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Entry
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- *142959 - HOMEOBOX A13; HOXA13
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- OMIM
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<p>
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<span class="h4">*142959</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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 role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</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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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/142959">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<h4 class="panel-title">
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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 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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<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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</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=ENSG00000106031;t=ENST00000649031" 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=3209" 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=142959" 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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<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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<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=ENSG00000106031;t=ENST00000649031" 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_000522" 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_000522" 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=142959" 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=00847&isoform_id=00847_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/HOXA13" 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/1832353,24497554,50370280,51094974,116242513,119614296,350543074" 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/P31271" 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 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=3209" 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=ENSG00000106031;t=ENST00000649031" 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=HOXA13" 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=HOXA13" 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+3209" 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/HOXA13" 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:3209" 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/3209" 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=chr7&hgg_gene=ENST00000649031.1&hgg_start=27194364&hgg_end=27200091&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 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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</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://medlineplus.gov/genetics/gene/hoxa13" 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=142959[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=142959[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/HOXA13/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/ENSG00000106031" 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=HOXA13" 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=HOXA13" 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=HOXA13" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HOXA13&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/PA29379" 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:5102" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96173" 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/HOXA13#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:96173" 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/3209/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3209" 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-980526-365" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=HOXA13&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> 702425002, 722452004<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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142959
|
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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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HOMEOBOX A13; HOXA13
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
HOMEOBOX 1J; HOX1J
|
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</span>
|
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HOXA13" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HOXA13</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/7/145?start=-3&limit=10&highlight=145">7p15.2</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:27194364-27200091&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'})">7:27,194,364-27,200,091</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=176305,140000" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
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</th>
|
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/145?start=-3&limit=10&highlight=145">
|
|
7p15.2
|
|
</a>
|
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</span>
|
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</td>
|
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|
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|
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<td>
|
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<span class="mim-font">
|
|
?Guttmacher syndrome
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|
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<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
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</span>
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/176305"> 176305 </a>
|
|
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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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>
|
|
<span class="mim-font">
|
|
Hand-foot-genital syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/140000"> 140000 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
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</tbody>
|
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</table>
|
|
</div>
|
