Goerich, D. E., Lemort, N., Sock, E., Le Caignec, C., Wegner, M., Goossens, M. <strong>Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome.</strong> Hum. Molec. Genet. 9: 1907-1917, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942418</a>] [<a href="https://doi.org/10.1093/hmg/9.13.1907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10942418">Bondurand et al. (2000)</a> showed that SOX10 (<a href="/entry/602229">602229</a>), in synergy with PAX3, strongly activates MITF (<a href="/entry/156845">156845</a>) expression in transfection assays. Transfection experiments revealed that PAX3 and SOX10 interact directly by binding to a proximal region of the MITF promoter containing binding sites for both factors. Mutant SOX10 or PAX3 proteins failed to transactivate this promoter, providing further evidence that the 2 genes act in concert to directly regulate expression of MITF. In situ hybridization experiments carried out in the dominant megacolon (Dom) mouse confirmed that SOX10 dysfunction impaired Mitf expression as well as melanocytic development and survival. The authors hypothesized that interaction between 3 of the genes that are altered in Waardenburg syndrome (see <a href="/entry/193500">193500</a>) could explain the auditory/pigmentary symptoms of this disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Mutations in the MITF and PAX3 genes, encoding transcriptions factors, are responsible for Waardenburg syndrome 2A (WS2A; <a href="/entry/193510">193510</a>) and WS1 (<a href="/entry/193500">193500</a>)/WS3 (<a href="/entry/148820">148820</a>), respectively. <a href="#54" class="mim-tip-reference" title="Tachibana, M., Takeda, K., Nobukuni, Y., Urabe, K., Long, J. E., Meyers, K. A., Aaronson, S. A., Miki, T. <strong>Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocytes characteristics.</strong> Nature Genet. 14: 50-54, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782819</a>] [<a href="https://doi.org/10.1038/ng0996-50" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8782819">Tachibana et al. (1996)</a> showed that MITF transactivates the gene for tyrosinase (see <a href="/entry/606933">606933</a>), a key enzyme for melanogenesis, and is critically involved in melanocyte differentiation. Absence of melanocytes affects pigmentation in the skin, hair, and eyes, and hearing function in the cochlea. Therefore, hypopigmentation and hearing loss in WS2A are likely to be the results of an anomaly of melanocyte differentiation caused by MITF mutations. <a href="#61" class="mim-tip-reference" title="Watanabe, A., Takeda, K., Ploplis, B., Tachibana, M. <strong>Epistatic relationship between Waardenburg syndrome genes MITF and PAX3.</strong> Nature Genet. 18: 283-286, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9500554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9500554</a>] [<a href="https://doi.org/10.1038/ng0398-283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9500554">Watanabe et al. (1998)</a> showed that PAX3 transactivates the MITF promoter. They further showed that PAX3 proteins associated with WS1 in either the paired domain or the homeodomain failed the recognize and transactivate the MITF promoter. These results provided evidence that PAX3 directly regulates MITF, and suggested that the failure of this regulation due to PAX3 mutations causes the auditory-pigmentary symptoms in at least some individuals with WS1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8782819+9500554" 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="#47" class="mim-tip-reference" title="Ridgeway, A. G., Skerjanc, I. S. <strong>Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2.</strong> J. Biol. Chem. 276: 19033-19039, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11262400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11262400</a>] [<a href="https://doi.org/10.1074/jbc.M011491200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11262400">Ridgeway and Skerjanc (2001)</a> showed that expression of Pax3 induced myogenesis in a mouse pluripotent stem cell line. Pax3 induced expression of the transcription factor Six1 (<a href="/entry/601205">601205</a>), its cofactor Eya2 (<a href="/entry/601654">601654</a>), and the transcription factor Mox1 (<a href="/entry/600147">600147</a>), prior to inducing expression of MyoD (<a href="/entry/159970">159970</a>) and myogenin (<a href="/entry/159980">159980</a>). Expression of dominant-negative Pax3 resulted in loss of expression of Six1, Eya2, and endogenous Pax3, as well as downregulation of Mox1 expression. Pax3 expression had no effect on cardiogenesis in this cell line. <a href="#47" class="mim-tip-reference" title="Ridgeway, A. G., Skerjanc, I. S. <strong>Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2.</strong> J. Biol. Chem. 276: 19033-19039, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11262400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11262400</a>] [<a href="https://doi.org/10.1074/jbc.M011491200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11262400">Ridgeway and Skerjanc (2001)</a> concluded that Pax3 controls a cascade of transcriptional events that are necessary and sufficient for skeletal myogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11262400" 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 Sox10 and Pax3 transcription factors can directly regulate both MITF and RET (<a href="/entry/164761">164761</a>) in a synergistic fashion. <a href="#33" class="mim-tip-reference" title="Lang, D., Epstein, J. A. <strong>Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer.</strong> Hum. Molec. Genet. 12: 937-945, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668617</a>] [<a href="https://doi.org/10.1093/hmg/ddg107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12668617">Lang and Epstein (2003)</a> showed that Pax3 and Sox10 can physically interact; this interaction contributes to synergistic activation of a conserved RET enhancer, and it explains why Sox10 mutants that cannot bind DNA still retain the ability to activate this enhancer in the presence of Pax3. However, in the context of the MITF gene, Pax3 and Sox10 must each bind independently to DNA in order to achieve synergy. These observations appear to explain the phenotype in the mild form of Yemenite deaf-blind syndrome caused by a specific SOX10 mutation (<a href="/entry/602229#0005">602229.0005</a>) in the HMG box that abrogates DNA binding without disrupting association with PAX3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668617" 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="#43" class="mim-tip-reference" title="Pritchard, C., Grosveld, G., Hollenbach, A. D. <strong>Alternative splicing of Pax3 produces a transcriptionally inactive protein.</strong> Gene 305: 61-69, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12594042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12594042</a>] [<a href="https://doi.org/10.1016/s0378-1119(02)01186-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12594042">Pritchard et al. (2003)</a> identified an alternatively spliced isoform of mouse Pax3 produced by skipping exon 8. Deletion of exon 8 removes most of the Pax3 transcriptional activation domain. <a href="#43" class="mim-tip-reference" title="Pritchard, C., Grosveld, G., Hollenbach, A. D. <strong>Alternative splicing of Pax3 produces a transcriptionally inactive protein.</strong> Gene 305: 61-69, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12594042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12594042</a>] [<a href="https://doi.org/10.1016/s0378-1119(02)01186-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12594042">Pritchard et al. (2003)</a> demonstrated that this isoform is transcriptionally inactive, but it can inhibit the activity of the full-length protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12594042" 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="#45" class="mim-tip-reference" title="Relaix, F., Rocancourt, D., Mansouri, A., Buckingham, M. <strong>A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. (Letter)</strong> Nature 435: 948-953, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843801</a>] [<a href="https://doi.org/10.1038/nature03594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843801">Relaix et al. (2005)</a> identified a new cell population that expresses the transcription factors Pax3 and Pax7 (<a href="/entry/167410">167410</a>) but no skeletal muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, <a href="#45" class="mim-tip-reference" title="Relaix, F., Rocancourt, D., Mansouri, A., Buckingham, M. <strong>A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. (Letter)</strong> Nature 435: 948-953, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843801</a>] [<a href="https://doi.org/10.1038/nature03594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843801">Relaix et al. (2005)</a> demonstrated that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a nonmyogenic fate. <a href="#45" class="mim-tip-reference" title="Relaix, F., Rocancourt, D., Mansouri, A., Buckingham, M. <strong>A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. (Letter)</strong> Nature 435: 948-953, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843801</a>] [<a href="https://doi.org/10.1038/nature03594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843801">Relaix et al. (2005)</a> concluded that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Lang, D., Lu, M. M., Huang, L., Engelka, K. A., Zhang, M., Chu, E. Y., Lipner, S., Skoultchi, A., Millar, S. E., Epstein, J. A. <strong>Pax3 functions at a nodal point in melanocyte stem cell differentiation.</strong> Nature 433: 884-887, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15729346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15729346</a>] [<a href="https://doi.org/10.1038/nature03292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15729346">Lang et al. (2005)</a> described the molecular details of a nodal point in adult melanocyte stem cell differentiation in which PAX3 simultaneously functions to initiate a melanogenic cascade while acting downstream to prevent terminal differentiation. PAX3 activates expression of MITF and at the same time competes with MITF for occupancy of an enhancer required for expression of dopachrome tautomerase (<a href="/entry/191275">191275</a>), an enzyme that functions in melanin synthesis. PAX3-expressing melanoblasts are thus committed but undifferentiated until PAX3-mediated repression is relieved by activated beta-catenin (see <a href="/entry/116806">116806</a>). <a href="#34" class="mim-tip-reference" title="Lang, D., Lu, M. M., Huang, L., Engelka, K. A., Zhang, M., Chu, E. Y., Lipner, S., Skoultchi, A., Millar, S. E., Epstein, J. A. <strong>Pax3 functions at a nodal point in melanocyte stem cell differentiation.</strong> Nature 433: 884-887, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15729346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15729346</a>] [<a href="https://doi.org/10.1038/nature03292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15729346">Lang et al. (2005)</a> concluded that a stem cell transcription factor can both determine cell fate and simultaneously maintain an undifferentiated state, leaving a cell poised to differentiate in response to external stimuli. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15729346" 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 mice, <a href="#14" class="mim-tip-reference" title="de Morree, A., Klein, J. D. D., Gan, Q., Farup, J., Urtasun, A., Kanugovi, A., Bilen, B., van Velthoven, C. T. J., Quarta, M., Rando, T. A. <strong>Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function.</strong> Science 366: 734-738, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31699935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31699935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31699935[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aax1694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31699935">de Morree et al. (2019)</a> demonstrated that variation in muscle stem cell activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. <a href="#14" class="mim-tip-reference" title="de Morree, A., Klein, J. D. D., Gan, Q., Farup, J., Urtasun, A., Kanugovi, A., Bilen, B., van Velthoven, C. T. J., Quarta, M., Rando, T. A. <strong>Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function.</strong> Science 366: 734-738, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31699935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31699935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31699935[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aax1694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31699935">De Morree et al. (2019)</a> showed that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1 (SNRNP70; <a href="/entry/180740">180740</a>). Isoforms of the Pax3 mRNA that differed in their 3-prime UTRs were differentially susceptible to regulation by microRNA miR206 (<a href="/entry/611599">611599</a>), which resulted in varying levels of the Pax3 protein in vivo. <a href="#14" class="mim-tip-reference" title="de Morree, A., Klein, J. D. D., Gan, Q., Farup, J., Urtasun, A., Kanugovi, A., Bilen, B., van Velthoven, C. T. J., Quarta, M., Rando, T. A. <strong>Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function.</strong> Science 366: 734-738, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31699935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31699935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31699935[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aax1694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31699935">De Morree et al. (2019)</a> concluded that their findings highlighted a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31699935" 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>PAX3/FKHR Fusion Protein</em></strong></p><p>
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<a href="#21" class="mim-tip-reference" title="Fredericks, W. J., Galili, N., Mukhopadhyay, S., Rovera, G., Bennicelli, J., Barr, F. G., Rauscher, F. J., III. <strong>The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3.</strong> Molec. Cell. Biol. 15: 1522-1535, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7862145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7862145</a>] [<a href="https://doi.org/10.1128/MCB.15.3.1522" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7862145">Fredericks et al. (1995)</a> demonstrated expression of a 97-kD PAX3/FKHR (FOXO1A; <a href="/entry/136533">136533</a>) fusion protein in a t(2;13)-positive rhabdomyosarcoma cell line (see CYTOGENETICS section) and verified that a single polypeptide contained epitopes derived from each protein. The fusion protein was localized to the nucleus in these cells, as was wildtype PAX3 in cells lacking the translocation. They found that DNA binding of the fusion protein was significantly impaired relative to that of PAX3 despite the fact that the 2 proteins had identical PAX DNA-binding domains. However, the fusion protein was a much more potent transcriptional activator than PAX3. Thus, the fusion protein may function as an oncogenic transcription factor by enhancing activation of normal PAX3 target genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7862145" 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="#53" class="mim-tip-reference" title="Sublett, J. E., Jeon, I-S., Shapiro, D. N. <strong>The alveolar rhabdomyosarcoma PAX3/FKHR fusion protein is a transcriptional activator.</strong> Oncogene 11: 545-552, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7630639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7630639</a>]" pmid="7630639">Sublett et al. (1995)</a> found that the PAX3/FKHR hybrid protein binds DNA in vitro in a sequence-specific manner and transactivates the expression of artificial reporter genes, suggesting that its aberrant expression could subvert the transcriptional programs that normally control the growth, differentiation, and survival of primitive myogenic precursors in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7630639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a retroviral vector, <a href="#49" class="mim-tip-reference" title="Scheidler, S., Fredericks, W. J., Rauscher, F. J., III, Barr, F. G., Vogt, P. K. <strong>The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture.</strong> Proc. Nat. Acad. Sci. 93: 9805-9809, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790412</a>] [<a href="https://doi.org/10.1073/pnas.93.18.9805" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8790412">Scheidler et al. (1996)</a> introduced the PAX3/FKHR fusion gene into chicken embryo fibroblasts. Expression of the PAX3/FKHR protein in these cells led to transformation: the cells became enlarged, grew tightly packed and in multiple layers, and acquired the ability for anchorage-independent growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790412" 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 PAX3/FKHR chimeric gene possesses transforming properties. To investigate the actions of these transcription factors, <a href="#31" class="mim-tip-reference" title="Khan, J., Bittner, M. L., Saal, L. H., Teichmann, U., Azorsa, D. O., Gooden, G. C., Pavan, W. J., Trent, J. M., Meltzer, P. S. <strong>cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene.</strong> Proc. Nat. Acad. Sci. 96: 13264-13269, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10557309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10557309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10557309[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.23.13264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10557309">Khan et al. (1999)</a> introduced both PAX3 and PAX3/FKHR into NIH 3T3 cells, and the resultant gene expression changes were analyzed with a mouse cDNA microarray containing 2,225 elements. They found that PAX3/FKHR but not PAX3 activated a myogenic transcription program including the induction of transcription factors Myod (<a href="/entry/159970">159970</a>), myogenin (<a href="/entry/159980">159980</a>), Six1 (<a href="/entry/601205">601205</a>), and Slug (<a href="/entry/602150">602150</a>), as well as a battery of genes involved in several aspects of muscle function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10557309" 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="#48" class="mim-tip-reference" title="Roeb, W., Boyer, A., Cavenee, W. K., Arden, K. C. <strong>PAX3-FOXO1 controls expression of the p57Kip2 cell-cycle regulator through degradation of EGR1.</strong> Proc. Nat. Acad. Sci. 104: 18085-18090, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17986608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17986608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17986608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0708910104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17986608">Roeb et al. (2007)</a> found that myoblasts from transgenic mice expressing PAX3/FOXO1 under control of the PAX3 promoter were unable to complete myogenic differentiation because of an inability to upregulate p57(Kip2) (CDKN1C; <a href="/entry/600856">600856</a>) transcription. This defect was caused by reduced levels of the transcriptional activator Egr1 (<a href="/entry/128990">128990</a>) resulting from a direct, destabilizing interaction with PAX3/FOXO1. Neither PAX3 nor FOXO1 shared the ability to regulate p57(Kip2) transcription. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17986608" 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="#60" class="mim-tip-reference" title="Tsukamoto, K., Tohma, T., Ohta, T., Yamakawa, K., Fukushima, Y., Nakamura, Y., Niikawa, N. <strong>Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I.</strong> Hum. Molec. Genet. 1: 315-317, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303207</a>] [<a href="https://doi.org/10.1093/hmg/1.5.315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303207">Tsukamoto et al. (1992)</a> cloned and characterized an inversion breakpoint of the inv(2)(q35q37.3) paracentric inversion reported by <a href="#28" class="mim-tip-reference" title="Ishikiriyama, S., Tonoki, H., Shibuya, Y., Chin, S., Harada, N., Abe, K., Niikawa, N. <strong>Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3).</strong> Am. J. Med. Genet. 33: 505-507, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2596512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2596512</a>] [<a href="https://doi.org/10.1002/ajmg.1320330419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2596512">Ishikiriyama et al. (1989)</a> in a child with Waardenburg syndrome type 1. Genomic cosmid clones containing the HUP2 gene were isolated from a library constructed from the patient's DNA. One of the clones contained the inversion breakpoint and revealed signals at both 2q35 and 2q37 by fluorescence in situ hybridization, indicating that the HUP2 gene had been disrupted by the inversion. The results suggested that the gene is situated at the more proximal breakpoint 2q35 because one cosmid clone, presumably derived from the normal allele, hybridized only to 2q35. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2596512+1303207" 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>PAX3/FKHR Fusion Gene</em></strong></p><p>