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/142959" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/142959" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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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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<br />
|
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</div>
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<div>
|
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<a id="text" class="mim-anchor"></a>
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<p>For background information on homeobox genes, see HOXA7 (<a href="/entry/142950">142950</a>).</p>
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<p><a href="#11" class="mim-tip-reference" title="Mortlock, D. P., Innis, J. W. <strong>Mutation of HOXA13 in hand-foot-genital syndrome.</strong> Nature Genet. 15: 179-181, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9020844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9020844</a>] [<a href="https://doi.org/10.1038/ng0297-179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9020844">Mortlock and Innis (1997)</a> determined the complete coding sequence for HOXA13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9020844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#14" class="mim-tip-reference" title="Rinn, J. L., Wang, J. K., Allen, N., Brugmann, S. A., Mikels, A. J., Liu, H., Ridky, T. W., Stadler, H. S., Nusse, R., Helms, J. A., Chang, H. Y. <strong>A dermal HOX transcriptional program regulates site-specific epidermal fate.</strong> Genes Dev. 22: 303-307, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18245445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18245445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18245445[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.1610508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18245445">Rinn et al. (2008)</a> stated that fibroblasts obtained from anatomically distinct sites of human skin express genes in a site-specific manner. By microarray analysis of cultured fibroblasts derived from foot or thigh, followed by comparing gene expression profiles of primary fibroblasts from 43 anatomic sites, <a href="#14" class="mim-tip-reference" title="Rinn, J. L., Wang, J. K., Allen, N., Brugmann, S. A., Mikels, A. J., Liu, H., Ridky, T. W., Stadler, H. S., Nusse, R., Helms, J. A., Chang, H. Y. <strong>A dermal HOX transcriptional program regulates site-specific epidermal fate.</strong> Genes Dev. 22: 303-307, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18245445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18245445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18245445[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.1610508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18245445">Rinn et al. (2008)</a> found that HOXA13 expression was associated with distal sites and was required for activation of distal-specific gene expression, including expression of WNT5A (<a href="/entry/164975">164975</a>). Depletion of HOXA13 in human plantar fibroblasts reduced expression of distal-specific keratin-9 (KRT9; <a href="/entry/607606">607606</a>), and KRT9 expression was rescued by addition of recombinant purified WNT5A. In situ hybridization showed that Hoxa13 and Wnt5a were spatially and temporally coexpressed in distal limb bud during mouse development. <a href="#14" class="mim-tip-reference" title="Rinn, J. L., Wang, J. K., Allen, N., Brugmann, S. A., Mikels, A. J., Liu, H., Ridky, T. W., Stadler, H. S., Nusse, R., Helms, J. A., Chang, H. Y. <strong>A dermal HOX transcriptional program regulates site-specific epidermal fate.</strong> Genes Dev. 22: 303-307, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18245445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18245445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18245445[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.1610508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18245445">Rinn et al. (2008)</a> concluded that HOXA13 control of WNT5A expression in distal fibroblasts can regulate site-specific epidermal differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18245445" 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="Sheth, R., Marcon, L., Bastida, M. F., Junco, M., Quintana, L., Dahn, R., Kmita M., Sharpe, J., Ros, M. A. <strong>Hox genes regulate digit patterning by controlling the wavelength of a Turing-type mechanism.</strong> Science 338: 1476-1480, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23239739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23239739</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23239739[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.1226804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23239739">Sheth et al. (2012)</a> used mouse genetics to analyze how digit patterning (an iterative digit/nondigit pattern) is generated and showed that the progressive reduction in Hoxa13 and Hoxd11 (<a href="/entry/142986">142986</a>)-Hoxd13 (<a href="/entry/142989">142989</a>) genes (hereafter referred to as distal Hox genes) from the Gli3 (<a href="/entry/165240">165240</a>)-null background results in progressively more severe polydactyly, displaying thinner and densely packed digits. Combined with computer modeling, their results argued for a Turing-type mechanism underlying digit patterning, in which the dose of distal Hox genes modulates the digit period or wavelength. The phenotypic similarity of fish-fin endoskeleton patterns suggested that the pentadactyl state has been achieved through modification of an ancestral Turing-type mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23239739" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Kherdjemil, Y., Lalonde, R. L., Sheth, R., Dumouchel, A., de Martino, G., Pineault, K. M., Wellik, D. M., Stadler, H. S., Akimenko, M. A., Kmita, M. <strong>Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state.</strong> Nature 539: 89-92, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27706137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27706137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27706137[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/10.1038/nature19813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27706137">Kherdjemil et al. (2016)</a> showed that the mutually exclusive expression of the mouse genes Hoxa11 (<a href="/entry/142958">142958</a>) and Hoxa13, which had been proposed to be involved in the origin of the tetrapod limb, is required for the pentadactyl state. <a href="#10" class="mim-tip-reference" title="Kherdjemil, Y., Lalonde, R. L., Sheth, R., Dumouchel, A., de Martino, G., Pineault, K. M., Wellik, D. M., Stadler, H. S., Akimenko, M. A., Kmita, M. <strong>Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state.</strong> Nature 539: 89-92, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27706137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27706137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27706137[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/10.1038/nature19813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27706137">Kherdjemil et al. (2016)</a> further demonstrated that the exclusion of Hoxa11 from the Hoxa13 domain relies on an enhancer that drives antisense transcription at the Hoxa11 locus after activation by Hoxa13 and Hoxd13. Finally, the authors showed that the enhancer that drives antisense transcription of the mouse Hoxa11 gene is absent in zebrafish, which, together with the largely overlapping expression of hoxa11 and hoxa13 genes reported in fish, suggested that this enhancer emerged in the course of the fin-to-limb transition. On the basis of the polydactyly that was observed after expression of Hoxa11 in distal limbs, <a href="#10" class="mim-tip-reference" title="Kherdjemil, Y., Lalonde, R. L., Sheth, R., Dumouchel, A., de Martino, G., Pineault, K. M., Wellik, D. M., Stadler, H. S., Akimenko, M. A., Kmita, M. <strong>Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state.</strong> Nature 539: 89-92, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27706137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27706137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27706137[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/10.1038/nature19813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27706137">Kherdjemil et al. (2016)</a> proposed that the evolution of Hoxa11 regulation contributed to the transition from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant tetrapods. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27706137" 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>HOXA13 belongs to the cluster of homeobox genes on chromosome 7. As reviewed by <a href="#1" class="mim-tip-reference" title="Acampora, D., D'Esposito, M., Faiella, A., Pannese, M., Migliaccio, E., Morelli, F., Stornaiuolo, A., Nigro, V., Simeone, A., Boncinelli, E. <strong>The human HOX gene family.</strong> Nucleic Acids Res. 17: 10385-10402, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2574852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2574852</a>] [<a href="https://doi.org/10.1093/nar/17.24.10385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2574852">Acampora et al. (1989)</a>, the homeobox region 1 includes at least 8 homeobox genes in 90 kb of DNA located on chromosome 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2574852" 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="#13" class="mim-tip-reference" title="Mortlock, D. P. <strong>Personal Communication.</strong> Ann Arbor, Mich. 10/31/1996."None>Mortlock (1996)</a> found a mutation in the HOXA13 gene resulting in hand-foot-uterus (HFU) syndrome, also known as hand-foot-genital (HFG) syndrome (<a href="/entry/140000">140000</a>). Their observations were made in the family reported by <a href="#18" class="mim-tip-reference" title="Stern, A. M., Gall, J. C., Jr., Perry, B. L., Stimson, C. W., Weitkamp, L. R., Poznanski, A. K. <strong>The hand-foot-uterus syndrome: a new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract.</strong> J. Pediat. 77: 109-116, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450271</a>] [<a href="https://doi.org/10.1016/s0022-3476(70)80052-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5450271">Stern et al. (1970)</a>. This was the second mutation discovered in a HOX gene as the cause of a malformation; the first to be discovered was the mutation in HOXD13 (<a href="/entry/142989">142989</a>) as the cause of synpolydactyly (<a href="/entry/186000">186000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5450271" 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="#11" class="mim-tip-reference" title="Mortlock, D. P., Innis, J. W. <strong>Mutation of HOXA13 in hand-foot-genital syndrome.</strong> Nature Genet. 15: 179-181, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9020844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9020844</a>] [<a href="https://doi.org/10.1038/ng0297-179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9020844">Mortlock and Innis (1997)</a> found that affected members of an HFG syndrome family reported by <a href="#18" class="mim-tip-reference" title="Stern, A. M., Gall, J. C., Jr., Perry, B. L., Stimson, C. W., Weitkamp, L. R., Poznanski, A. K. <strong>The hand-foot-uterus syndrome: a new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract.</strong> J. Pediat. 77: 109-116, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450271</a>] [<a href="https://doi.org/10.1016/s0022-3476(70)80052-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5450271">Stern et al. (1970)</a> had a mutation in the HOXA13 gene that converted a highly conserved tryptophan residue in the homeodomain to a stop codon with resulting truncation of 20 amino acids from the protein (<a href="#0001">142959.0001</a>). It was thought that the mutation probably eliminated or greatly reduced the ability of the protein to bind to DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5450271+9020844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J. <strong>Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.</strong> Am. J. Hum. Genet. 67: 197-202, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839976</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10839976[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10839976">Goodman et al. (2000)</a> examined the HOXA13 gene in 2 new and 4 previously reported families with features of HFG syndrome. In 3 families, nonsense mutations truncating the encoded protein N-terminal to or within the homeodomain produced typical limb and genitourinary abnormalities; in the fourth family, an expansion of an N-terminal polyalanine tract produced a similar phenotype; in the fifth family, a missense mutation, which altered an invariant domain, produced an exceptionally severe limb phenotype; and in the sixth family, in which limb abnormalities were atypical, no HOXA13 mutation was detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10839976" 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 polyalanine expansion reported by <a href="#6" class="mim-tip-reference" title="Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J. <strong>Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.