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A frequent finding in alveolar rhabdomyosarcomas is the translocation t(2;13)(q35;q14). <a href="#6" class="mim-tip-reference" title="Barr, F. G., Galili, N., Holick, J., Biegel, J. A., Rovera, G., Emanuel, B. S. <strong>Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma.</strong> Nature Genet. 3: 113-117, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8098985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8098985</a>] [<a href="https://doi.org/10.1038/ng0293-113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8098985">Barr et al. (1993)</a> determined that the PAX3 gene is affected by the t(2;13) translocation associated with alveolar rhabdomyosarcoma. The rearrangement breakpoints occurred within an intron downstream of the paired box and homeodomain-encoding regions. <a href="#22" class="mim-tip-reference" title="Galili, N., Davis, R. J., Fredericks, W. J., Mukhopadhyay, S., Rauscher, F. J., III, Emanuel, B. S., Rovera, G., Barr, F. G. <strong>Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma.</strong> Nature Genet. 5: 230-235, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275086</a>] [<a href="https://doi.org/10.1038/ng1193-230" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8275086">Galili et al. (1993)</a> isolated the chromosome 13 gene that is fused with PAX3 and identified it as a member of the forkhead domain family, which encodes transcription factors containing a conserved DNA-binding motif related to the Drosophila region-specific homeotic gene 'forkhead.' They referred to the gene as FKHR (FOXO1A; <a href="/entry/136533">136533</a>) for 'forkhead in rhabdomyosarcoma.' Thus, disruption of the PAX3 gene can cause either neoplasia or congenital malformation. Other genes that are implicated in both neoplasia and congenital anomalies include the oncogene GLI3 (<a href="/entry/165240">165240</a>), the oncogene RET (<a href="/entry/164761">164761</a>), and the tumor suppressor gene WT1 (<a href="/entry/607102">607102</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8098985+8275086" 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="#56" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Harris, R., Balling, R., Gruss, P., Strachan, T. <strong>Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.</strong> Nature 355: 635-636, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347148</a>] [<a href="https://doi.org/10.1038/355635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347148">Tassabehji et al. (1992)</a> identified variations in the PAX3 gene in 6 of 17 unrelated patients with Waardenburg syndrome type 1 (WS1; <a href="/entry/193500">193500</a>), using primers to amplify exons followed by testing for heteroduplex formation on polyacrylamide gels. No variants were seen in any exon in 50 normal controls. In 3 families that were tested, the variant was found to be familial in 2 and apparently de novo in the third. The variant bands showed perfect linkage to WS in the families studied. One family was found to have a heterozygous 18-bp deletion in the central region of exon 2, resulting in loss of amino acids 29 to 34 (<a href="#0001">606597.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1347148" 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>Simultaneously and independently, <a href="#3" class="mim-tip-reference" title="Baldwin, C. T., Hoth, C. F., Amos, J. A., da-Silva, E. O., Milunsky, A. <strong>An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.</strong> Nature 355: 637-638, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347149</a>] [<a href="https://doi.org/10.1038/355637a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347149">Baldwin et al. (1992)</a> identified a heterozygous mutation in the HuP2 gene (P50L; <a href="#0002">606597.0002</a>) in affected members of a large Brazilian family with Waardenburg syndrome type 1 reported by <a href="#13" class="mim-tip-reference" title="da-Silva, E. O. <strong>Waardenburg I syndrome: a clinical and genetic study of two large Brazilian kindreds, and literature review.</strong> Am. J. Med. Genet. 40: 65-74, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1887852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1887852</a>] [<a href="https://doi.org/10.1002/ajmg.1320400113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1887852">da-Silva (1991)</a>. There were 49 affected persons in 6 generations, and more than 78% of the affected individuals had hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1887852+1347149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Baldwin, C. T., Hoth, C. F., Macina, R. A., Milunsky, A. <strong>Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and review of the literature.</strong> Am. J. Med. Genet. 58: 115-122, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533800</a>] [<a href="https://doi.org/10.1002/ajmg.1320580205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8533800">Baldwin et al. (1995)</a> described 10 additional mutations in the PAX3 gene in families with WS type 1. Eight of these mutations were in a region of PAX3 where only 1 mutation had previously been described. Taken together with previously reported mutations, these mutations covered essentially the entire PAX3 gene. All but 1 of the mutations were 'private;' only 1 mutation had been reported in 2 apparently unrelated families. Preliminary screening for mutations was performed with conformation-sensitive gel electrophoresis (CSGE), as described by <a href="#23" class="mim-tip-reference" title="Ganguly, A., Rock, M. J., Prockop, D. J. <strong>Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes.</strong> Proc. Nat. Acad. Sci. 90: 10325-10329, 1993. Note: Erratum: Proc. Nat. Acad. Sci. 91: 5217 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8234293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8234293</a>] [<a href="https://doi.org/10.1073/pnas.90.21.10325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8234293">Ganguly et al. (1993)</a>. <a href="#4" class="mim-tip-reference" title="Baldwin, C. T., Hoth, C. F., Macina, R. A., Milunsky, A. <strong>Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and review of the literature.</strong> Am. J. Med. Genet. 58: 115-122, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533800</a>] [<a href="https://doi.org/10.1002/ajmg.1320580205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8533800">Baldwin et al. (1995)</a> also cataloged 16 previously reported mutations and 5 chromosomal abnormalities affecting the 2q35 region that were associated with WS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8234293+8533800" 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>Among 24 unrelated individuals with WS1 mutations, <a href="#18" class="mim-tip-reference" title="Farrer, L. A., Arnos, K. S., Asher, J. H., Jr., Baldwin, C. T., Diehl, S. R., Friedman, T. B., Greenberg, J., Grundfast, K. M., Hoth, C., Lalwani, A. K., Landa, B., Leverton, K., Milunsky, A., Morell, R., Nance, W. E., Newton, V., Ramesar, R., Rao, V. S., Reynolds, J. E., San Agustin, T. B., Wilcox, E. R., Winship, I., Read, A. P. <strong>Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes.</strong> Am. J. Hum. Genet. 55: 728-737, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7942851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7942851</a>]" pmid="7942851">Farrer et al. (1994)</a> found that no 2 had the same point mutation in the protein-coding region of PAX3 nor did any of them have a change in the same codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7942851" 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 each of 2 families with WS type 1, <a href="#63" class="mim-tip-reference" title="Wildhardt, G., Winterpacht, A., Hibert, K., Menger, H., Zabel, B. <strong>Two different PAX3 gene mutations causing Waardenburg syndrome type I.</strong> Molec. Cell. Probes 10: 229-231, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8799378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8799378</a>] [<a href="https://doi.org/10.1006/mcpr.1996.0032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8799378">Wildhardt et al. (1996)</a> described the causative PAX3 mutation. One mutation was an insertion in the paired box domain resulting in a protein termination within the paired box. The second mutation was a single-basepair substitution producing an arg271-to-cys amino acid change in the homeobox region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8799378" 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 the 'Splotch-delayed' mouse, mutation in the Pax3 paired domain (G9R) abrogates the DNA-binding activity of both the paired domain and the homeodomain, suggesting that they may functionally interact. To investigate this possibility further, <a href="#20" class="mim-tip-reference" title="Fortin, A. S., Underhill, D. A., Gros, P. <strong>Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain.</strong> Hum. Molec. Genet. 6: 1781-1790, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302254</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1781" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302254">Fortin et al. (1997)</a> analyzed the DNA binding properties of additional point mutations in the PAX3 paired domain and homeodomain that occur in Waardenburg syndrome patients. Within the paired domain, 7 of 10 mutations were found to abrogate DNA binding by the paired domain. Remarkably, these 7 mutations also affected DNA binding by the homeodomain, causing either a complete loss, a reduction, or an increase in DNA-binding activity. In addition, the effect of paired domain mutations occurred at the level of monomer formation by the homeodomain, while the dimerization potential of this domain seemed unaffected in mutants where it could be analyzed. One mutation in the homeodomain also abrogated DNA binding by the paired domain. The observation that independent mutations in either domain can affect DNA binding by the other in the intact PAX3 protein strongly suggests that the 2 domains are not functionally independent but bind DNA through cooperative interactions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302254" 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="#55" class="mim-tip-reference" title="Tassabehji, M., Newton, V. E., Liu, X.-Z., Brady, A., Donnai, D., Krajewska-Walasek, M., Murday, V., Norman, A., Obersztyn, E., Reardon, W., Rice, J. C., Trembath, R., Wieacker, P., Whiteford, M., Winter, R., Read, A. P. <strong>The mutational spectrum in Waardenburg syndrome.</strong> Hum. Molec. Genet. 4: 2131-2137, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589691</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589691">Tassabehji et al. (1995)</a> reported the results of screening for mutations in the PAX3 and MITF genes (<a href="/entry/156845">156845</a>) in 134 families or individuals with auditory-pigmentary syndromes, such as Waardenburg syndrome or probable neural cristopathies. PAX3 mutations were found in 20 of 25 families with definite WS1 and 1 of 2 with WS3 (<a href="/entry/148820">148820</a>), but in none of 23 with definite type WS2 (see <a href="/entry/193510">193510</a>) or 36 with other neural cristopathies. The latter category included 12 with Hirschsprung disease plus pigmentary disturbances (WS4; see <a href="/entry/277580">277580</a>). They concluded that about 20% of cases of WS2 are caused by mutations in MITF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589691" 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="#66" class="mim-tip-reference" title="Zlotogora, J., Lerer, I., Bar-David, S., Ergaz, Z., Abeliovich, D. <strong>Homozygosity for Waardenburg syndrome.</strong> Am. J. Hum. Genet. 56: 1173-1178, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726174</a>]" pmid="7726174">Zlotogora et al. (1995)</a> reported a large kindred in which many individuals had Waardenburg syndrome type 1 associated with a heterozygous mutation in the PAX3 gene (S84F; <a href="#0009">606597.0009</a>). However, there was 1 child, born of consanguineous parents, who had a severe phenotype consistent with WS type 3 (<a href="/entry/148820">148820</a>): this patient was found to be homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects. Since all Pax3 mutations in mice lead to severe neural tube defects and intrauterine or neonatal death, the survival of the homozygote in this case and the absence of neural tube defects were unexpected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726174" 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 2 unrelated Chinese patients with Waardenburg syndrome type 1, <a href="#12" class="mim-tip-reference" title="Chen, H., Jiang, L., Xie, Z., Mei, L., He, C., Hu, Z., Xia, K., Feng, Y. <strong>Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome.</strong> Biochem. Biophys. Res. Commun. 397: 70-74, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20478267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20478267</a>] [<a href="https://doi.org/10.1016/j.bbrc.2010.05.066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20478267">Chen et al. (2010)</a> identified 2 different heterozygous mutations in the PAX3 gene (<a href="#0015">606597.0015</a> and <a href="#0016">606597.0016</a>, respectively). <a href="#65" class="mim-tip-reference" title="Zhang, H., Chen, H., Luo, H., An, J., Sun, L., Mei, L., He, C., Jiang, L., Jiang, W., Xia, K., Li, J.-D., Feng, Y. <strong>Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.</strong> Hum. Genet. 131: 491-503, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21965087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21965087</a>] [<a href="https://doi.org/10.1007/s00439-011-1098-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21965087">Zhang et al. (2012)</a> performed in vitro functional expression studies showed that the mutant proteins had decreased or abolished ability to transactivate the MITF promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21965087+20478267" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The work of <a href="#8" class="mim-tip-reference" title="Bosher, S. K., Hallpike, C. S. <strong>Observations on the histogenesis of the inner ear degeneration of the deaf white cat and its possible relationship to the aetiology of certain unexplained varieties of human congenital deafness.</strong> J. Laryng. 80: 222-235, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5907833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5907833</a>] [<a href="https://doi.org/10.1017/s0022215100065191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5907833">Bosher and Hallpike (1966)</a> on an animal analog, deaf white cats, suggested that destruction of the inner ear mechanism occurs in the first days of extrauterine life and was correlated with an inability to regulate properly the constitution of the endolymphatic fluid. The cat, like man, may escape deafness in one or both ears. If more of the factors that lead to retention of hearing were known, deafness might be preventable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5907833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Motohashi, H., Hozawa, K., Oshima, T., Takeuchi, T., Takasaka, T. <strong>Dysgenesis of melanocytes and cochlear dysfunction in mutant microphthalmia (mi) mice.</strong> Hear. Res. 80: 10-20, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7852195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7852195</a>] [<a href="https://doi.org/10.1016/0378-5955(94)90003-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7852195">Motohashi et al. (1994)</a> pointed out that melanocytes are a normal component of the inner ear, including the stria vascularis. There are 3 known mutations in the mouse which lead to a deficiency of melanocytes in mast cells: white dominant spotting (W), Steel (Sl), and microphthalmia (mi). All 3 mutants have a thin stria vascularis, without melanocyte-like intermediate cells, and severe impairment of hearing. Thus, the absence of intermediate cells or melanocytes causes severe hearing loss. The absence of melanin has little influence on hearing acuity because albino mice without melanin have no impairment of hearing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7852195" 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>Other genes in the 9q34 band have homologs on mouse chromosome 2. In the mouse, the 'lethal-spotted' (ls) mutation, which results not only in spotting but also in failure of the entire ganglia to colonize the gut, is located on chromosome 2. <a href="#30" class="mim-tip-reference" title="Jacobs-Cohen, R. J., Payette, R. F., Gershon, M. D., Rothman, T. P. <strong>Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive environment.</strong> J. Comp. Neurol. 255: 425-438, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3819023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3819023</a>] [<a href="https://doi.org/10.1002/cne.902550309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3819023">Jacobs-Cohen et al. (1987)</a> found that in lethal spotting piebald (ls/ls) mice, who develop megacolon, the terminal 2 mm of intestine does not become colonized by neural crest cells, resulting in aganglionosis. Neural crest cells transplanted from areas around the neural tube (primary explants) or foregut (secondary explants) did not colonize the terminal portions of the hindgut. These findings suggested that the nonneuronal components are abnormal, preventing migration of normal neural crest derivatives into the bowel wall. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3819023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Epstein, D. J., Malo, D., Vekemans, M., Gros, P. <strong>Molecular characterization of a deletion encompassing the Splotch mutation on mouse chromosome 1.</strong> Genomics 10: 89-93, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2045114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2045114</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90488-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2045114">Epstein et al. (1991)</a> studied a deletion of mouse chromosome 1 that involved the 'splotch' locus. The murine equivalent of the ALPP gene was included in the deletion, thus supporting the notion that 'splotch' is the equivalent of WS1. Furthermore, <a href="#16" class="mim-tip-reference" title="Epstein, D. J., Vekemans, M., Gros, P. <strong>Splotch (Sp-2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3.</strong> Cell 67: 767-774, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1682057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1682057</a>] [<a href="https://doi.org/10.1016/0092-8674(91)90071-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1682057">Epstein et al. (1991)</a> mapped the paired box gene Pax3 to a region near or at the Sp locus on mouse chromosome 1 and found Pax3 to be deleted in mice heterozygous for a splotch allele. In another allelic variant of splotch, they found deletion of 32 nucleotides in the Pax3 mRNA transcript and gene. The deletion was located within the paired homeodomain of Pax3 and was predicted to create a truncated protein as a result of a newly created termination codon at the deletion breakpoint. The splotch mutation is associated in the mouse with spina bifida and exencephaly. The findings were interpreted to indicate that Pax3 plays a key role in normal neural development. <a href="#38" class="mim-tip-reference" title="Moase, C. E., Trasler, D. G. <strong>Splotch locus mouse mutants: models for neural tube defects and Waardenburg syndrome type I in humans.</strong> J. Med. Genet. 29: 145-151, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1552554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1552554</a>] [<a href="https://doi.org/10.1136/jmg.29.3.145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1552554">Moase and Trasler (1992)</a> reviewed the subject of the splotch locus in mouse mutants. <a href="#52" class="mim-tip-reference" title="Steel, K. P., Smith, R. J. H. <strong>Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1.</strong> Nature Genet. 2: 75-79, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303254</a>] [<a href="https://doi.org/10.1038/ng0992-75" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303254">Steel and Smith (1992)</a> found that, unlike individuals with Waardenburg syndrome, the splotch mouse has normal hearing. They suggested that the difference in expression of the genes in the 2 species may result from different parts of the gene being mutated or from modifying influences as yet undefined. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2045114+1552554+1682057+1303254" 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="Epstein, D. J., Vogan, K. J., Trasler, D. G., Gros, P. <strong>A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the Splotch (Sp) mouse mutant.</strong> Proc. Nat. Acad. Sci. 90: 532-536, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8421686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8421686</a>] [<a href="https://doi.org/10.1073/pnas.90.2.532" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8421686">Epstein et al. (1993)</a> demonstrated that in the original, spontaneously arising Sp allele, a complex mutation in the PAX3 gene had occurred, including an A-to-T transversion at the invariant 3-prime AG splice acceptor of intron 3. This mutation abrogated the normal splicing of intron 3, resulting in the generation of 4 aberrantly spliced mRNA transcripts. Two of the transcripts made use of cryptic 3-prime splice sites within the downstream exon, generating small deletions which disrupted the reading frame of the transcripts. A third aberrant splicing event resulted in the deletion of exon 4, while a fourth retained intron 3. None of these mutations would be expected to result in functional PAX3 proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8421686" 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="Asher, J. H., Jr., Harrison, R. W., Morell, R., Carey, M. L., Friedman, T. B. <strong>Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: a murine model of Waardenburg syndrome variation.</strong> Genomics 34: 285-298, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786127</a>] [<a href="https://doi.org/10.1006/geno.1996.0289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8786127">Asher et al. (1996)</a> stated that over 50 human PAX3 mutations leading to hearing, craniofacial, limb, and pigmentation anomalies had been identified. Variability in penetrance and expressivity is observed in humans with PAX3 mutations and in mice with 'splotch' mutations. In mice with certain 'splotch' mutations, influence of the genetic background and sex of the individual on penetrance and expressivity is demonstrable. <a href="#1" class="mim-tip-reference" title="Asher, J. H., Jr., Harrison, R. W., Morell, R., Carey, M. L., Friedman, T. B. <strong>Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: a murine model of Waardenburg syndrome variation.</strong> Genomics 34: 285-298, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786127</a>] [<a href="https://doi.org/10.1006/geno.1996.0289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8786127">Asher et al. (1996)</a> described a murine model for Waardenburg syndrome variation and concluded that a minimum of 2 genes interact with the 'splotch' mutation to influence the craniofacial features of these mice. One of these genes may be either X-linked or sex-influenced, while the other is autosomal. They stated that these studies in mice may lead to the identification of genes that modify the expression of human PAX3 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8786127" 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="#19" class="mim-tip-reference" title="Fleming, A., Copp, A. J. <strong>A genetic risk factor for mouse neural tube defects: defining the embryonic basis.</strong> Hum. Molec. Genet. 9: 575-581, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699180</a>] [<a href="https://doi.org/10.1093/hmg/9.4.575" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10699180">Fleming and Copp (2000)</a> exploited variations in the normal pattern of cranial neural tube closure (closure 2) among inbred mouse strains. Strains with a more caudal location of cranial neural tube closure (e.g., DBA/2) were relatively resistant to neural tube defects (NTDs), whereas strains with a rostrally positioned closure 2 (e.g., NZW) exhibited increased susceptibility to NTDs. The authors back-crossed the 'splotch' (Sp2H) mutant gene onto both the DBA/2 and NZW backgrounds. After transfer to the DBA/2 background, the frequency of cranial NTDs was reduced significantly in Sp2H homozygotes, confirming a protective effect of caudal closure 2. In contrast, Sp2H homozygotes on the NZW background had a persistently high frequency of cranial NTDs. The frequency of spina bifida was not altered in either backcross, emphasizing the specificity of this genetic effect for cranial neurulation only. The authors concluded that variation in the pattern of cranial neural tube closure is a genetically determined factor influencing susceptibility to cranial NTDs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Lagutina, I., Conway, S. J., Sublett, J., Grosveld, G. C. <strong>Pax3-FKHR knock-in mice show developmental aberrations but do not develop tumors.</strong> Molec. Cell. Biol. 22: 7204-7216, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12242297[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.22.20.7204-7216.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242297">Lagutina et al. (2002)</a> generated mice carrying a Pax3-Fkhr knockin allele. Despite low expression of this allele, heterozygous offspring of Pax3-Fkhr chimeric mice showed developmental abnormalities, including intraventricular septum defects, tricuspid valve insufficiency, and diaphragm defects, which caused congestive heart failure leading to perinatal death. Heterozygotes also displayed malformations of some, but not all, hypaxial muscles. However, neither newborn heterozygous pups nor their chimeric parents showed any signs of malignancy. <a href="#32" class="mim-tip-reference" title="Lagutina, I., Conway, S. J., Sublett, J., Grosveld, G. C. <strong>Pax3-FKHR knock-in mice show developmental aberrations but do not develop tumors.</strong> Molec. Cell. Biol. 22: 7204-7216, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12242297[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.22.20.7204-7216.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242297">Lagutina et al. (2002)</a> concluded that the Pax2-Fkhr allele causes lethal developmental defects in knockin mice but is insufficient to cause muscle tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12242297" 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="#44" class="mim-tip-reference" title="Relaix, F., Polimeni, M., Rocancourt, D., Ponzetto, C., Schafer, B. W., Buckingham, M. <strong>The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo.</strong> Genes Dev. 17: 2950-2965, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14665670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14665670</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14665670[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.281203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14665670">Relaix et al. (2003)</a> found that mice expressing Pax3/Fkhr displayed developmental defects, including ectopic delamination and inappropriate migration of muscle precursor cells. These events resulted from overexpression of Met (<a href="/entry/164860">164860</a>), leading to constitutive activation of Met signaling. The gain-of-function phenotype was also characterized by overactivation of MyoD (<a href="/entry/159970">159970</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14665670" 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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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>16 Selected Examples</a>):</strong>
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<a href="/allelicVariants/606597" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606597[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 WAARDENBURG SYNDROME, TYPE 1</strong>
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PAX3, 18-BP DEL, EX2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1559320436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1559320436;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1559320436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1559320436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004425" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004425" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004425</a>
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<p>In a kindred with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), <a href="#56" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Harris, R., Balling, R., Gruss, P., Strachan, T. <strong>Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.</strong> Nature 355: 635-636, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347148</a>] [<a href="https://doi.org/10.1038/355635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347148">Tassabehji et al. (1992)</a> demonstrated a heterozygous deletion of 18 bp from the central region of exon 2 of the PAX3 gene. This resulted in loss of amino acids 29 to 34 of the paired domain. The deleted sequence ran between 2 directly repeated GGCCC sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1347148" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 WAARDENBURG SYNDROME, TYPE 1</strong>
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PAX3, PRO50LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893650;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004426" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004426" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004426</a>
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<p>In affected members of a Brazilian family with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>) reported by <a href="#13" class="mim-tip-reference" title="da-Silva, E. O. <strong>Waardenburg I syndrome: a clinical and genetic study of two large Brazilian kindreds, and literature review.</strong> Am. J. Med. Genet. 40: 65-74, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1887852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1887852</a>] [<a href="https://doi.org/10.1002/ajmg.1320400113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1887852">da-Silva (1991)</a>, <a href="#3" class="mim-tip-reference" title="Baldwin, C. T., Hoth, C. F., Amos, J. A., da-Silva, E. O., Milunsky, A. <strong>An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.</strong> Nature 355: 637-638, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347149</a>] [<a href="https://doi.org/10.1038/355637a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347149">Baldwin et al. (1992)</a> identified a heterozygous G-to-A transition 64 bases downstream from the 5-prime end of exon 2. This changed codon CCG (proline) to CTG (leucine) in the sense strand. Amino acid residue 50 was thought to be involved (<a href="#37" class="mim-tip-reference" title="Milunsky, A. <strong>Personal Communication.</strong> Boston, Mass. 3/4/1992."None>Milunsky, 1992</a>), thus resulting in a pro50-to-leu (P50L) substitution. <a href="#3" class="mim-tip-reference" title="Baldwin, C. T., Hoth, C. F., Amos, J. A., da-Silva, E. O., Milunsky, A. <strong>An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.</strong> Nature 355: 637-638, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347149</a>] [<a href="https://doi.org/10.1038/355637a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347149">Baldwin et al. (1992)</a> noted that there were 49 affected persons in 6 generations, and more than 78% of the affected individuals had hearing loss. All 26 affected members of the family were heterozygous for the mutation, whereas all 34 unaffected members and 50 control subjects were homozygous for the wildtype allele. <a href="#3" class="mim-tip-reference" title="Baldwin, C. T., Hoth, C. F., Amos, J. A., da-Silva, E. O., Milunsky, A. <strong>An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.</strong> Nature 355: 637-638, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347149</a>] [<a href="https://doi.org/10.1038/355637a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1347149">Baldwin et al. (1992)</a> did not detect the P50L mutation in 17 unrelated WS1 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1887852+1347149" 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 WAARDENBURG SYNDROME, TYPE 1</strong>
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PAX3, 14-BP DEL, EX2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1559320252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1559320252;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1559320252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1559320252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004427" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004427" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004427</a>
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<p>In an Indonesian family with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), <a href="#39" class="mim-tip-reference" title="Morell, R., Friedman, T. B., Moeljopawiro, S., Hartono, (NI), Soewito, (NI), Asher, J. H., Jr. <strong>A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.</strong> Hum. Molec. Genet. 1: 243-247, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303193</a>] [<a href="https://doi.org/10.1093/hmg/1.4.243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303193">Morell et al. (1992)</a> identified a 14-bp deletion in the paired domain encoded by exon 2 of the PAX3 gene. The frameshift mutation resulted in a premature termination codon in exon 3. The gene product was a truncated protein lacking most of the paired domain and all of the predicted homeodomain. The deletion started with the last 2 nucleotides of codon 158 and extended through codon 162 of the paired box. <a href="#39" class="mim-tip-reference" title="Morell, R., Friedman, T. B., Moeljopawiro, S., Hartono, (NI), Soewito, (NI), Asher, J. H., Jr. <strong>A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.</strong> Hum. Molec. Genet. 1: 243-247, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303193</a>] [<a href="https://doi.org/10.1093/hmg/1.4.243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303193">Morell et al. (1992)</a> discussed whether the phenotypic effects of the mutation are due to haploinsufficiency of the product protein or to a transdominant negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303193" 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>.0004 WAARDENBURG SYNDROME, TYPE 1</strong>
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PAX3, 1-BP DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004428" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004428" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004428</a>
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<p>In a family with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), designated WS.06, <a href="#57" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T. <strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong> Nature Genet. 3: 26-30, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>] [<a href="https://doi.org/10.1038/ng0193-26" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490648">Tassabehji et al. (1993)</a> demonstrated a frameshift mutation in the PAX3 gene. The deletion of the last nucleotide in codon 63 in exon 2 led to premature termination, with amino acid residue 75 corresponding to the beginning of exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 WAARDENBURG SYNDROME, TYPE 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1559316535 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1559316535;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1559316535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1559316535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004429 OR RCV002272009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004429, RCV002272009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004429...</a>
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<p>In a family with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), designated WS.11, <a href="#57" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T. <strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong> Nature Genet. 3: 26-30, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>] [<a href="https://doi.org/10.1038/ng0193-26" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490648">Tassabehji et al. (1993)</a> demonstrated a 2-bp deletion in exon 4 of the PAX3 gene that removed one of a tandemly repeated pair of CA dinucleotides. The deletion in exon 4 presumably led to premature termination in exon 5, abolishing the homeodomain. In this family and in 2 others, <a href="#57" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T. <strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong> Nature Genet. 3: 26-30, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>] [<a href="https://doi.org/10.1038/ng0193-26" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490648">Tassabehji et al. (1993)</a> used the ARMS method, the amplification refractory mutation system (<a href="#41" class="mim-tip-reference" title="Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., Markham, A. F. <strong>Analysis of any point mutation in DNA: the amplification refractory mutation system (ARMS).</strong> Nucleic Acids Res. 17: 2503-2516, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2785681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2785681</a>] [<a href="https://doi.org/10.1093/nar/17.7.2503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2785681">Newton et al., 1989</a>), to confirm that affected family members had the mutation and that no unaffected family member was carrying the alteration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490648+2785681" 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>This mutation is designated 556delCA based on the sequencing of <a href="#27" class="mim-tip-reference" title="Hoth, C. F., Milunsky, A., Lipsky, N., Sheffer, R., Clarren, S. K., Baldwin, C. T. <strong>Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).</strong> Am. J. Hum. Genet. 52: 455-462, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8447316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8447316</a>]" pmid="8447316">Hoth et al. (1993)</a> (see also <a href="#55" class="mim-tip-reference" title="Tassabehji, M., Newton, V. E., Liu, X.-Z., Brady, A., Donnai, D., Krajewska-Walasek, M., Murday, V., Norman, A., Obersztyn, E., Reardon, W., Rice, J. C., Trembath, R., Wieacker, P., Whiteford, M., Winter, R., Read, A. P. <strong>The mutational spectrum in Waardenburg syndrome.</strong> Hum. Molec. Genet. 4: 2131-2137, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589691</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589691">Tassabehji et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8589691+8447316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908111 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908111;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776586 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776586;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587776586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs587776586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>This variant, originally reported as a GLY48ALA substitution by <a href="#57" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T. <strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong> Nature Genet. 3: 26-30, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>] [<a href="https://doi.org/10.1038/ng0193-26" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490648">Tassabehji et al. (1993)</a> has been reclassified as a GLY81ALA substitution based on the sequencing of <a href="#27" class="mim-tip-reference" title="Hoth, C. F., Milunsky, A., Lipsky, N., Sheffer, R., Clarren, S. K., Baldwin, C. T. <strong>Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).</strong> Am. J. Hum. Genet. 52: 455-462, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8447316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8447316</a>]" pmid="8447316">Hoth et al. (1993)</a> (see <a href="#55" class="mim-tip-reference" title="Tassabehji, M., Newton, V. E., Liu, X.-Z., Brady, A., Donnai, D., Krajewska-Walasek, M., Murday, V., Norman, A., Obersztyn, E., Reardon, W., Rice, J. C., Trembath, R., Wieacker, P., Whiteford, M., Winter, R., Read, A. P. <strong>The mutational spectrum in Waardenburg syndrome.</strong> Hum. Molec. Genet. 4: 2131-2137, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589691</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589691">Tassabehji et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8447316+8490648+8589691" 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="#57" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T. <strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong> Nature Genet. 3: 26-30, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>] [<a href="https://doi.org/10.1038/ng0193-26" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490648">Tassabehji et al. (1993)</a> found a GGC-to-GCC transversion in the PAX3 gene, resulting in a gly-to-ala substitution, in a family (WS.15) presumed to have Waardenburg syndrome type 2 (<a href="/entry/193510">193510</a>) with normal inner canthal distance. However, although 1 individual by measurement said to have an inner canthal distance at the 65th percentile, the photograph (their Figure 4) certainly suggested dystopia canthorum. The affected individual I-2 had a W index of 2.21 but was the only member of the family with a value over 2.07, which is the threshold recommended by the Waardenburg Consortium. The family reported by <a href="#57" class="mim-tip-reference" title="Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T. <strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong> Nature Genet. 3: 26-30, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>] [<a href="https://doi.org/10.1038/ng0193-26" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490648">Tassabehji et al. (1993)</a> was later considered by <a href="#55" class="mim-tip-reference" title="Tassabehji, M., Newton, V. E., Liu, X.-Z., Brady, A., Donnai, D., Krajewska-Walasek, M., Murday, V., Norman, A., Obersztyn, E., Reardon, W., Rice, J. C., Trembath, R., Wieacker, P., Whiteford, M., Winter, R., Read, A. P. <strong>The mutational spectrum in Waardenburg syndrome.</strong> Hum. Molec. Genet. 4: 2131-2137, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589691</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589691">Tassabehji et al. (1995)</a> to have Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8589691+8490648" 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="#46" class="mim-tip-reference" title="Reynolds, J. E., Meyer, J. M., Landa, B., Stevens, C. A., Arnos, K. S., Israel, J., Marazita, M. L., Bodurtha, J., Nance, W. E., Diehl, S. R. <strong>Analysis of variability of clinical manifestations in Waardenburg syndrome.</strong> Am. J. Med. Genet. 57: 540-547, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573125</a>] [<a href="https://doi.org/10.1002/ajmg.1320570405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7573125">Reynolds et al. (1995)</a> reviewed a collection of 26 WS1 and 8 WS2 families and concluded that the W-index as a means of discriminating between affected WS1 and WS2 individuals 'may be problematic' because (1) ranges of W-index scores of affected and unaffected individuals overlapped considerably within both WS1 and WS2 families, and (2) a considerable number of both affected and unaffected WS2 individuals exhibited W-index scores consistent with dystopia canthorum. This classification of families might have implications for risk assessment of deafness, since WS2 families had been shown to have greater incidence of deafness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573125" 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>'Splotch' is an established mouse model for neural tube defects (NTD). Furthermore, in the human, neural tube defects are occasionally associated with Waardenburg syndrome (<a href="#10" class="mim-tip-reference" title="Carezani-Gavin, M., Clarren, S. K., Steege, T. <strong>Waardenburg syndrome associated with meningomyelocele. (Letter)</strong> Am. J. Med. Genet. 42: 135-136, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1308353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1308353</a>] [<a href="https://doi.org/10.1002/ajmg.1320420127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1308353">Carezani-Gavin et al., 1992</a>; <a href="#11" class="mim-tip-reference" title="Chatkupt, S., Chatkupt, S., Johnson, W. G. <strong>Waardenburg syndrome and myelomeningocele in a family.</strong> J. Med. Genet. 30: 83-84, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8423616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8423616</a>] [<a href="https://doi.org/10.1136/jmg.30.1.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8423616">Chatkupt et al., 1993</a>). <a href="#26" class="mim-tip-reference" title="Hol, F. A., Hamel, B. C. J., Geurds, M. P. A., Mullaart, R. A., Barr, F. G., Macina, R. A., Mariman, E. C. M. <strong>A frameshift mutation in the gene for PAX3 in a girl with spina bifida and mild signs of Waardenburg syndrome.</strong> J. Med. Genet. 32: 52-56, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7897628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7897628</a>] [<a href="https://doi.org/10.1136/jmg.32.1.52" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7897628">Hol et al. (1995)</a> screened the PAX3 gene in 39 patients with familial NTD, using single-strand conformation analysis. One patient with lumbosacral meningomyelocele was found to have a 5-bp deletion in exon 5, approximately 55 bp upstream of the conserved homeodomain. The deletion of CAA (gln) and TC caused a frameshift with a stop codon almost immediately after the mutated site; the frameshift led to the insertion of an arg residue before the creation of the stop codon. The patient was found to show mild signs of WS1 (<a href="/entry/193500">193500</a>). Varying signs of this syndrome were found to cosegregate with the mutation in the family. The results supported the hypothesis that mutations in the gene for PAX3 can also predispose to NTD. It is noteworthy that whereas homozygous Splotch mouse embryos can have NTD, in the heterozygous state mutations of the PAX3 gene do not cause but seem to predispose to NTD in a strain-specific manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7897628+1308353+8423616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893651;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004432 OR RCV000004433 OR RCV003555913" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004432, RCV000004433, RCV003555913" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004432...</a>
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<p>In affected members of a large kindred with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), <a href="#66" class="mim-tip-reference" title="Zlotogora, J., Lerer, I., Bar-David, S., Ergaz, Z., Abeliovich, D. <strong>Homozygosity for Waardenburg syndrome.</strong> Am. J. Hum. Genet. 56: 1173-1178, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726174</a>]" pmid="7726174">Zlotogora et al. (1995)</a> identified a heterozygous mutation in exon 2 of the PAX3 gene, resulting in a ser84-to-phe (S84F) substitution. However, there was 1 child, born of consanguineous parents, who had a severe phenotype consistent with WS type 3 (<a href="/entry/148820">148820</a>): this patient was found to be homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects. Since all Pax3 mutations in mice lead to severe neural tube defects and intrauterine or neonatal death, the survival of the homozygote in this case and the absence of neural tube defects were unexpected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893652;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004434 OR RCV003229799" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004434, RCV003229799" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004434...</a>
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<p>Craniofacial-deafness-hand syndrome (<a href="/entry/122880">122880</a>) was described by <a href="#51" class="mim-tip-reference" title="Sommer, A., Young-Wee, T., Frye, T. <strong>Previously undescribed syndrome of craniofacial, hand anomalies, and sensorineural deafness.</strong> Am. J. Med. Genet. 15: 71-77, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6859126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6859126</a>] [<a href="https://doi.org/10.1002/ajmg.1320150109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6859126">Sommer et al. (1983)</a> in a mother and 2 children with absence or hypoplasia of the nasal bones, hypoplastic maxilla, small and sharp nose with thin nares, limited movement of the wrist, short palpebral fissures, ulnar deviation of the fingers, hypertelorism, and profound sensorineural deafness. <a href="#2" class="mim-tip-reference" title="Asher, J. H., Jr., Sommer, A., Morrell, R., Friedman, T. B. <strong>Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome.</strong> Hum. Mutat. 7: 30-35, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664898</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8664898">Asher et al. (1996)</a> demonstrated a PAX3 exon 2 missense mutation, asn47-to-lys (N47K), in the affected members of this family. The affected persons were heterozygous for the mutation. A missense mutation in the same codon, asn47-to-his (<a href="#0011">606597.0011</a>), gave rise to Waardenburg syndrome type 3. CDHS is clinically distinct from WS3, since affected individuals in the former did not have either muscle or skeletal upper limb hypoplasia; and in families with WS3, a 'pursed' appearance of the mouth and hypoplasia or absence of the nasal bone have not been described. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8664898+6859126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893653 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893653;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004435" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004435" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004435</a>