</strong> Am. J. Hum. Genet. 67: 197-202, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839976</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10839976[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10839976">Goodman et al. (2000)</a> occurred in exon 1 following nucleotide 388 and resulting in the in-frame insertion of 24-bp and an additional 8 alanine residues (<a href="#0003">142959.0003</a>). <a href="#19" class="mim-tip-reference" title="Utsch, B., Becker, K., Brock, D., Lentze, M. J., Bidlingmaier, F., Ludwig, M. <strong>A novel stable polyalanine (poly(A)) expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length?</strong> Hum. Genet. 110: 488-494, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073020</a>] [<a href="https://doi.org/10.1007/s00439-002-0712-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073020">Utsch et al. (2002)</a> reported a similar in-frame expansion of 6 alanines also in exon 1, following nucleotide 376, of the HOXA13 gene (<a href="#0006">142959.0006</a>). They pointed out that expansion by 7 up to 14 alanine residues occurs in the HOXD13 gene, resulting in synpolydactyly. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10839976+12073020" 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>Guttmacher syndrome (<a href="/entry/176305">176305</a>) has a number of features in common with hand-foot-genital syndrome, including hypoplastic thumbs and halluces, fifth-finger clinobrachydactyly, and hypospadias. However, 2 of its features, postaxial polydactyly of the hands and short or uniphalangeal second toes with absent nails, had never been observed in patients with hand-foot-genital syndrome. Because of the similarities, <a href="#8" class="mim-tip-reference" title="Innis, J. W., Goodman, F. R., Bacchelli, C., Williams, T. M., Mortlock, D. P., Sateesh, P., Scambler, P. J., McKinnon, W., Guttmacher, A. E. <strong>A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome. (Abstract)</strong> Hum. Mutat. 19: 573-574, 2002."None>Innis et al. (2002)</a> reinvestigated the family originally described by <a href="#7" class="mim-tip-reference" title="Guttmacher, A. E. <strong>Autosomal dominant preaxial deficiency, postaxial polydactyly, and hypospadias.</strong> Am. J. Med. Genet. 46: 219-222, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8484413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8484413</a>] [<a href="https://doi.org/10.1002/ajmg.1320460223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8484413">Guttmacher (1993)</a>. They found that affected individuals were heterozygous for a novel missense mutation in the HOXA13 homeobox (Q50L; <a href="#0005">142959.0005</a>), which arose on an allele already carrying a novel 2-bp deletion (involving GC at positions -78 and -79) in the gene's highly conserved promoter region. This promoter deletion produces no detectable abnormalities on its own, but may have contributed to the phenotype in the affected individuals. The missense mutation, which altered a key residue in the recognition helix of the homeodomain, is likely to perturb HOXA13's DNA-binding properties, resulting in both a loss and a specific gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8484413" 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="#12" class="mim-tip-reference" title="Mortlock, D. P., Post, L. C., Innis, J. W. <strong>The molecular basis of hypodactyly (Hd): a deletion in Hoxa13 leads to arrest of digital arch formation.</strong> Nature Genet. 13: 284-289, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673126</a>] [<a href="https://doi.org/10.1038/ng0796-284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673126">Mortlock et al. (1996)</a> found a 50-bp deletion in the first exon of the Hoxa13 gene in mice with the semidominant mutation 'Hypodactyly' (Hd). The mutation was known to map to a genetic interval overlapping the Hoxa cluster on mouse chromosome 6. They stated that the deletion probably arose from unequal recombination between triplet repeats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673126" 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="#9" class="mim-tip-reference" title="Innis, J. W., Mortlock, D., Chen, Z., Ludwig, M., Williams, M. E., Williams, T. M., Doyle, C. D., Shao, Z., Glynn, M., Mikulic, D., Lehmann, K., Mundlos, S., Utsch, B. <strong>Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model.</strong> Hum. Molec. Genet. 13: 2841-2851, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15385446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15385446</a>] [<a href="https://doi.org/10.1093/hmg/ddh306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15385446">Innis et al. (2004)</a> performed homologous recombination in murine embryonic stem cells to expand the size of the third largest polyalanine tract by 10 residues. Mutant mice were indistinguishable from Hoxa13-null mice. Mutant limb buds had normal steady-state Hoxa13 RNA expression, normal mRNA splicing, and reduced levels of steady-state protein. In vitro translation efficiency of the mutant protein was normal. <a href="#9" class="mim-tip-reference" title="Innis, J. W., Mortlock, D., Chen, Z., Ludwig, M., Williams, M. E., Williams, T. M., Doyle, C. D., Shao, Z., Glynn, M., Mikulic, D., Lehmann, K., Mundlos, S., Utsch, B. <strong>Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model.</strong> Hum. Molec. Genet. 