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<p>In affected members of a family with Waardenburg syndrome type 3 (<a href="/entry/148820">148820</a>) studied by <a href="#24" class="mim-tip-reference" title="Goodman, R. M., Lewithal, I., Solomon, A., Klein, D. <strong>Upper limb involvement in the Klein-Waardenburg syndrome.</strong> Am. J. Med. Genet. 11: 425-433, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7091186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7091186</a>] [<a href="https://doi.org/10.1002/ajmg.1320110407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7091186">Goodman et al. (1982)</a> and <a href="#50" class="mim-tip-reference" title="Sheffer, R., Zlotogora, J. <strong>Autosomal dominant inheritance of Klein-Waardenburg syndrome.</strong> Am. J. Med. Genet. 42: 320-322, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1536170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1536170</a>] [<a href="https://doi.org/10.1002/ajmg.1320420312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1536170">Sheffer and Zlotogora (1992)</a>, <a href="#36" class="mim-tip-reference" title="Milunsky, A., Lipsky, N., Sheffer, R., Zlotogora, J., Baldwin, C. <strong>A mutation in the Waardenburg syndrome (WS-I) gene in a family with 'WS-III'. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A222, 1992."None>Milunsky et al. (1992)</a> and <a href="#27" class="mim-tip-reference" title="Hoth, C. F., Milunsky, A., Lipsky, N., Sheffer, R., Clarren, S. K., Baldwin, C. T. <strong>Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).</strong> Am. J. Hum. Genet. 52: 455-462, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8447316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8447316</a>]" pmid="8447316">Hoth et al. (1993)</a> identified a heterozygous 352A-C transversion in exon 2 of the PAX3 gene, resulting in an asn47-to-his (N47H) substitution in the paired domain. In addition to telecanthus, blepharophimosis, and hearing loss, affected individuals had hypoplasia of the upper limbs. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7091186+8447316+1536170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 WAARDENBURG SYNDROME, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1559318494 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1559318494;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1559318494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1559318494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004436" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004436" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004436</a>
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<p><a href="#58" class="mim-tip-reference" title="Tekin, M., Bodurtha, J. N., Nance, W. E., Pandya, A. <strong>Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome?</strong> Clin. Genet. 60: 301-304, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11683776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11683776</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.600408.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11683776">Tekin et al. (2001)</a> described a mother and son with typical clinical findings of WS type 3 (<a href="/entry/148820">148820</a>) segregating with a heterozygous 13-bp deletion in the paired domain in exon 3 of the PAX3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11683776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893654;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104893654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004437" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004437" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004437</a>
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<p><a href="#64" class="mim-tip-reference" title="Wollnik, B., Tukel, T., Uyguner, O., Ghanbari, A., Kayserili, H., Emiroglu, M., Yuksel-Apak, M. <strong>Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome.</strong> Am. J. Med. Genet. 122A: 42-45, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12949970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12949970</a>] [<a href="https://doi.org/10.1002/ajmg.a.20260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12949970">Wollnik et al. (2003)</a> described a Turkish family in which both of the parents, who were consanguineous, were heterozygous for a 268T-C transition in the PAX3 gene, resulting in a tyr90-to-his (Y90H) substitution. The daughter was homozygous for the mutation and was determined to have type 3 Waardenburg syndrome (<a href="/entry/148820">148820</a>). Her eyebrows and eyelashes were completely white, the hair was blond, and the irides were blue. The skin was depigmented with spots of normal pigmentation on the upper part of the body. Other findings included relatively large head, small palpebral fissures, increased inner and outer-canthal distances, flexion deformities of wrists, and fingers with ulnar deviation and minimal webs between fingers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12949970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606931 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606931;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004438 OR RCV001375270 OR RCV002274876" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004438, RCV001375270, RCV002274876" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004438...</a>
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<p>In affected members of a family with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), <a href="#27" class="mim-tip-reference" title="Hoth, C. F., Milunsky, A., Lipsky, N., Sheffer, R., Clarren, S. K., Baldwin, C. T. <strong>Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).</strong> Am. J. Hum. Genet. 52: 455-462, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8447316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8447316</a>]" pmid="8447316">Hoth et al. (1993)</a> identified a heterozygous 380G-T transversion in exon 2 of the PAX3 gene, resulting in an arg56-to-leu (R56L) substitution. One of the affected individuals had a meningomyelocele. The family had been reported by <a href="#10" class="mim-tip-reference" title="Carezani-Gavin, M., Clarren, S. K., Steege, T. <strong>Waardenburg syndrome associated with meningomyelocele. (Letter)</strong> Am. J. Med. Genet. 42: 135-136, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1308353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1308353</a>] [<a href="https://doi.org/10.1002/ajmg.1320420127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1308353">Carezani-Gavin et al. (1992)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8447316+1308353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906947 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906947;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Chinese boy with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), <a href="#12" class="mim-tip-reference" title="Chen, H., Jiang, L., Xie, Z., Mei, L., He, C., Hu, Z., Xia, K., Feng, Y. <strong>Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome.</strong> Biochem. Biophys. Res. Commun. 397: 70-74, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20478267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20478267</a>] [<a href="https://doi.org/10.1016/j.bbrc.2010.05.066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20478267">Chen et al. (2010)</a> identified a heterozygous 238C-G transversion in exon 2 of the PAX3 gene, resulting in a his80-to-asp (H80D) substitution in the paired domain. The mutant protein retained an intact homeodomain and transactivation domain. <a href="#65" class="mim-tip-reference" title="Zhang, H., Chen, H., Luo, H., An, J., Sun, L., Mei, L., He, C., Jiang, L., Jiang, W., Xia, K., Li, J.-D., Feng, Y. <strong>Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.</strong> Hum. Genet. 131: 491-503, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21965087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21965087</a>] [<a href="https://doi.org/10.1007/s00439-011-1098-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21965087">Zhang et al. (2012)</a> performed in vitro functional expression studies in human cells, which showed that the H80D mutant protein was expressed and localized to the nucleus, but caused a dramatically reduced activation of MITF (<a href="/entry/156845">156845</a>) compared to wildtype PAX3. There was no dominant-negative effect of the mutant protein, and the mutant protein could still interact with SOX10 (<a href="/entry/602229">602229</a>), although it did not enhance the activity of SOX10 as much as wildtype. The findings were consistent with haploinsufficiency as a pathogenic mechanism. The patient had bilateral profound hearing loss, unilateral heterochromia irides, and dystopia canthorum. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21965087+20478267" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1559316542 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1559316542;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1559316542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1559316542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023561</a>
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<p>In a Chinese boy with Waardenburg syndrome type 1 (<a href="/entry/193500">193500</a>), <a href="#12" class="mim-tip-reference" title="Chen, H., Jiang, L., Xie, Z., Mei, L., He, C., Hu, Z., Xia, K., Feng, Y. <strong>Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome.</strong> Biochem. Biophys. Res. Commun. 397: 70-74, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20478267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20478267</a>] [<a href="https://doi.org/10.1016/j.bbrc.2010.05.066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20478267">Chen et al. (2010)</a> identified a heterozygous 1-bp deletion (556delC) in exon 4 of the PAX3 gene, resulting in a frameshift at premature termination at residue 192 (His186fsTer5). The mutant protein would lack the homeodomain and transactivation domain. <a href="#65" class="mim-tip-reference" title="Zhang, H., Chen, H., Luo, H., An, J., Sun, L., Mei, L., He, C., Jiang, L., Jiang, W., Xia, K., Li, J.-D., Feng, Y. <strong>Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.</strong> Hum. Genet. 131: 491-503, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21965087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21965087</a>] [<a href="https://doi.org/10.1007/s00439-011-1098-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21965087">Zhang et al. (2012)</a> performed in vitro functional expression studies in human cells, which showed that the truncated protein was expressed and localized to both the nucleus and cytoplasm, but failed to activate MITF (<a href="/entry/156845">156845</a>). There was no dominant-negative effect of the mutant protein, consistent with haploinsufficiency as a pathogenic mechanism. The mutant protein was still able to interact with SOX10 (<a href="/entry/602229">602229</a>), but did not enhance its activity. The patient had bilateral profound hearing loss, bilateral heterochromia irides, and dystopia canthorum. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21965087+20478267" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Pilz1993" class="mim-tip-reference" title="Pilz, A. J., Povey, S., Gruss, P., Abbott, C. M. <strong>Mapping of the human homologs of the murine paired-box-containing genes.</strong> Mammalian Genome 4: 78-82, 1993.">Pilz et al. (1993)</a>; <a href="#Wilcox1992" class="mim-tip-reference" title="Wilcox, E. R., Rivolta, M. N., Ploplis, B., Potterf, S. B., Fex, J. <strong>The PAX3 gene is mapped to human chromosome 2 together with a highly informative CA dinucleotide repeat.</strong> Hum. Molec. Genet. 1: 215, 1992.">Wilcox et al. (1992)</a>
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Asher, J. H., Jr., Harrison, R. W., Morell, R., Carey, M. L., Friedman, T. B.
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<strong>Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: a murine model of Waardenburg syndrome variation.</strong>
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Genomics 34: 285-298, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8786127" 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/10.1006/geno.1996.0289" target="_blank">Full Text</a>]
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<strong>Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome.</strong>
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Hum. Mutat. 7: 30-35, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8664898" 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/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T" target="_blank">Full Text</a>]
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<strong>An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.</strong>
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Nature 355: 637-638, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1347149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Baldwin, C. T., Hoth, C. F., Macina, R. A., Milunsky, A.
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<strong>Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and review of the literature.</strong>
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Am. J. Med. Genet. 58: 115-122, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533800" 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.1320580205" target="_blank">Full Text</a>]
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<strong>PAX3 gene structure, alternative splicing and evolution.</strong>
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Gene 237: 311-319, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0378-1119(99)00339-x" target="_blank">Full Text</a>]
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<a id="Barr1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barr, F. G., Galili, N., Holick, J., Biegel, J. A., Rovera, G., Emanuel, B. S.
|
|
<strong>Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma.</strong>
|
|
Nature Genet. 3: 113-117, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8098985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8098985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8098985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0293-113" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bondurand2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bondurand, N., Pingault, V., Goerich, D. E., Lemort, N., Sock, E., Le Caignec, C., Wegner, M., Goossens, M.
|
|
<strong>Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome.</strong>
|
|
Hum. Molec. Genet. 9: 1907-1917, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942418</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.13.1907" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Bosher1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bosher, S. K., Hallpike, C. S.
|
|
<strong>Observations on the histogenesis of the inner ear degeneration of the deaf white cat and its possible relationship to the aetiology of certain unexplained varieties of human congenital deafness.</strong>
|
|
J. Laryng. 80: 222-235, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5907833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5907833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5907833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1017/s0022215100065191" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Burri1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G., Noll, M.
|
|
<strong>Conservation of the paired domain in metazoans and its structure in three isolated human genes.</strong>
|
|
EMBO J. 8: 1183-1190, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2501086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2501086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2501086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03490.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Carezani-Gavin1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carezani-Gavin, M., Clarren, S. K., Steege, T.
|
|
<strong>Waardenburg syndrome associated with meningomyelocele. (Letter)</strong>
|
|
Am. J. Med. Genet. 42: 135-136, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1308353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1308353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1308353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320420127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Chatkupt1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chatkupt, S., Chatkupt, S., Johnson, W. G.
|
|
<strong>Waardenburg syndrome and myelomeningocele in a family.</strong>
|
|
J. Med. Genet. 30: 83-84, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8423616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8423616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8423616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.30.1.83" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Chen2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, H., Jiang, L., Xie, Z., Mei, L., He, C., Hu, Z., Xia, K., Feng, Y.
|
|
<strong>Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome.</strong>
|
|
Biochem. Biophys. Res. Commun. 397: 70-74, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20478267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20478267</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20478267" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.bbrc.2010.05.066" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="da-Silva1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
da-Silva, E. O.
|
|
<strong>Waardenburg I syndrome: a clinical and genetic study of two large Brazilian kindreds, and literature review.</strong>
|
|
Am. J. Med. Genet. 40: 65-74, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1887852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1887852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1887852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320400113" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="de Morree2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Morree, A., Klein, J. D. D., Gan, Q., Farup, J., Urtasun, A., Kanugovi, A., Bilen, B., van Velthoven, C. T. J., Quarta, M., Rando, T. A.
|
|
<strong>Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function.</strong>
|
|
Science 366: 734-738, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31699935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31699935</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31699935[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=31699935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.aax1694" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Epstein1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Epstein, D. J., Malo, D., Vekemans, M., Gros, P.
|
|
<strong>Molecular characterization of a deletion encompassing the Splotch mutation on mouse chromosome 1.</strong>
|
|
Genomics 10: 89-93, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2045114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2045114</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2045114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90488-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Epstein1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Epstein, D. J., Vekemans, M., Gros, P.
|
|
<strong>Splotch (Sp-2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3.</strong>
|
|
Cell 67: 767-774, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1682057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1682057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1682057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(91)90071-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Epstein1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Epstein, D. J., Vogan, K. J., Trasler, D. G., Gros, P.
|
|
<strong>A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the Splotch (Sp) mouse mutant.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 532-536, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8421686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8421686</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8421686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.90.2.532" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Farrer1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Farrer, L. A., Arnos, K. S., Asher, J. H., Jr., Baldwin, C. T., Diehl, S. R., Friedman, T. B., Greenberg, J., Grundfast, K. M., Hoth, C., Lalwani, A. K., Landa, B., Leverton, K., Milunsky, A., Morell, R., Nance, W. E., Newton, V., Ramesar, R., Rao, V. S., Reynolds, J. E., San Agustin, T. B., Wilcox, E. R., Winship, I., Read, A. P.
|
|
<strong>Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes.</strong>
|
|
Am. J. Hum. Genet. 55: 728-737, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7942851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7942851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7942851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Fleming2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fleming, A., Copp, A. J.
|
|
<strong>A genetic risk factor for mouse neural tube defects: defining the embryonic basis.</strong>
|
|
Hum. Molec. Genet. 9: 575-581, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.4.575" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Fortin1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fortin, A. S., Underhill, D. A., Gros, P.
|
|
<strong>Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain.</strong>
|
|
Hum. Molec. Genet. 6: 1781-1790, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302254</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302254" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/6.11.1781" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Fredericks1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fredericks, W. J., Galili, N., Mukhopadhyay, S., Rovera, G., Bennicelli, J., Barr, F. G., Rauscher, F. J., III.
|
|
<strong>The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3.</strong>
|
|
Molec. Cell. Biol. 15: 1522-1535, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7862145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7862145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7862145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.15.3.1522" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Galili1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Galili, N., Davis, R. J., Fredericks, W. J., Mukhopadhyay, S., Rauscher, F. J., III, Emanuel, B. S., Rovera, G., Barr, F. G.
|
|
<strong>Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma.</strong>
|
|
Nature Genet. 5: 230-235, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8275086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1193-230" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Ganguly1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ganguly, A., Rock, M. J., Prockop, D. J.
|
|
<strong>Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 10325-10329, 1993. Note: Erratum: Proc. Nat. Acad. Sci. 91: 5217 only, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8234293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8234293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8234293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.90.21.10325" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Goodman1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goodman, R. M., Lewithal, I., Solomon, A., Klein, D.
|
|
<strong>Upper limb involvement in the Klein-Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 11: 425-433, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7091186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7091186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7091186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320110407" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Goulding1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goulding, M. D., Chalepakis, G., Deutsch, U., Erselius, J. R., Gruss, P.
|
|
<strong>Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.</strong>
|
|
EMBO J. 10: 1135-1147, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1991.tb08054.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Hol1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hol, F. A., Hamel, B. C. J., Geurds, M. P. A., Mullaart, R. A., Barr, F. G., Macina, R. A., Mariman, E. C. M.
|
|
<strong>A frameshift mutation in the gene for PAX3 in a girl with spina bifida and mild signs of Waardenburg syndrome.</strong>
|
|
J. Med. Genet. 32: 52-56, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7897628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7897628</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7897628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.32.1.52" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Hoth1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoth, C. F., Milunsky, A., Lipsky, N., Sheffer, R., Clarren, S. K., Baldwin, C. T.
|
|
<strong>Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).</strong>
|
|
Am. J. Hum. Genet. 52: 455-462, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8447316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8447316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8447316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Ishikiriyama1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ishikiriyama, S., Tonoki, H., Shibuya, Y., Chin, S., Harada, N., Abe, K., Niikawa, N.
|
|
<strong>Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3).</strong>
|
|
Am. J. Med. Genet. 33: 505-507, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2596512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2596512</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2596512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320330419" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Ishikiriyama1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ishikiriyama, S.
|
|
<strong>Gene for Waardenburg syndrome type I is located at 2q35, not at 2q37.3. (Letter)</strong>
|
|
Am. J. Med. Genet. 46: 608, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8322830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8322830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8322830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320460534" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Jacobs-Cohen1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jacobs-Cohen, R. J., Payette, R. F., Gershon, M. D., Rothman, T. P.
|
|
<strong>Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive environment.</strong>
|
|
J. Comp. Neurol. 255: 425-438, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3819023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3819023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3819023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/cne.902550309" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Khan1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Khan, J., Bittner, M. L., Saal, L. H., Teichmann, U., Azorsa, D. O., Gooden, G. C., Pavan, W. J., Trent, J. M., Meltzer, P. S.
|
|
<strong>cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 13264-13269, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10557309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10557309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10557309[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=10557309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.23.13264" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Lagutina2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lagutina, I., Conway, S. J., Sublett, J., Grosveld, G. C.
|
|
<strong>Pax3-FKHR knock-in mice show developmental aberrations but do not develop tumors.</strong>
|
|
Molec. Cell. Biol. 22: 7204-7216, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12242297[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=12242297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.22.20.7204-7216.2002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Lang2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lang, D., Epstein, J. A.
|
|
<strong>Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer.</strong>
|
|
Hum. Molec. Genet. 12: 937-945, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg107" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Lang2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lang, D., Lu, M. M., Huang, L., Engelka, K. A., Zhang, M., Chu, E. Y., Lipner, S., Skoultchi, A., Millar, S. E., Epstein, J. A.
|
|
<strong>Pax3 functions at a nodal point in melanocyte stem cell differentiation.</strong>
|
|
Nature 433: 884-887, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15729346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15729346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15729346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature03292" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Macina1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Macina, R. A., Barr, F. G., Galili, N., Riethman, H. C.
|
|
<strong>Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma.</strong>
|
|
Genomics 26: 1-8, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7782066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7782066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7782066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(95)80076-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Milunsky1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Milunsky, A., Lipsky, N., Sheffer, R., Zlotogora, J., Baldwin, C.
|
|
<strong>A mutation in the Waardenburg syndrome (WS-I) gene in a family with 'WS-III'. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A222, 1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Milunsky1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Milunsky, A.
|
|
<strong>Personal Communication.</strong>
|
|
Boston, Mass. 3/4/1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Moase1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moase, C. E., Trasler, D. G.
|
|
<strong>Splotch locus mouse mutants: models for neural tube defects and Waardenburg syndrome type I in humans.</strong>
|
|
J. Med. Genet. 29: 145-151, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1552554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1552554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1552554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.29.3.145" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Morell1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morell, R., Friedman, T. B., Moeljopawiro, S., Hartono, (NI), Soewito, (NI), Asher, J. H., Jr.
|
|
<strong>A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.</strong>
|
|
Hum. Molec. Genet. 1: 243-247, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303193</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303193" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/1.4.243" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Motohashi1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Motohashi, H., Hozawa, K., Oshima, T., Takeuchi, T., Takasaka, T.
|
|
<strong>Dysgenesis of melanocytes and cochlear dysfunction in mutant microphthalmia (mi) mice.</strong>
|
|
Hear. Res. 80: 10-20, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7852195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7852195</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7852195" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0378-5955(94)90003-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Newton1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., Markham, A. F.
|
|
<strong>Analysis of any point mutation in DNA: the amplification refractory mutation system (ARMS).</strong>
|
|
Nucleic Acids Res. 17: 2503-2516, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2785681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2785681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2785681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/17.7.2503" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Pilz1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pilz, A. J., Povey, S., Gruss, P., Abbott, C. M.
|
|
<strong>Mapping of the human homologs of the murine paired-box-containing genes.</strong>
|
|
Mammalian Genome 4: 78-82, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8431641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8431641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8431641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00290430" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Pritchard2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pritchard, C., Grosveld, G., Hollenbach, A. D.
|
|
<strong>Alternative splicing of Pax3 produces a transcriptionally inactive protein.</strong>
|
|
Gene 305: 61-69, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12594042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12594042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12594042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0378-1119(02)01186-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Relaix2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Relaix, F., Polimeni, M., Rocancourt, D., Ponzetto, C., Schafer, B. W., Buckingham, M.
|
|
<strong>The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo.</strong>
|
|
Genes Dev. 17: 2950-2965, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14665670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14665670</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14665670[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=14665670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.281203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Relaix2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Relaix, F., Rocancourt, D., Mansouri, A., Buckingham, M.
|
|
<strong>A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. (Letter)</strong>
|
|
Nature 435: 948-953, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature03594" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Reynolds1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reynolds, J. E., Meyer, J. M., Landa, B., Stevens, C. A., Arnos, K. S., Israel, J., Marazita, M. L., Bodurtha, J., Nance, W. E., Diehl, S. R.
|
|
<strong>Analysis of variability of clinical manifestations in Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 57: 540-547, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320570405" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Ridgeway2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ridgeway, A. G., Skerjanc, I. S.
|
|
<strong>Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2.</strong>
|
|
J. Biol. Chem. 276: 19033-19039, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11262400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11262400</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11262400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M011491200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Roeb2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roeb, W., Boyer, A., Cavenee, W. K., Arden, K. C.
|
|
<strong>PAX3-FOXO1 controls expression of the p57Kip2 cell-cycle regulator through degradation of EGR1.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 18085-18090, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17986608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17986608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17986608[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=17986608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0708910104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Scheidler1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scheidler, S., Fredericks, W. J., Rauscher, F. J., III, Barr, F. G., Vogt, P. K.
|
|
<strong>The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 9805-9809, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790412</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.93.18.9805" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Sheffer1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sheffer, R., Zlotogora, J.
|
|
<strong>Autosomal dominant inheritance of Klein-Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 42: 320-322, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1536170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1536170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1536170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320420312" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Sommer1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sommer, A., Young-Wee, T., Frye, T.
|
|
<strong>Previously undescribed syndrome of craniofacial, hand anomalies, and sensorineural deafness.</strong>
|
|
Am. J. Med. Genet. 15: 71-77, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6859126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6859126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6859126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320150109" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Steel1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Steel, K. P., Smith, R. J. H.
|
|
<strong>Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1.</strong>
|
|
Nature Genet. 2: 75-79, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303254</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303254" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0992-75" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Sublett1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sublett, J. E., Jeon, I-S., Shapiro, D. N.
|
|
<strong>The alveolar rhabdomyosarcoma PAX3/FKHR fusion protein is a transcriptional activator.</strong>
|
|
Oncogene 11: 545-552, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7630639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7630639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7630639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Tachibana1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tachibana, M., Takeda, K., Nobukuni, Y., Urabe, K., Long, J. E., Meyers, K. A., Aaronson, S. A., Miki, T.
|
|
<strong>Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocytes characteristics.</strong>
|
|
Nature Genet. 14: 50-54, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782819</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8782819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0996-50" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Tassabehji1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tassabehji, M., Newton, V. E., Liu, X.-Z., Brady, A., Donnai, D., Krajewska-Walasek, M., Murday, V., Norman, A., Obersztyn, E., Reardon, W., Rice, J. C., Trembath, R., Wieacker, P., Whiteford, M., Winter, R., Read, A. P.
|
|
<strong>The mutational spectrum in Waardenburg syndrome.</strong>
|
|
Hum. Molec. Genet. 4: 2131-2137, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.11.2131" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Tassabehji1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tassabehji, M., Read, A. P., Newton, V. E., Harris, R., Balling, R., Gruss, P., Strachan, T.
|
|
<strong>Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.</strong>
|
|
Nature 355: 635-636, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347148</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1347148" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/355635a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Tassabehji1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T.
|
|
<strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong>
|
|
Nature Genet. 3: 26-30, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0193-26" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
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<a id="Tekin2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tekin, M., Bodurtha, J. N., Nance, W. E., Pandya, A.
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<strong>Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome?</strong>
|
|
Clin. Genet. 60: 301-304, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11683776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11683776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11683776" 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/10.1034/j.1399-0004.2001.600408.x" target="_blank">Full Text</a>]
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</p>
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<a id="59" class="mim-anchor"></a>
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<a id="Tsukamoto1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tsukamoto, K., Nakamura, Y., Niikawa, N.
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<strong>Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues.</strong>
|
|
Hum. Genet. 93: 270-274, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545913</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00212021" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="60" class="mim-anchor"></a>
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<a id="Tsukamoto1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tsukamoto, K., Tohma, T., Ohta, T., Yamakawa, K., Fukushima, Y., Nakamura, Y., Niikawa, N.
|
|
<strong>Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I.</strong>
|
|
Hum. Molec. Genet. 1: 315-317, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303207" 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/1.5.315" target="_blank">Full Text</a>]
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<li>
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<a id="61" class="mim-anchor"></a>
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<a id="Watanabe1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watanabe, A., Takeda, K., Ploplis, B., Tachibana, M.
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<strong>Epistatic relationship between Waardenburg syndrome genes MITF and PAX3.</strong>
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|
Nature Genet. 18: 283-286, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9500554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9500554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9500554" 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/ng0398-283" target="_blank">Full Text</a>]
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<a id="62" class="mim-anchor"></a>
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<a id="Wilcox1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wilcox, E. R., Rivolta, M. N., Ploplis, B., Potterf, S. B., Fex, J.
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<strong>The PAX3 gene is mapped to human chromosome 2 together with a highly informative CA dinucleotide repeat.</strong>
|
|
Hum. Molec. Genet. 1: 215, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303187</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303187" 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/1.3.215-a" target="_blank">Full Text</a>]
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<a id="Wildhardt1996" class="mim-anchor"></a>
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<p class="mim-text-font">
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Wildhardt, G., Winterpacht, A., Hibert, K., Menger, H., Zabel, B.
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<strong>Two different PAX3 gene mutations causing Waardenburg syndrome type I.</strong>
|
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Molec. Cell. Probes 10: 229-231, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8799378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8799378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8799378" 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/10.1006/mcpr.1996.0032" target="_blank">Full Text</a>]
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<a id="Wollnik2003" class="mim-anchor"></a>
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Wollnik, B., Tukel, T., Uyguner, O., Ghanbari, A., Kayserili, H., Emiroglu, M., Yuksel-Apak, M.
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<strong>Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome.</strong>
|
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Am. J. Med. Genet. 122A: 42-45, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12949970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12949970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12949970" 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.20260" target="_blank">Full Text</a>]
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<a id="65" class="mim-anchor"></a>
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<a id="Zhang2012" class="mim-anchor"></a>
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Zhang, H., Chen, H., Luo, H., An, J., Sun, L., Mei, L., He, C., Jiang, L., Jiang, W., Xia, K., Li, J.-D., Feng, Y.
|
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<strong>Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.</strong>
|
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Hum. Genet. 131: 491-503, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21965087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21965087</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21965087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-011-1098-2" target="_blank">Full Text</a>]
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<li>
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<a id="66" class="mim-anchor"></a>
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<a id="Zlotogora1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zlotogora, J., Lerer, I., Bar-David, S., Ergaz, Z., Abeliovich, D.