13: 2841-2851, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15385446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15385446</a>] [<a href="https://doi.org/10.1093/hmg/ddh306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15385446">Innis et al. (2004)</a> concluded that loss of function was secondary to reduced levels of the expanded protein in vivo, likely due to degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15385446" 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>Late limb buds of all tetrapods contain 3 proximodistal segments, each expressing specific homeobox genes. The stylopod (upper limb) expresses Meis1/2 (see <a href="/entry/601739">601739</a>), the zeugopod (lower limb) expresses Hoxa11 (<a href="/entry/142958">142958</a>), and the autopod (hand/foot) Hoxa13, although none of these markers is sufficient to specify limb-segment identity (summary by <a href="#15" class="mim-tip-reference" title="Rosello-Diez, A., Ros, M. A., Torres, M. <strong>Diffusible signals, not autonomous mechanisms, determine the main proximodistal limb subdivision.</strong> Science 332: 1086-1088, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21617076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21617076</a>] [<a href="https://doi.org/10.1126/science.1199489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21617076">Rosello-Diez et al., 2011</a>). <a href="#2" class="mim-tip-reference" title="Cooper, K. L., Hu, J. K.-H., ten Berge, D., Fernandez-Teran, M., Ros, M. A., Tabin, C. J. <strong>Initiation of proximal-distal patterning in the vertebrate limb by signals and growth.</strong> Science 332: 1083-1086, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21617075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21617075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21617075[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.1199499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21617075">Cooper et al. (2011)</a> showed that Wnt3a (<a href="/entry/606359">606359</a>), Fgf8 (<a href="/entry/600483">600483</a>), and retinoic acid act together to maintain markers of early limb mesenchyme in culture. <a href="#15" class="mim-tip-reference" title="Rosello-Diez, A., Ros, M. A., Torres, M. <strong>Diffusible signals, not autonomous mechanisms, determine the main proximodistal limb subdivision.</strong> Science 332: 1086-1088, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21617076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21617076</a>] [<a href="https://doi.org/10.1126/science.1199489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21617076">Rosello-Diez et al. (2011)</a> showed that the first limb bud proximodistal regionalization results from the balance between proximal and distal signals. The results of both groups suggested that retinoic acid is the trunk proximalizing signal and that the trigger for initiating the process of specification of the zeugopod and autopod is the cessation (due to displacement) of retinoic acid exposure, and argued against a mechanism linking proximodistal specification to a cell cycle-based internal clock. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21617075+21617076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Roux, M., Bouchard, M., Kmita, M. <strong>Multifaceted Hoxa13 function in urogenital development underlies the hand-foot-genital syndrome.</strong> Hum. Molec. Genet. 28: 1671-1681, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30649340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30649340</a>] [<a href="https://doi.org/10.1093/hmg/ddz013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30649340">Roux et al. (2019)</a> found that mice with conditional knockout of Hoxa13 displayed megaureter phenotype due to abnormal ureter insertion caused by defective common nephric duct elimination. The severity of the hydroureter phenotype was likely associated with delayed ureter maturation in Hoxa13 mutant mice. In addition, Hoxa13 mutant mice displayed defective Mullerian duct fusion similar to that found in female patients with HFG syndrome. In situ hybridization analysis revealed that Hoxa13 acted upstream of Ret (<a href="/entry/164761">164761</a>) and Gata3 (<a href="/entry/131320">131320</a>) and impacted Ret expression through Gata3. Furthermore, Gata3 played a mediator role on Hoxa13 function in the urogenital sinus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30649340" 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="#11" class="mim-tip-reference" title="Mortlock, D. P., Innis, J. W. <strong>Mutation of HOXA13 in hand-foot-genital syndrome.</strong> Nature Genet. 15: 179-181, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9020844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9020844</a>] [<a href="https://doi.org/10.1038/ng0297-179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9020844">Mortlock and Innis (1997)</a> found that patients with the hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>) in the family reported by <a href="#18" class="mim-tip-reference" title="Stern, A. M., Gall, J. C., Jr., Perry, B. L., Stimson, C. W., Weitkamp, L. R., Poznanski, A. K. <strong>The hand-foot-uterus syndrome: a new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract.</strong> J. Pediat. 77: 109-116, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450271</a>] [<a href="https://doi.org/10.1016/s0022-3476(70)80052-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5450271">Stern et al. (1970)</a> had an A-to-G transition in a highly conserved tryptophan codon in the HOXA13 homeodomain, which, in addition to causing a trp369-to-ter substitution (TGG to TGA), also destroyed a NlaIV restriction site. The nonsense mutation was predicted to produce a truncated protein missing 20 C-terminal amino acids based on homology to other homeodomains whose 3-dimensional structures had been determined. This portion of the normal homeodomain folds into the last of the 3 alpha-helices. This helix is critical for DNA binding. The authors noted that the tryptophan that was mutated in this family is the only amino acid which is invariant in all known homeodomain proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5450271+9020844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016019" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016019" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016019</a>