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<strong>Homozygosity for Waardenburg syndrome.</strong>
|
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Am. J. Hum. Genet. 56: 1173-1178, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 12/11/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/26/2012<br>Cassandra L. Kniffin - updated : 3/8/2010<br>Patricia A. Hartz - updated : 4/9/2008<br>Ada Hamosh - updated : 2/10/2006<br>Ada Hamosh - updated : 9/7/2005<br>George E. Tiller - updated : 2/21/2005<br>Patricia A. Hartz - updated : 1/9/2004<br>Victor A. McKusick - updated : 9/25/2003<br>Patricia A. Hartz - updated : 4/1/2003
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</span>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 1/7/2002
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/11/2023
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 05/04/2022<br>alopez : 12/11/2019<br>alopez : 08/09/2016<br>carol : 08/04/2016<br>carol : 10/01/2013<br>carol : 9/19/2013<br>terry : 3/15/2013<br>terry : 11/13/2012<br>alopez : 4/3/2012<br>alopez : 4/3/2012<br>alopez : 4/3/2012<br>terry : 3/28/2012<br>ckniffin : 3/26/2012<br>carol : 3/11/2010<br>ckniffin : 3/8/2010<br>mgross : 4/10/2008<br>mgross : 4/10/2008<br>terry : 4/9/2008<br>alopez : 2/17/2006<br>terry : 2/10/2006<br>alopez : 9/14/2005<br>terry : 9/7/2005<br>wwang : 3/2/2005<br>wwang : 3/2/2005<br>terry : 2/21/2005<br>mgross : 1/9/2004<br>carol : 11/5/2003<br>tkritzer : 10/14/2003<br>cwells : 9/25/2003<br>mgross : 4/7/2003<br>mgross : 4/7/2003<br>terry : 4/1/2003<br>ckniffin : 8/26/2002<br>carol : 7/8/2002<br>ckniffin : 5/15/2002<br>carol : 1/8/2002<br>carol : 1/8/2002
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</span>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606597
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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PAIRED BOX GENE 3; PAX3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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PAIRED DOMAIN GENE HuP2; HUP2
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<p>
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<span class="h3 mim-font">
|
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PAX3/FKHR FUSION GENE, INCLUDED
|
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: PAX3</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1010606009, 237918004, 702362004;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 2q36.1
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:222,199,887-222,298,998 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
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|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
2q36.1
|
|
</span>
|
|
</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Craniofacial-deafness-hand syndrome
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
122880
|
|
</span>
|
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Rhabdomyosarcoma 2, alveolar
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</span>
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</td>
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<td>
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<span class="mim-font">
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268220
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</span>
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</td>
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<td>
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<span class="mim-font">
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Somatic mutation
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Waardenburg syndrome, type 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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193500
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Waardenburg syndrome, type 3
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</span>
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</td>
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<td>
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<span class="mim-font">
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148820
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Based on amino acid sequence homology and common genomic exon/intron organization (Goulding et al., 1991), Burri et al. (1989) suggested that the human homolog of the mouse Pax3 gene is the HUP2 gene. Goulding et al. (1991) found that the product of the mouse Pax3 gene is a DNA-binding protein expressed during early neurogenesis. The HuP2 sequence contains 3 exons, which Tassabehji et al. (1992) designated exons 2, 3, and 4 because of their correspondence with exons 2, 3, and 4 of the mouse Pax3 gene, which has 5 exons. Tassabehji et al. (1992) found that the HuP2 sequence showed 92% nucleotide homology and 100% amino acid homology with the mouse Pax3 sequence over amino acids 2 to 121. </p><p>Tsukamoto et al. (1994) cloned PAX3 by 5-prime and 3-prime RACE of an adult cerebellum cDNA library. They identified 2 alternatively spliced isoforms, which they called PAX3A and PAX3B. The deduced PAX3A and PAX3B transcription factors contain 215 and 206 amino acids, respectively. RT-PCR detected high PAX3B expression in esophagus and stomach, with moderate levels in cerebellum, liver, and pancreas. PAX3B was not detected in lung, ovary, uterus, and cardiac muscle. PAX3A was expressed only in cerebellum, esophagus, and skeletal muscle. </p><p>Barber et al. (1999) cloned PAX3 from a skeletal muscle cDNA library. They also cloned mouse Pax3. Barber et al. (1999) identified several alternatively spliced isoforms in adult skeletal muscle and in mouse embryos, including 1 that shares significant evolutionary conservation between quail, mouse, and human. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Macina et al. (1995) determined that the PAX3 gene contains 8 exons and spans more than 100 kb. Analysis of the intronic translocation breakpoint region associated with alveolar rhabdomyosarcoma (268220) revealed a pair of inverted Alu repeats and a pair of inverted (GT)n-rich microsatellite repeats. The 5-prime region contains a microsatellite, putative CAAT, TATA, and CAP sites, and several binding sites for AP1 (see 165160) and SP1 (189906). </p><p>Barber et al. (1999) determined that the PAX3 gene contains 10 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By analysis of an inversion breakpoint associated with Waardenburg syndrome type 1 (WS1; 193500), Tsukamoto et al. (1992) and Ishikiriyama (1993) mapped the PAX3 gene to chromosome 2q35. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bondurand et al. (2000) showed that SOX10 (602229), in synergy with PAX3, strongly activates MITF (156845) expression in transfection assays. Transfection experiments revealed that PAX3 and SOX10 interact directly by binding to a proximal region of the MITF promoter containing binding sites for both factors. Mutant SOX10 or PAX3 proteins failed to transactivate this promoter, providing further evidence that the 2 genes act in concert to directly regulate expression of MITF. In situ hybridization experiments carried out in the dominant megacolon (Dom) mouse confirmed that SOX10 dysfunction impaired Mitf expression as well as melanocytic development and survival. The authors hypothesized that interaction between 3 of the genes that are altered in Waardenburg syndrome (see 193500) could explain the auditory/pigmentary symptoms of this disease. </p><p>Mutations in the MITF and PAX3 genes, encoding transcriptions factors, are responsible for Waardenburg syndrome 2A (WS2A; 193510) and WS1 (193500)/WS3 (148820), respectively. Tachibana et al. (1996) showed that MITF transactivates the gene for tyrosinase (see 606933), a key enzyme for melanogenesis, and is critically involved in melanocyte differentiation. Absence of melanocytes affects pigmentation in the skin, hair, and eyes, and hearing function in the cochlea. Therefore, hypopigmentation and hearing loss in WS2A are likely to be the results of an anomaly of melanocyte differentiation caused by MITF mutations. Watanabe et al. (1998) showed that PAX3 transactivates the MITF promoter. They further showed that PAX3 proteins associated with WS1 in either the paired domain or the homeodomain failed the recognize and transactivate the MITF promoter. These results provided evidence that PAX3 directly regulates MITF, and suggested that the failure of this regulation due to PAX3 mutations causes the auditory-pigmentary symptoms in at least some individuals with WS1. </p><p>Ridgeway and Skerjanc (2001) showed that expression of Pax3 induced myogenesis in a mouse pluripotent stem cell line. Pax3 induced expression of the transcription factor Six1 (601205), its cofactor Eya2 (601654), and the transcription factor Mox1 (600147), prior to inducing expression of MyoD (159970) and myogenin (159980). Expression of dominant-negative Pax3 resulted in loss of expression of Six1, Eya2, and endogenous Pax3, as well as downregulation of Mox1 expression. Pax3 expression had no effect on cardiogenesis in this cell line. Ridgeway and Skerjanc (2001) concluded that Pax3 controls a cascade of transcriptional events that are necessary and sufficient for skeletal myogenesis. </p><p>The Sox10 and Pax3 transcription factors can directly regulate both MITF and RET (164761) in a synergistic fashion. Lang and Epstein (2003) showed that Pax3 and Sox10 can physically interact; this interaction contributes to synergistic activation of a conserved RET enhancer, and it explains why Sox10 mutants that cannot bind DNA still retain the ability to activate this enhancer in the presence of Pax3. However, in the context of the MITF gene, Pax3 and Sox10 must each bind independently to DNA in order to achieve synergy. These observations appear to explain the phenotype in the mild form of Yemenite deaf-blind syndrome caused by a specific SOX10 mutation (602229.0005) in the HMG box that abrogates DNA binding without disrupting association with PAX3. </p><p>Pritchard et al. (2003) identified an alternatively spliced isoform of mouse Pax3 produced by skipping exon 8. Deletion of exon 8 removes most of the Pax3 transcriptional activation domain. Pritchard et al. (2003) demonstrated that this isoform is transcriptionally inactive, but it can inhibit the activity of the full-length protein. </p><p>Relaix et al. (2005) identified a new cell population that expresses the transcription factors Pax3 and Pax7 (167410) but no skeletal muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, Relaix et al. (2005) demonstrated that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a nonmyogenic fate. Relaix et al. (2005) concluded that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation. </p><p>Lang et al. (2005) described the molecular details of a nodal point in adult melanocyte stem cell differentiation in which PAX3 simultaneously functions to initiate a melanogenic cascade while acting downstream to prevent terminal differentiation. PAX3 activates expression of MITF and at the same time competes with MITF for occupancy of an enhancer required for expression of dopachrome tautomerase (191275), an enzyme that functions in melanin synthesis. PAX3-expressing melanoblasts are thus committed but undifferentiated until PAX3-mediated repression is relieved by activated beta-catenin (see 116806). Lang et al. (2005) concluded that a stem cell transcription factor can both determine cell fate and simultaneously maintain an undifferentiated state, leaving a cell poised to differentiate in response to external stimuli. </p><p>In mice, de Morree et al. (2019) demonstrated that variation in muscle stem cell activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. De Morree et al. (2019) showed that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1 (SNRNP70; 180740). Isoforms of the Pax3 mRNA that differed in their 3-prime UTRs were differentially susceptible to regulation by microRNA miR206 (611599), which resulted in varying levels of the Pax3 protein in vivo. De Morree et al. (2019) concluded that their findings highlighted a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species. </p><p><strong><em>PAX3/FKHR Fusion Protein</em></strong></p><p>
|
|
Fredericks et al. (1995) demonstrated expression of a 97-kD PAX3/FKHR (FOXO1A; 136533) fusion protein in a t(2;13)-positive rhabdomyosarcoma cell line (see CYTOGENETICS section) and verified that a single polypeptide contained epitopes derived from each protein. The fusion protein was localized to the nucleus in these cells, as was wildtype PAX3 in cells lacking the translocation. They found that DNA binding of the fusion protein was significantly impaired relative to that of PAX3 despite the fact that the 2 proteins had identical PAX DNA-binding domains. However, the fusion protein was a much more potent transcriptional activator than PAX3. Thus, the fusion protein may function as an oncogenic transcription factor by enhancing activation of normal PAX3 target genes. </p><p>Sublett et al. (1995) found that the PAX3/FKHR hybrid protein binds DNA in vitro in a sequence-specific manner and transactivates the expression of artificial reporter genes, suggesting that its aberrant expression could subvert the transcriptional programs that normally control the growth, differentiation, and survival of primitive myogenic precursors in vivo. </p><p>Using a retroviral vector, Scheidler et al. (1996) introduced the PAX3/FKHR fusion gene into chicken embryo fibroblasts. Expression of the PAX3/FKHR protein in these cells led to transformation: the cells became enlarged, grew tightly packed and in multiple layers, and acquired the ability for anchorage-independent growth. </p><p>The PAX3/FKHR chimeric gene possesses transforming properties. To investigate the actions of these transcription factors, Khan et al. (1999) introduced both PAX3 and PAX3/FKHR into NIH 3T3 cells, and the resultant gene expression changes were analyzed with a mouse cDNA microarray containing 2,225 elements. They found that PAX3/FKHR but not PAX3 activated a myogenic transcription program including the induction of transcription factors Myod (159970), myogenin (159980), Six1 (601205), and Slug (602150), as well as a battery of genes involved in several aspects of muscle function. </p><p>Roeb et al. (2007) found that myoblasts from transgenic mice expressing PAX3/FOXO1 under control of the PAX3 promoter were unable to complete myogenic differentiation because of an inability to upregulate p57(Kip2) (CDKN1C; 600856) transcription. This defect was caused by reduced levels of the transcriptional activator Egr1 (128990) resulting from a direct, destabilizing interaction with PAX3/FOXO1. Neither PAX3 nor FOXO1 shared the ability to regulate p57(Kip2) transcription. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Tsukamoto et al. (1992) cloned and characterized an inversion breakpoint of the inv(2)(q35q37.3) paracentric inversion reported by Ishikiriyama et al. (1989) in a child with Waardenburg syndrome type 1. Genomic cosmid clones containing the HUP2 gene were isolated from a library constructed from the patient's DNA. One of the clones contained the inversion breakpoint and revealed signals at both 2q35 and 2q37 by fluorescence in situ hybridization, indicating that the HUP2 gene had been disrupted by the inversion. The results suggested that the gene is situated at the more proximal breakpoint 2q35 because one cosmid clone, presumably derived from the normal allele, hybridized only to 2q35. </p><p><strong><em>PAX3/FKHR Fusion Gene</em></strong></p><p>
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|
A frequent finding in alveolar rhabdomyosarcomas is the translocation t(2;13)(q35;q14). Barr et al. (1993) determined that the PAX3 gene is affected by the t(2;13) translocation associated with alveolar rhabdomyosarcoma. The rearrangement breakpoints occurred within an intron downstream of the paired box and homeodomain-encoding regions. Galili et al. (1993) isolated the chromosome 13 gene that is fused with PAX3 and identified it as a member of the forkhead domain family, which encodes transcription factors containing a conserved DNA-binding motif related to the Drosophila region-specific homeotic gene 'forkhead.' They referred to the gene as FKHR (FOXO1A; 136533) for 'forkhead in rhabdomyosarcoma.' Thus, disruption of the PAX3 gene can cause either neoplasia or congenital malformation. Other genes that are implicated in both neoplasia and congenital anomalies include the oncogene GLI3 (165240), the oncogene RET (164761), and the tumor suppressor gene WT1 (607102). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Tassabehji et al. (1992) identified variations in the PAX3 gene in 6 of 17 unrelated patients with Waardenburg syndrome type 1 (WS1; 193500), using primers to amplify exons followed by testing for heteroduplex formation on polyacrylamide gels. No variants were seen in any exon in 50 normal controls. In 3 families that were tested, the variant was found to be familial in 2 and apparently de novo in the third. The variant bands showed perfect linkage to WS in the families studied. One family was found to have a heterozygous 18-bp deletion in the central region of exon 2, resulting in loss of amino acids 29 to 34 (606597.0001). </p><p>Simultaneously and independently, Baldwin et al. (1992) identified a heterozygous mutation in the HuP2 gene (P50L; 606597.0002) in affected members of a large Brazilian family with Waardenburg syndrome type 1 reported by da-Silva (1991). There were 49 affected persons in 6 generations, and more than 78% of the affected individuals had hearing loss. </p><p>Baldwin et al. (1995) described 10 additional mutations in the PAX3 gene in families with WS type 1. Eight of these mutations were in a region of PAX3 where only 1 mutation had previously been described. Taken together with previously reported mutations, these mutations covered essentially the entire PAX3 gene. All but 1 of the mutations were 'private;' only 1 mutation had been reported in 2 apparently unrelated families. Preliminary screening for mutations was performed with conformation-sensitive gel electrophoresis (CSGE), as described by Ganguly et al. (1993). Baldwin et al. (1995) also cataloged 16 previously reported mutations and 5 chromosomal abnormalities affecting the 2q35 region that were associated with WS. </p><p>Among 24 unrelated individuals with WS1 mutations, Farrer et al. (1994) found that no 2 had the same point mutation in the protein-coding region of PAX3 nor did any of them have a change in the same codon. </p><p>In each of 2 families with WS type 1, Wildhardt et al. (1996) described the causative PAX3 mutation. One mutation was an insertion in the paired box domain resulting in a protein termination within the paired box. The second mutation was a single-basepair substitution producing an arg271-to-cys amino acid change in the homeobox region. </p><p>In the 'Splotch-delayed' mouse, mutation in the Pax3 paired domain (G9R) abrogates the DNA-binding activity of both the paired domain and the homeodomain, suggesting that they may functionally interact. To investigate this possibility further, Fortin et al. (1997) analyzed the DNA binding properties of additional point mutations in the PAX3 paired domain and homeodomain that occur in Waardenburg syndrome patients. Within the paired domain, 7 of 10 mutations were found to abrogate DNA binding by the paired domain. Remarkably, these 7 mutations also affected DNA binding by the homeodomain, causing either a complete loss, a reduction, or an increase in DNA-binding activity. In addition, the effect of paired domain mutations occurred at the level of monomer formation by the homeodomain, while the dimerization potential of this domain seemed unaffected in mutants where it could be analyzed. One mutation in the homeodomain also abrogated DNA binding by the paired domain. The observation that independent mutations in either domain can affect DNA binding by the other in the intact PAX3 protein strongly suggests that the 2 domains are not functionally independent but bind DNA through cooperative interactions. </p><p>Tassabehji et al. (1995) reported the results of screening for mutations in the PAX3 and MITF genes (156845) in 134 families or individuals with auditory-pigmentary syndromes, such as Waardenburg syndrome or probable neural cristopathies. PAX3 mutations were found in 20 of 25 families with definite WS1 and 1 of 2 with WS3 (148820), but in none of 23 with definite type WS2 (see 193510) or 36 with other neural cristopathies. The latter category included 12 with Hirschsprung disease plus pigmentary disturbances (WS4; see 277580). They concluded that about 20% of cases of WS2 are caused by mutations in MITF. </p><p>Zlotogora et al. (1995) reported a large kindred in which many individuals had Waardenburg syndrome type 1 associated with a heterozygous mutation in the PAX3 gene (S84F; 606597.0009). However, there was 1 child, born of consanguineous parents, who had a severe phenotype consistent with WS type 3 (148820): this patient was found to be homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects. Since all Pax3 mutations in mice lead to severe neural tube defects and intrauterine or neonatal death, the survival of the homozygote in this case and the absence of neural tube defects were unexpected. </p><p>In 2 unrelated Chinese patients with Waardenburg syndrome type 1, Chen et al. (2010) identified 2 different heterozygous mutations in the PAX3 gene (606597.0015 and 606597.0016, respectively). Zhang et al. (2012) performed in vitro functional expression studies showed that the mutant proteins had decreased or abolished ability to transactivate the MITF promoter. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The work of Bosher and Hallpike (1966) on an animal analog, deaf white cats, suggested that destruction of the inner ear mechanism occurs in the first days of extrauterine life and was correlated with an inability to regulate properly the constitution of the endolymphatic fluid. The cat, like man, may escape deafness in one or both ears. If more of the factors that lead to retention of hearing were known, deafness might be preventable. </p><p>Motohashi et al. (1994) pointed out that melanocytes are a normal component of the inner ear, including the stria vascularis. There are 3 known mutations in the mouse which lead to a deficiency of melanocytes in mast cells: white dominant spotting (W), Steel (Sl), and microphthalmia (mi). All 3 mutants have a thin stria vascularis, without melanocyte-like intermediate cells, and severe impairment of hearing. Thus, the absence of intermediate cells or melanocytes causes severe hearing loss. The absence of melanin has little influence on hearing acuity because albino mice without melanin have no impairment of hearing. </p><p>Other genes in the 9q34 band have homologs on mouse chromosome 2. In the mouse, the 'lethal-spotted' (ls) mutation, which results not only in spotting but also in failure of the entire ganglia to colonize the gut, is located on chromosome 2. Jacobs-Cohen et al. (1987) found that in lethal spotting piebald (ls/ls) mice, who develop megacolon, the terminal 2 mm of intestine does not become colonized by neural crest cells, resulting in aganglionosis. Neural crest cells transplanted from areas around the neural tube (primary explants) or foregut (secondary explants) did not colonize the terminal portions of the hindgut. These findings suggested that the nonneuronal components are abnormal, preventing migration of normal neural crest derivatives into the bowel wall. </p><p>Epstein et al. (1991) studied a deletion of mouse chromosome 1 that involved the 'splotch' locus. The murine equivalent of the ALPP gene was included in the deletion, thus supporting the notion that 'splotch' is the equivalent of WS1. Furthermore, Epstein et al. (1991) mapped the paired box gene Pax3 to a region near or at the Sp locus on mouse chromosome 1 and found Pax3 to be deleted in mice heterozygous for a splotch allele. In another allelic variant of splotch, they found deletion of 32 nucleotides in the Pax3 mRNA transcript and gene. The deletion was located within the paired homeodomain of Pax3 and was predicted to create a truncated protein as a result of a newly created termination codon at the deletion breakpoint. The splotch mutation is associated in the mouse with spina bifida and exencephaly. The findings were interpreted to indicate that Pax3 plays a key role in normal neural development. Moase and Trasler (1992) reviewed the subject of the splotch locus in mouse mutants. Steel and Smith (1992) found that, unlike individuals with Waardenburg syndrome, the splotch mouse has normal hearing. They suggested that the difference in expression of the genes in the 2 species may result from different parts of the gene being mutated or from modifying influences as yet undefined. </p><p>Epstein et al. (1993) demonstrated that in the original, spontaneously arising Sp allele, a complex mutation in the PAX3 gene had occurred, including an A-to-T transversion at the invariant 3-prime AG splice acceptor of intron 3. This mutation abrogated the normal splicing of intron 3, resulting in the generation of 4 aberrantly spliced mRNA transcripts. Two of the transcripts made use of cryptic 3-prime splice sites within the downstream exon, generating small deletions which disrupted the reading frame of the transcripts. A third aberrant splicing event resulted in the deletion of exon 4, while a fourth retained intron 3. None of these mutations would be expected to result in functional PAX3 proteins. </p><p>Asher et al. (1996) stated that over 50 human PAX3 mutations leading to hearing, craniofacial, limb, and pigmentation anomalies had been identified. Variability in penetrance and expressivity is observed in humans with PAX3 mutations and in mice with 'splotch' mutations. In mice with certain 'splotch' mutations, influence of the genetic background and sex of the individual on penetrance and expressivity is demonstrable. Asher et al. (1996) described a murine model for Waardenburg syndrome variation and concluded that a minimum of 2 genes interact with the 'splotch' mutation to influence the craniofacial features of these mice. One of these genes may be either X-linked or sex-influenced, while the other is autosomal. They stated that these studies in mice may lead to the identification of genes that modify the expression of human PAX3 mutations. </p><p>Fleming and Copp (2000) exploited variations in the normal pattern of cranial neural tube closure (closure 2) among inbred mouse strains. Strains with a more caudal location of cranial neural tube closure (e.g., DBA/2) were relatively resistant to neural tube defects (NTDs), whereas strains with a rostrally positioned closure 2 (e.g., NZW) exhibited increased susceptibility to NTDs. The authors back-crossed the 'splotch' (Sp2H) mutant gene onto both the DBA/2 and NZW backgrounds. After transfer to the DBA/2 background, the frequency of cranial NTDs was reduced significantly in Sp2H homozygotes, confirming a protective effect of caudal closure 2. In contrast, Sp2H homozygotes on the NZW background had a persistently high frequency of cranial NTDs. The frequency of spina bifida was not altered in either backcross, emphasizing the specificity of this genetic effect for cranial neurulation only. The authors concluded that variation in the pattern of cranial neural tube closure is a genetically determined factor influencing susceptibility to cranial NTDs. </p><p>Lagutina et al. (2002) generated mice carrying a Pax3-Fkhr knockin allele. Despite low expression of this allele, heterozygous offspring of Pax3-Fkhr chimeric mice showed developmental abnormalities, including intraventricular septum defects, tricuspid valve insufficiency, and diaphragm defects, which caused congestive heart failure leading to perinatal death. Heterozygotes also displayed malformations of some, but not all, hypaxial muscles. However, neither newborn heterozygous pups nor their chimeric parents showed any signs of malignancy. Lagutina et al. (2002) concluded that the Pax2-Fkhr allele causes lethal developmental defects in knockin mice but is insufficient to cause muscle tumors. </p><p>Relaix et al. (2003) found that mice expressing Pax3/Fkhr displayed developmental defects, including ectopic delamination and inappropriate migration of muscle precursor cells. These events resulted from overexpression of Met (164860), leading to constitutive activation of Met signaling. The gain-of-function phenotype was also characterized by overactivation of MyoD (159970). </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>16 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 WAARDENBURG SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, 18-BP DEL, EX2
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<br />
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SNP: rs1559320436,
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ClinVar: RCV000004425
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a kindred with Waardenburg syndrome type 1 (193500), Tassabehji et al. (1992) demonstrated a heterozygous deletion of 18 bp from the central region of exon 2 of the PAX3 gene. This resulted in loss of amino acids 29 to 34 of the paired domain. The deleted sequence ran between 2 directly repeated GGCCC sequences. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 WAARDENBURG SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, PRO50LEU
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<br />
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SNP: rs104893650,
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ClinVar: RCV000004426
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Brazilian family with Waardenburg syndrome type 1 (193500) reported by da-Silva (1991), Baldwin et al. (1992) identified a heterozygous G-to-A transition 64 bases downstream from the 5-prime end of exon 2. This changed codon CCG (proline) to CTG (leucine) in the sense strand. Amino acid residue 50 was thought to be involved (Milunsky, 1992), thus resulting in a pro50-to-leu (P50L) substitution. Baldwin et al. (1992) noted that there were 49 affected persons in 6 generations, and more than 78% of the affected individuals had hearing loss. All 26 affected members of the family were heterozygous for the mutation, whereas all 34 unaffected members and 50 control subjects were homozygous for the wildtype allele. Baldwin et al. (1992) did not detect the P50L mutation in 17 unrelated WS1 families. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 WAARDENBURG SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, 14-BP DEL, EX2
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<br />
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SNP: rs1559320252,
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ClinVar: RCV000004427
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an Indonesian family with Waardenburg syndrome type 1 (193500), Morell et al. (1992) identified a 14-bp deletion in the paired domain encoded by exon 2 of the PAX3 gene. The frameshift mutation resulted in a premature termination codon in exon 3. The gene product was a truncated protein lacking most of the paired domain and all of the predicted homeodomain. The deletion started with the last 2 nucleotides of codon 158 and extended through codon 162 of the paired box. Morell et al. (1992) discussed whether the phenotypic effects of the mutation are due to haploinsufficiency of the product protein or to a transdominant negative effect. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 WAARDENBURG SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, 1-BP DEL
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<br />
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ClinVar: RCV000004428
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with Waardenburg syndrome type 1 (193500), designated WS.06, Tassabehji et al. (1993) demonstrated a frameshift mutation in the PAX3 gene. The deletion of the last nucleotide in codon 63 in exon 2 led to premature termination, with amino acid residue 75 corresponding to the beginning of exon 3. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 WAARDENBURG SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, 2-BP DEL, 556CA
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<br />
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SNP: rs1559316535,
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ClinVar: RCV000004429, RCV002272009
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with Waardenburg syndrome type 1 (193500), designated WS.11, Tassabehji et al. (1993) demonstrated a 2-bp deletion in exon 4 of the PAX3 gene that removed one of a tandemly repeated pair of CA dinucleotides. The deletion in exon 4 presumably led to premature termination in exon 5, abolishing the homeodomain. In this family and in 2 others, Tassabehji et al. (1993) used the ARMS method, the amplification refractory mutation system (Newton et al., 1989), to confirm that affected family members had the mutation and that no unaffected family member was carrying the alteration. </p><p>This mutation is designated 556delCA based on the sequencing of Hoth et al. (1993) (see also Tassabehji et al., 1995). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 WAARDENBURG SYNDROME, TYPE 1</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, GLY81ALA
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<br />
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SNP: rs121908111, rs587776586,
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ClinVar: RCV000004430, RCV002512755
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>This variant, originally reported as a GLY48ALA substitution by Tassabehji et al. (1993) has been reclassified as a GLY81ALA substitution based on the sequencing of Hoth et al. (1993) (see Tassabehji et al., 1995). </p><p>Tassabehji et al. (1993) found a GGC-to-GCC transversion in the PAX3 gene, resulting in a gly-to-ala substitution, in a family (WS.15) presumed to have Waardenburg syndrome type 2 (193510) with normal inner canthal distance. However, although 1 individual by measurement said to have an inner canthal distance at the 65th percentile, the photograph (their Figure 4) certainly suggested dystopia canthorum. The affected individual I-2 had a W index of 2.21 but was the only member of the family with a value over 2.07, which is the threshold recommended by the Waardenburg Consortium. The family reported by Tassabehji et al. (1993) was later considered by Tassabehji et al. (1995) to have Waardenburg syndrome type 1 (193500). </p><p>Reynolds et al. (1995) reviewed a collection of 26 WS1 and 8 WS2 families and concluded that the W-index as a means of discriminating between affected WS1 and WS2 individuals 'may be problematic' because (1) ranges of W-index scores of affected and unaffected individuals overlapped considerably within both WS1 and WS2 families, and (2) a considerable number of both affected and unaffected WS2 individuals exhibited W-index scores consistent with dystopia canthorum. This classification of families might have implications for risk assessment of deafness, since WS2 families had been shown to have greater incidence of deafness. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 REMOVED FROM DATABASE</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 WAARDENBURG SYNDROME TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
|
PAX3, 5-BP DEL, EX5
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<br />
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|
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SNP: rs1559318562,
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|
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ClinVar: RCV000004431
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>'Splotch' is an established mouse model for neural tube defects (NTD). Furthermore, in the human, neural tube defects are occasionally associated with Waardenburg syndrome (Carezani-Gavin et al., 1992; Chatkupt et al., 1993). Hol et al. (1995) screened the PAX3 gene in 39 patients with familial NTD, using single-strand conformation analysis. One patient with lumbosacral meningomyelocele was found to have a 5-bp deletion in exon 5, approximately 55 bp upstream of the conserved homeodomain. The deletion of CAA (gln) and TC caused a frameshift with a stop codon almost immediately after the mutated site; the frameshift led to the insertion of an arg residue before the creation of the stop codon. The patient was found to show mild signs of WS1 (193500). Varying signs of this syndrome were found to cosegregate with the mutation in the family. The results supported the hypothesis that mutations in the gene for PAX3 can also predispose to NTD. It is noteworthy that whereas homozygous Splotch mouse embryos can have NTD, in the heterozygous state mutations of the PAX3 gene do not cause but seem to predispose to NTD in a strain-specific manner. </p>
|
|
</span>
|
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</div>
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 WAARDENBURG SYNDROME, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
WAARDENBURG SYNDROME, TYPE 1, INCLUDED
|
|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
PAX3, SER84PHE
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<br />
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|
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SNP: rs104893651,
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|
|
|
ClinVar: RCV000004432, RCV000004433, RCV003555913
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large kindred with Waardenburg syndrome type 1 (193500), Zlotogora et al. (1995) identified a heterozygous mutation in exon 2 of the PAX3 gene, resulting in a ser84-to-phe (S84F) substitution. However, there was 1 child, born of consanguineous parents, who had a severe phenotype consistent with WS type 3 (148820): this patient was found to be homozygous for the S84F mutation. The child presented with dystopia canthorum, partial albinism, and very severe upper limb defects. Since all Pax3 mutations in mice lead to severe neural tube defects and intrauterine or neonatal death, the survival of the homozygote in this case and the absence of neural tube defects were unexpected. </p>
|
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</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CRANIOFACIAL-DEAFNESS-HAND SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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PAX3, ASN47LYS
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<br />
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|
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SNP: rs104893652,
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|
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ClinVar: RCV000004434, RCV003229799
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Craniofacial-deafness-hand syndrome (122880) was described by Sommer et al. (1983) in a mother and 2 children with absence or hypoplasia of the nasal bones, hypoplastic maxilla, small and sharp nose with thin nares, limited movement of the wrist, short palpebral fissures, ulnar deviation of the fingers, hypertelorism, and profound sensorineural deafness. Asher et al. (1996) demonstrated a PAX3 exon 2 missense mutation, asn47-to-lys (N47K), in the affected members of this family. The affected persons were heterozygous for the mutation. A missense mutation in the same codon, asn47-to-his (606597.0011), gave rise to Waardenburg syndrome type 3. CDHS is clinically distinct from WS3, since affected individuals in the former did not have either muscle or skeletal upper limb hypoplasia; and in families with WS3, a 'pursed' appearance of the mouth and hypoplasia or absence of the nasal bone have not been described. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0011 WAARDENBURG SYNDROME, TYPE 3</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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PAX3, ASN47HIS
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<br />
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SNP: rs104893653,
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ClinVar: RCV000004435
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Waardenburg syndrome type 3 (148820) studied by Goodman et al. (1982) and Sheffer and Zlotogora (1992), Milunsky et al. (1992) and Hoth et al. (1993) identified a heterozygous 352A-C transversion in exon 2 of the PAX3 gene, resulting in an asn47-to-his (N47H) substitution in the paired domain. In addition to telecanthus, blepharophimosis, and hearing loss, affected individuals had hypoplasia of the upper limbs. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0012 WAARDENBURG SYNDROME, TYPE 3</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, 13-BP DEL, NT384
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<br />
|
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SNP: rs1559318494,
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ClinVar: RCV000004436
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>Tekin et al. (2001) described a mother and son with typical clinical findings of WS type 3 (148820) segregating with a heterozygous 13-bp deletion in the paired domain in exon 3 of the PAX3 gene. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0013 WAARDENBURG SYNDROME, TYPE 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, TYR90HIS
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<br />
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SNP: rs104893654,
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ClinVar: RCV000004437
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Wollnik et al. (2003) described a Turkish family in which both of the parents, who were consanguineous, were heterozygous for a 268T-C transition in the PAX3 gene, resulting in a tyr90-to-his (Y90H) substitution. The daughter was homozygous for the mutation and was determined to have type 3 Waardenburg syndrome (148820). Her eyebrows and eyelashes were completely white, the hair was blond, and the irides were blue. The skin was depigmented with spots of normal pigmentation on the upper part of the body. Other findings included relatively large head, small palpebral fissures, increased inner and outer-canthal distances, flexion deformities of wrists, and fingers with ulnar deviation and minimal webs between fingers. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0014 WAARDENBURG SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, ARG56LEU
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<br />
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SNP: rs267606931,
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ClinVar: RCV000004438, RCV001375270, RCV002274876
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with Waardenburg syndrome type 1 (193500), Hoth et al. (1993) identified a heterozygous 380G-T transversion in exon 2 of the PAX3 gene, resulting in an arg56-to-leu (R56L) substitution. One of the affected individuals had a meningomyelocele. The family had been reported by Carezani-Gavin et al. (1992). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0015 WAARDENBURG SYNDROME, TYPE 1</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, HIS80ASP
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<br />
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SNP: rs387906947,
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ClinVar: RCV000023560
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a Chinese boy with Waardenburg syndrome type 1 (193500), Chen et al. (2010) identified a heterozygous 238C-G transversion in exon 2 of the PAX3 gene, resulting in a his80-to-asp (H80D) substitution in the paired domain. The mutant protein retained an intact homeodomain and transactivation domain. Zhang et al. (2012) performed in vitro functional expression studies in human cells, which showed that the H80D mutant protein was expressed and localized to the nucleus, but caused a dramatically reduced activation of MITF (156845) compared to wildtype PAX3. There was no dominant-negative effect of the mutant protein, and the mutant protein could still interact with SOX10 (602229), although it did not enhance the activity of SOX10 as much as wildtype. The findings were consistent with haploinsufficiency as a pathogenic mechanism. The patient had bilateral profound hearing loss, unilateral heterochromia irides, and dystopia canthorum. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0016 WAARDENBURG SYNDROME, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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PAX3, 1-BP DEL, 556C
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<br />
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SNP: rs1559316542,
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ClinVar: RCV000023561
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In a Chinese boy with Waardenburg syndrome type 1 (193500), Chen et al. (2010) identified a heterozygous 1-bp deletion (556delC) in exon 4 of the PAX3 gene, resulting in a frameshift at premature termination at residue 192 (His186fsTer5). The mutant protein would lack the homeodomain and transactivation domain. Zhang et al. (2012) performed in vitro functional expression studies in human cells, which showed that the truncated protein was expressed and localized to both the nucleus and cytoplasm, but failed to activate MITF (156845). There was no dominant-negative effect of the mutant protein, consistent with haploinsufficiency as a pathogenic mechanism. The mutant protein was still able to interact with SOX10 (602229), but did not enhance its activity. The patient had bilateral profound hearing loss, bilateral heterochromia irides, and dystopia canthorum. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Pilz et al. (1993); Wilcox et al. (1992)
|
|
</span>
|
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<div>
|
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<br />
|
|
</div>
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
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Asher, J. H., Jr., Harrison, R. W., Morell, R., Carey, M. L., Friedman, T. B.
|
|
<strong>Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: a murine model of Waardenburg syndrome variation.</strong>
|
|
Genomics 34: 285-298, 1996.
|
|
|
|
|
|
[PubMed: 8786127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0289]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Asher, J. H., Jr., Sommer, A., Morrell, R., Friedman, T. B.
|
|
<strong>Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome.</strong>
|
|
Hum. Mutat. 7: 30-35, 1996.
|
|
|
|
|
|
[PubMed: 8664898]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baldwin, C. T., Hoth, C. F., Amos, J. A., da-Silva, E. O., Milunsky, A.
|
|
<strong>An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.</strong>
|
|
Nature 355: 637-638, 1992.
|
|
|
|
|
|
[PubMed: 1347149]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/355637a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baldwin, C. T., Hoth, C. F., Macina, R. A., Milunsky, A.
|
|
<strong>Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and review of the literature.</strong>
|
|
Am. J. Med. Genet. 58: 115-122, 1995.
|
|
|
|
|
|
[PubMed: 8533800]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320580205]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barber, T. D., Barber, M. C., Cloutier, T. E., Friedman, T. B.
|
|
<strong>PAX3 gene structure, alternative splicing and evolution.</strong>
|
|
Gene 237: 311-319, 1999.
|
|
|
|
|
|
[PubMed: 10521655]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(99)00339-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barr, F. G., Galili, N., Holick, J., Biegel, J. A., Rovera, G., Emanuel, B. S.
|
|
<strong>Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma.</strong>
|
|
Nature Genet. 3: 113-117, 1993.
|
|
|
|
|
|
[PubMed: 8098985]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0293-113]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bondurand, N., Pingault, V., Goerich, D. E., Lemort, N., Sock, E., Le Caignec, C., Wegner, M., Goossens, M.
|
|
<strong>Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome.</strong>
|
|
Hum. Molec. Genet. 9: 1907-1917, 2000.
|
|
|
|
|
|
[PubMed: 10942418]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.13.1907]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bosher, S. K., Hallpike, C. S.
|
|
<strong>Observations on the histogenesis of the inner ear degeneration of the deaf white cat and its possible relationship to the aetiology of certain unexplained varieties of human congenital deafness.</strong>
|
|
J. Laryng. 80: 222-235, 1966.
|
|
|
|
|
|
[PubMed: 5907833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1017/s0022215100065191]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G., Noll, M.
|
|
<strong>Conservation of the paired domain in metazoans and its structure in three isolated human genes.</strong>
|
|
EMBO J. 8: 1183-1190, 1989.
|
|
|
|
|
|
[PubMed: 2501086]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1989.tb03490.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carezani-Gavin, M., Clarren, S. K., Steege, T.
|
|
<strong>Waardenburg syndrome associated with meningomyelocele. (Letter)</strong>
|
|
Am. J. Med. Genet. 42: 135-136, 1992.
|
|
|
|
|
|
[PubMed: 1308353]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320420127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chatkupt, S., Chatkupt, S., Johnson, W. G.