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<p><a href="#6" class="mim-tip-reference" title="Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J. <strong>Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.</strong> Am. J. Hum. Genet. 67: 197-202, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839976</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10839976[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10839976">Goodman et al. (2000)</a> identified a nonsense truncating mutation in a male patient who had hand and foot abnormalities typical of hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>), as well as a short penis tethered inferiorly to the scrotal sac. The predicted truncated protein in this individual lacked the entire homeodomain of the HOXA13 protein. The proband was heterozygous for an A-to-C substitution in exon 1 at base 407 (number of bases starting at the first residue of the initiated codon). The mutation converted a serine residue to a stop codon and was predicted to result in a truncated protein containing only the first 135 amino acids of the wildtype protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10839976" 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 HAND-FOOT-GENITAL SYNDROME</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016020" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016020" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016020</a>
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<p>In the family (family 4) with hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>) in multiple generations reported by <a href="#5" class="mim-tip-reference" title="Elias, S., Simpson, J. L., Feingold, M., Sarto, G. E. <strong>The hand-foot-uterus syndrome: a rare autosomal dominant disorder.</strong> Fertil. Steril. 29: 239-240, 1978."None>Elias et al. (1978)</a>, <a href="#21" class="mim-tip-reference" title="Verp, M. S. <strong>Urinary tract abnormalities in hand-foot-genital syndrome.</strong> Am. J. Med. Genet. 32: 555 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2774004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2774004</a>] [<a href="https://doi.org/10.1002/ajmg.1320320429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2774004">Verp (1989)</a>, and <a href="#4" class="mim-tip-reference" title="Donnenfeld, A. E., Schrager, D. S., Corson, S. L. <strong>Update on a family with hand-foot-genital syndrome: hypospadias and urinary tract abnormalities in two boys from the fourth generation.</strong> Am. J. Med. Genet. 44: 482-484, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1442892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1442892</a>] [<a href="https://doi.org/10.1002/ajmg.1320440419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1442892">Donnenfeld et al. (1992)</a>, <a href="#6" class="mim-tip-reference" title="Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J. <strong>Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.</strong> Am. J. Hum. Genet. 67: 197-202, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839976</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10839976[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10839976">Goodman et al. (2000)</a> found that affected members were heterozygous for a 24-bp in-frame insertion in exon 1 at nucleotide 387 of the HOXA13 gene. This insertion occurred in a stretch of 18 imperfect trinucleotide repeats encoding the third of 3 N-terminal polyalanine tracts. It probably had arisen by duplication of repeats 7-14 and expanded the tract from 18 to 26 alanines (8-alanine expansion). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10839976+1442892+2774004" 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 HAND-FOOT-GENITAL SYNDROME</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">rs121912542 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912542;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=rs121912542" 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=rs121912542" 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=RCV000016021" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016021" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016021</a>
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<p>In an isolated case of hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>), <a href="#6" class="mim-tip-reference" title="Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J. <strong>Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.</strong> Am. J. Hum. Genet. 67: 197-202, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839976</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10839976[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10839976">Goodman et al. (2000)</a> identified a heterozygous A-to-C substitution in exon 2 at nucleotide 1114 of the HOXA13 gene, resulting in an asp51-to-his amino acid substitution. The affected individual had severe hand and foot abnormalities, including extremely short thumbs, absent halluces, and marked hypoplasia of all middle phalanges, as well as glanular hypospadias. The authors stated that this was the first missense mutation identified in a human HOX protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10839976" 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 GUTTMACHER SYNDROME (1 family)</strong>
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HOXA13, GLN50LEU AND 2-BP DEL, -79GC, PROMOTER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2115471123 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2115471123;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=rs2115471123" 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=rs2115471123" 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">rs951410939 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs951410939;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=rs951410939" 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=rs951410939" 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=RCV000016022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016022</a>
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<p>In the original family described by <a href="#7" class="mim-tip-reference" title="Guttmacher, A. E. <strong>Autosomal dominant preaxial deficiency, postaxial polydactyly, and hypospadias.</strong> Am. J. Med. Genet. 46: 219-222, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8484413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8484413</a>] [<a href="https://doi.org/10.1002/ajmg.1320460223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8484413">Guttmacher (1993)</a> with preaxial deficiency, postaxial polydactyly, and hypospadias (Guttmacher syndrome; <a href="/entry/176305">176305</a>), <a href="#8" class="mim-tip-reference" title="Innis, J. W., Goodman, F. R., Bacchelli, C., Williams, T. M., Mortlock, D. P., Sateesh, P., Scambler, P. J., McKinnon, W., Guttmacher, A. E. <strong>A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome. (Abstract)</strong> Hum. Mutat. 19: 573-574, 2002."None>Innis et al. (2002)</a> found a novel missense mutation in the HOXA13 homeobox cDNA: an A-to-T transition at position 1112A-T, producing a gln50-to-leu (Q50L) amino acid substitution in the homeodomain of the protein and arising on an allele already carrying a novel 2-bp deletion in the promoter region of the gene. The promoter deletion of GC at position -78 and -79 produces no detectable abnormalities on its own, but was thought to contribute to the phenotype in the affected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8484413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs35861510 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs35861510;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs35861510?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs35861510" 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=rs35861510" 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=RCV001568360" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001568360" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001568360</a>
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<p>In affected members of a family (family 1) with hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>), <a href="#19" class="mim-tip-reference" title="Utsch, B., Becker, K., Brock, D., Lentze, M. J., Bidlingmaier, F., Ludwig, M. <strong>A novel stable polyalanine (poly(A)) expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length?</strong> Hum. Genet. 110: 488-494, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073020</a>] [<a href="https://doi.org/10.1007/s00439-002-0712-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073020">Utsch et al. (2002)</a> found an 18-bp in-frame duplication after nucleotide 376 in exon 1 of the HOXA13 gene, within a cryptic trinucleotide repeat sequence encoding an 18-residue polyalanine tract, resulting in a 6-alanine expansion. The family came to attention because of an affected son admitted to hospital for correction of glanular hypospadias. He showed small hands with short thumbs, brachydactyly of the fifth fingers, and hypoplastic thenar eminences, as well as small feet with short great toes and medially deviated toes. The mother and grandmother showed the same anomalous distal limb findings. Ultrasonography visualized a uterus bicornus unicollis with double cervix in both the mother and grandmother. In addition, the mother showed a longitudinal vaginal septum, explaining the necessity for cesarean section for the birth of both her children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12073020" 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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HOXA13, 27-BP DUP, ALANINE TRACT EXPANSION
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016024" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016024" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016024</a>
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<p>In affected members of a 3-generation family with hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>), <a href="#3" class="mim-tip-reference" title="Debeer, P., Bacchelli, C., Scambler, P. J., De Smet, L., Fryns, J.-P., Goodman, F. R. <strong>Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13.</strong> J. Med. Genet. 39: 852-856, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12414828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12414828</a>] [<a href="https://doi.org/10.1136/jmg.39.11.852" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12414828">Debeer et al. (2002)</a> identified a 27-bp in-frame duplication in the HOXA13 gene, resulting in expansion of the third of the HOXA13 protein's 3 N-terminal polyalanine tracts from 18 to 27 residues (9-alanine expansion). An affected member of this family married a member of another family in which mild synpolydactyly (<a href="/entry/186000">186000</a>) was caused by a missense mutation in the HOXD13 gene (<a href="/entry/142989#0007">142989.0007</a>). The couple produced a girl heterozygous for both mutations who had digital abnormalities strikingly more severe than those in carriers of either individual mutation, indicating that the 2 mutations acted synergistically. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12414828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 HAND-FOOT-GENITAL SYNDROME</strong>
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HOXA13, 42-BP DUP, ALANINE TRACT EXPANSION
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906542 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906542;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=rs387906542" 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=rs387906542" 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=RCV000016025" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016025" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016025</a>
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<p>In a father and daughter with hand-foot-genital syndrome (HFG; <a href="/entry/140000">140000</a>), <a href="#20" class="mim-tip-reference" title="Utsch, B., McCabe, C. D., Galbraith, K., Gonzalez, R., Born, M., Dotsch, J., Ludwig, M., Reutter, H., Innis, J. W. <strong>Molecular characterization of HOXA13 polyalanine expansion proteins in hand-foot-genital syndrome.</strong> Am. J. Med. Genet. 143A: 3161-3168, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935235</a>] [<a href="https://doi.org/10.1002/ajmg.a.31967" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17935235">Utsch et al. (2007)</a> identified a heterozygous 42-bp duplication in the HOXA13 gene, resulting in the addition of 14 alanine residues into polyalanine tract III, which usually has 18 alanine residues. Transient cellular expression studies showed that the expanded protein formed cytoplasmic aggregates that sequestered both wildtype HOXA13 and wildtype HOXD13 (<a href="/entry/142989">142989</a>). The daughter had additional clinical features, including tethered spinal cord with neurogenic bladder and unilateral talipes equinovarus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1093/nar/17.24.10385" target="_blank">Full Text</a>]
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Cooper, K. L., Hu, J. K.-H., ten Berge, D., Fernandez-Teran, M., Ros, M. A., Tabin, C. J.