|
|
<strong>Waardenburg syndrome and myelomeningocele in a family.</strong>
|
|
J. Med. Genet. 30: 83-84, 1993.
|
|
|
|
|
|
[PubMed: 8423616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.30.1.83]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H., Jiang, L., Xie, Z., Mei, L., He, C., Hu, Z., Xia, K., Feng, Y.
|
|
<strong>Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome.</strong>
|
|
Biochem. Biophys. Res. Commun. 397: 70-74, 2010.
|
|
|
|
|
|
[PubMed: 20478267]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2010.05.066]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
da-Silva, E. O.
|
|
<strong>Waardenburg I syndrome: a clinical and genetic study of two large Brazilian kindreds, and literature review.</strong>
|
|
Am. J. Med. Genet. 40: 65-74, 1991.
|
|
|
|
|
|
[PubMed: 1887852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320400113]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Morree, A., Klein, J. D. D., Gan, Q., Farup, J., Urtasun, A., Kanugovi, A., Bilen, B., van Velthoven, C. T. J., Quarta, M., Rando, T. A.
|
|
<strong>Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function.</strong>
|
|
Science 366: 734-738, 2019.
|
|
|
|
|
|
[PubMed: 31699935]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aax1694]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Epstein, D. J., Malo, D., Vekemans, M., Gros, P.
|
|
<strong>Molecular characterization of a deletion encompassing the Splotch mutation on mouse chromosome 1.</strong>
|
|
Genomics 10: 89-93, 1991.
|
|
|
|
|
|
[PubMed: 2045114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90488-z]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Epstein, D. J., Vekemans, M., Gros, P.
|
|
<strong>Splotch (Sp-2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3.</strong>
|
|
Cell 67: 767-774, 1991.
|
|
|
|
|
|
[PubMed: 1682057]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(91)90071-6]
|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Epstein, D. J., Vogan, K. J., Trasler, D. G., Gros, P.
|
|
<strong>A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the Splotch (Sp) mouse mutant.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 532-536, 1993.
|
|
|
|
|
|
[PubMed: 8421686]
|
|
|
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|
|
[Full Text: https://doi.org/10.1073/pnas.90.2.532]
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|
|
</p>
|
|
</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Farrer, L. A., Arnos, K. S., Asher, J. H., Jr., Baldwin, C. T., Diehl, S. R., Friedman, T. B., Greenberg, J., Grundfast, K. M., Hoth, C., Lalwani, A. K., Landa, B., Leverton, K., Milunsky, A., Morell, R., Nance, W. E., Newton, V., Ramesar, R., Rao, V. S., Reynolds, J. E., San Agustin, T. B., Wilcox, E. R., Winship, I., Read, A. P.
|
|
<strong>Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes.</strong>
|
|
Am. J. Hum. Genet. 55: 728-737, 1994.
|
|
|
|
|
|
[PubMed: 7942851]
|
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|
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Fleming, A., Copp, A. J.
|
|
<strong>A genetic risk factor for mouse neural tube defects: defining the embryonic basis.</strong>
|
|
Hum. Molec. Genet. 9: 575-581, 2000.
|
|
|
|
|
|
[PubMed: 10699180]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/9.4.575]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Fortin, A. S., Underhill, D. A., Gros, P.
|
|
<strong>Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain.</strong>
|
|
Hum. Molec. Genet. 6: 1781-1790, 1997.
|
|
|
|
|
|
[PubMed: 9302254]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/6.11.1781]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Fredericks, W. J., Galili, N., Mukhopadhyay, S., Rovera, G., Bennicelli, J., Barr, F. G., Rauscher, F. J., III.
|
|
<strong>The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3.</strong>
|
|
Molec. Cell. Biol. 15: 1522-1535, 1995.
|
|
|
|
|
|
[PubMed: 7862145]
|
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|
|
[Full Text: https://doi.org/10.1128/MCB.15.3.1522]
|
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Galili, N., Davis, R. J., Fredericks, W. J., Mukhopadhyay, S., Rauscher, F. J., III, Emanuel, B. S., Rovera, G., Barr, F. G.
|
|
<strong>Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma.</strong>
|
|
Nature Genet. 5: 230-235, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.
|
|
|
|
|
|
[PubMed: 8275086]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1193-230]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ganguly, A., Rock, M. J., Prockop, D. J.
|
|
<strong>Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 10325-10329, 1993. Note: Erratum: Proc. Nat. Acad. Sci. 91: 5217 only, 1994.
|
|
|
|
|
|
[PubMed: 8234293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.90.21.10325]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goodman, R. M., Lewithal, I., Solomon, A., Klein, D.
|
|
<strong>Upper limb involvement in the Klein-Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 11: 425-433, 1982.
|
|
|
|
|
|
[PubMed: 7091186]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320110407]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goulding, M. D., Chalepakis, G., Deutsch, U., Erselius, J. R., Gruss, P.
|
|
<strong>Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.</strong>
|
|
EMBO J. 10: 1135-1147, 1991.
|
|
|
|
|
|
[PubMed: 2022185]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1991.tb08054.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hol, F. A., Hamel, B. C. J., Geurds, M. P. A., Mullaart, R. A., Barr, F. G., Macina, R. A., Mariman, E. C. M.
|
|
<strong>A frameshift mutation in the gene for PAX3 in a girl with spina bifida and mild signs of Waardenburg syndrome.</strong>
|
|
J. Med. Genet. 32: 52-56, 1995.
|
|
|
|
|
|
[PubMed: 7897628]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.1.52]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoth, C. F., Milunsky, A., Lipsky, N., Sheffer, R., Clarren, S. K., Baldwin, C. T.
|
|
<strong>Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).</strong>
|
|
Am. J. Hum. Genet. 52: 455-462, 1993.
|
|
|
|
|
|
[PubMed: 8447316]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ishikiriyama, S., Tonoki, H., Shibuya, Y., Chin, S., Harada, N., Abe, K., Niikawa, N.
|
|
<strong>Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3).</strong>
|
|
Am. J. Med. Genet. 33: 505-507, 1989.
|
|
|
|
|
|
[PubMed: 2596512]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320330419]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ishikiriyama, S.
|
|
<strong>Gene for Waardenburg syndrome type I is located at 2q35, not at 2q37.3. (Letter)</strong>
|
|
Am. J. Med. Genet. 46: 608, 1993.
|
|
|
|
|
|
[PubMed: 8322830]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320460534]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jacobs-Cohen, R. J., Payette, R. F., Gershon, M. D., Rothman, T. P.
|
|
<strong>Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive environment.</strong>
|
|
J. Comp. Neurol. 255: 425-438, 1987.
|
|
|
|
|
|
[PubMed: 3819023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/cne.902550309]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Khan, J., Bittner, M. L., Saal, L. H., Teichmann, U., Azorsa, D. O., Gooden, G. C., Pavan, W. J., Trent, J. M., Meltzer, P. S.
|
|
<strong>cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 13264-13269, 1999.
|
|
|
|
|
|
[PubMed: 10557309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.23.13264]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lagutina, I., Conway, S. J., Sublett, J., Grosveld, G. C.
|
|
<strong>Pax3-FKHR knock-in mice show developmental aberrations but do not develop tumors.</strong>
|
|
Molec. Cell. Biol. 22: 7204-7216, 2002.
|
|
|
|
|
|
[PubMed: 12242297]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.22.20.7204-7216.2002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lang, D., Epstein, J. A.
|
|
<strong>Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer.</strong>
|
|
Hum. Molec. Genet. 12: 937-945, 2003.
|
|
|
|
|
|
[PubMed: 12668617]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg107]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lang, D., Lu, M. M., Huang, L., Engelka, K. A., Zhang, M., Chu, E. Y., Lipner, S., Skoultchi, A., Millar, S. E., Epstein, J. A.
|
|
<strong>Pax3 functions at a nodal point in melanocyte stem cell differentiation.</strong>
|
|
Nature 433: 884-887, 2005.
|
|
|
|
|
|
[PubMed: 15729346]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature03292]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Macina, R. A., Barr, F. G., Galili, N., Riethman, H. C.
|
|
<strong>Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma.</strong>
|
|
Genomics 26: 1-8, 1995.
|
|
|
|
|
|
[PubMed: 7782066]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80076-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milunsky, A., Lipsky, N., Sheffer, R., Zlotogora, J., Baldwin, C.
|
|
<strong>A mutation in the Waardenburg syndrome (WS-I) gene in a family with 'WS-III'. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A222, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milunsky, A.
|
|
<strong>Personal Communication.</strong>
|
|
Boston, Mass. 3/4/1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moase, C. E., Trasler, D. G.
|
|
<strong>Splotch locus mouse mutants: models for neural tube defects and Waardenburg syndrome type I in humans.</strong>
|
|
J. Med. Genet. 29: 145-151, 1992.
|
|
|
|
|
|
[PubMed: 1552554]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.29.3.145]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morell, R., Friedman, T. B., Moeljopawiro, S., Hartono, (NI), Soewito, (NI), Asher, J. H., Jr.
|
|
<strong>A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.</strong>
|
|
Hum. Molec. Genet. 1: 243-247, 1992.
|
|
|
|
|
|
[PubMed: 1303193]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/1.4.243]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Motohashi, H., Hozawa, K., Oshima, T., Takeuchi, T., Takasaka, T.
|
|
<strong>Dysgenesis of melanocytes and cochlear dysfunction in mutant microphthalmia (mi) mice.</strong>
|
|
Hear. Res. 80: 10-20, 1994.
|
|
|
|
|
|
[PubMed: 7852195]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0378-5955(94)90003-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., Markham, A. F.
|
|
<strong>Analysis of any point mutation in DNA: the amplification refractory mutation system (ARMS).</strong>
|
|
Nucleic Acids Res. 17: 2503-2516, 1989.
|
|
|
|
|
|
[PubMed: 2785681]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/17.7.2503]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pilz, A. J., Povey, S., Gruss, P., Abbott, C. M.
|
|
<strong>Mapping of the human homologs of the murine paired-box-containing genes.</strong>
|
|
Mammalian Genome 4: 78-82, 1993.
|
|
|
|
|
|
[PubMed: 8431641]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00290430]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pritchard, C., Grosveld, G., Hollenbach, A. D.
|
|
<strong>Alternative splicing of Pax3 produces a transcriptionally inactive protein.</strong>
|
|
Gene 305: 61-69, 2003.
|
|
|
|
|
|
[PubMed: 12594042]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(02)01186-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Relaix, F., Polimeni, M., Rocancourt, D., Ponzetto, C., Schafer, B. W., Buckingham, M.
|
|
<strong>The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo.</strong>
|
|
Genes Dev. 17: 2950-2965, 2003.
|
|
|
|
|
|
[PubMed: 14665670]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.281203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Relaix, F., Rocancourt, D., Mansouri, A., Buckingham, M.
|
|
<strong>A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. (Letter)</strong>
|
|
Nature 435: 948-953, 2005.
|
|
|
|
|
|
[PubMed: 15843801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature03594]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reynolds, J. E., Meyer, J. M., Landa, B., Stevens, C. A., Arnos, K. S., Israel, J., Marazita, M. L., Bodurtha, J., Nance, W. E., Diehl, S. R.
|
|
<strong>Analysis of variability of clinical manifestations in Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 57: 540-547, 1995.
|
|
|
|
|
|
[PubMed: 7573125]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320570405]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ridgeway, A. G., Skerjanc, I. S.
|
|
<strong>Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2.</strong>
|
|
J. Biol. Chem. 276: 19033-19039, 2001.
|
|
|
|
|
|
[PubMed: 11262400]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M011491200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roeb, W., Boyer, A., Cavenee, W. K., Arden, K. C.
|
|
<strong>PAX3-FOXO1 controls expression of the p57Kip2 cell-cycle regulator through degradation of EGR1.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 18085-18090, 2007.
|
|
|
|
|
|
[PubMed: 17986608]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0708910104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scheidler, S., Fredericks, W. J., Rauscher, F. J., III, Barr, F. G., Vogt, P. K.
|
|
<strong>The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 9805-9809, 1996.
|
|
|
|
|
|
[PubMed: 8790412]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.18.9805]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sheffer, R., Zlotogora, J.
|
|
<strong>Autosomal dominant inheritance of Klein-Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 42: 320-322, 1992.
|
|
|
|
|
|
[PubMed: 1536170]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320420312]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sommer, A., Young-Wee, T., Frye, T.
|
|
<strong>Previously undescribed syndrome of craniofacial, hand anomalies, and sensorineural deafness.</strong>
|
|
Am. J. Med. Genet. 15: 71-77, 1983.
|
|
|
|
|
|
[PubMed: 6859126]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320150109]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Steel, K. P., Smith, R. J. H.
|
|
<strong>Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1.</strong>
|
|
Nature Genet. 2: 75-79, 1992.
|
|
|
|
|
|
[PubMed: 1303254]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0992-75]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sublett, J. E., Jeon, I-S., Shapiro, D. N.
|
|
<strong>The alveolar rhabdomyosarcoma PAX3/FKHR fusion protein is a transcriptional activator.</strong>
|
|
Oncogene 11: 545-552, 1995.
|
|
|
|
|
|
[PubMed: 7630639]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tachibana, M., Takeda, K., Nobukuni, Y., Urabe, K., Long, J. E., Meyers, K. A., Aaronson, S. A., Miki, T.
|
|
<strong>Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocytes characteristics.</strong>
|
|
Nature Genet. 14: 50-54, 1996.
|
|
|
|
|
|
[PubMed: 8782819]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0996-50]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tassabehji, M., Newton, V. E., Liu, X.-Z., Brady, A., Donnai, D., Krajewska-Walasek, M., Murday, V., Norman, A., Obersztyn, E., Reardon, W., Rice, J. C., Trembath, R., Wieacker, P., Whiteford, M., Winter, R., Read, A. P.
|
|
<strong>The mutational spectrum in Waardenburg syndrome.</strong>
|
|
Hum. Molec. Genet. 4: 2131-2137, 1995.
|
|
|
|
|
|
[PubMed: 8589691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.11.2131]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tassabehji, M., Read, A. P., Newton, V. E., Harris, R., Balling, R., Gruss, P., Strachan, T.
|
|
<strong>Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.</strong>
|
|
Nature 355: 635-636, 1992.
|
|
|
|
|
|
[PubMed: 1347148]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/355635a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tassabehji, M., Read, A. P., Newton, V. E., Patton, M., Gruss, P., Harris, R., Strachan, T.
|
|
<strong>Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.</strong>
|
|
Nature Genet. 3: 26-30, 1993.
|
|
|
|
|
|
[PubMed: 8490648]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0193-26]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tekin, M., Bodurtha, J. N., Nance, W. E., Pandya, A.
|
|
<strong>Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome?</strong>
|
|
Clin. Genet. 60: 301-304, 2001.
|
|
|
|
|
|
[PubMed: 11683776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2001.600408.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsukamoto, K., Nakamura, Y., Niikawa, N.
|
|
<strong>Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues.</strong>
|
|
Hum. Genet. 93: 270-274, 1994.
|
|
|
|
|
|
[PubMed: 7545913]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00212021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Tsukamoto, K., Tohma, T., Ohta, T., Yamakawa, K., Fukushima, Y., Nakamura, Y., Niikawa, N.
|
|
<strong>Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I.</strong>
|
|
Hum. Molec. Genet. 1: 315-317, 1992.
|
|
|
|
|
|
[PubMed: 1303207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/1.5.315]
|
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|
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</p>
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Watanabe, A., Takeda, K., Ploplis, B., Tachibana, M.
|
|
<strong>Epistatic relationship between Waardenburg syndrome genes MITF and PAX3.</strong>
|
|
Nature Genet. 18: 283-286, 1998.
|
|
|
|
|
|
[PubMed: 9500554]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0398-283]
|
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|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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Wilcox, E. R., Rivolta, M. N., Ploplis, B., Potterf, S. B., Fex, J.
|
|
<strong>The PAX3 gene is mapped to human chromosome 2 together with a highly informative CA dinucleotide repeat.</strong>
|
|
Hum. Molec. Genet. 1: 215, 1992.
|
|
|
|
|
|
[PubMed: 1303187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/1.3.215-a]
|
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</p>
|
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</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
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Wildhardt, G., Winterpacht, A., Hibert, K., Menger, H., Zabel, B.
|
|
<strong>Two different PAX3 gene mutations causing Waardenburg syndrome type I.</strong>
|
|
Molec. Cell. Probes 10: 229-231, 1996.
|
|
|
|
|
|
[PubMed: 8799378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/mcpr.1996.0032]
|
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|
|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
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Wollnik, B., Tukel, T., Uyguner, O., Ghanbari, A., Kayserili, H., Emiroglu, M., Yuksel-Apak, M.
|
|
<strong>Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome.</strong>
|
|
Am. J. Med. Genet. 122A: 42-45, 2003.
|
|
|
|
|
|
[PubMed: 12949970]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20260]
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</p>
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</li>
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<li>
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Zhang, H., Chen, H., Luo, H., An, J., Sun, L., Mei, L., He, C., Jiang, L., Jiang, W., Xia, K., Li, J.-D., Feng, Y.
|
|
<strong>Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.</strong>
|
|
Hum. Genet. 131: 491-503, 2012.
|
|
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|
|
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[PubMed: 21965087]
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[Full Text: https://doi.org/10.1007/s00439-011-1098-2]
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Zlotogora, J., Lerer, I., Bar-David, S., Ergaz, Z., Abeliovich, D.
|
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<strong>Homozygosity for Waardenburg syndrome.</strong>
|
|
Am. J. Hum. Genet. 56: 1173-1178, 1995.
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[PubMed: 7726174]
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