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[<a href="https://doi.org/10.1126/science.1199499" target="_blank">Full Text</a>]
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<a id="Debeer2002" class="mim-anchor"></a>
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Debeer, P., Bacchelli, C., Scambler, P. J., De Smet, L., Fryns, J.-P., Goodman, F. R.
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<strong>Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13.</strong>
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J. Med. Genet. 39: 852-856, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12414828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12414828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12414828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.39.11.852" target="_blank">Full Text</a>]
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Donnenfeld, A. E., Schrager, D. S., Corson, S. L.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1442892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1442892</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1442892" 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.1320440419" target="_blank">Full Text</a>]
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<a id="Elias1978" class="mim-anchor"></a>
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Elias, S., Simpson, J. L., Feingold, M., Sarto, G. E.
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Fertil. Steril. 29: 239-240, 1978.
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<a id="Goodman2000" class="mim-anchor"></a>
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Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839976</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10839976[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=10839976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/302961" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8484413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8484413</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8484413" 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.1320460223" target="_blank">Full Text</a>]
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<a id="Innis2002" class="mim-anchor"></a>
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Innis, J. W., Goodman, F. R., Bacchelli, C., Williams, T. M., Mortlock, D. P., Sateesh, P., Scambler, P. J., McKinnon, W., Guttmacher, A. E.
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Innis, J. W., Mortlock, D., Chen, Z., Ludwig, M., Williams, M. E., Williams, T. M., Doyle, C. D., Shao, Z., Glynn, M., Mikulic, D., Lehmann, K., Mundlos, S., Utsch, B.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15385446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15385446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15385446" 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/ddh306" target="_blank">Full Text</a>]
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<a id="Kherdjemil2016" class="mim-anchor"></a>
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Kherdjemil, Y., Lalonde, R. L., Sheth, R., Dumouchel, A., de Martino, G., Pineault, K. M., Wellik, D. M., Stadler, H. S., Akimenko, M. A., Kmita, M.
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[<a href="https://doi.org/10.1038/nature19813" target="_blank">Full Text</a>]
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<a id="Mortlock1997" class="mim-anchor"></a>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9020844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9020844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9020844" 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/ng0297-179" target="_blank">Full Text</a>]
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Mortlock, D. P., Post, L. C., Innis, J. W.
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<strong>The molecular basis of hypodactyly (Hd): a deletion in Hoxa13 leads to arrest of digital arch formation.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673126" 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/ng0796-284" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Mortlock1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mortlock, D. P.
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<strong>Personal Communication.</strong>
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Ann Arbor, Mich. 10/31/1996.
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Rinn2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rinn, J. L., Wang, J. K., Allen, N., Brugmann, S. A., Mikels, A. J., Liu, H., Ridky, T. W., Stadler, H. S., Nusse, R., Helms, J. A., Chang, H. Y.
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<strong>A dermal HOX transcriptional program regulates site-specific epidermal fate.</strong>
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Genes Dev. 22: 303-307, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18245445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18245445</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18245445[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=18245445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gad.1610508" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Rosello-Diez2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rosello-Diez, A., Ros, M. A., Torres, M.
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<strong>Diffusible signals, not autonomous mechanisms, determine the main proximodistal limb subdivision.</strong>
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Science 332: 1086-1088, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21617076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21617076</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21617076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1199489" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Roux2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Roux, M., Bouchard, M., Kmita, M.
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<strong>Multifaceted Hoxa13 function in urogenital development underlies the hand-foot-genital syndrome.</strong>
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Hum. Molec. Genet. 28: 1671-1681, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30649340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30649340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30649340" 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/ddz013" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Sheth2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sheth, R., Marcon, L., Bastida, M. F., Junco, M., Quintana, L., Dahn, R., Kmita M., Sharpe, J., Ros, M. A.
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<strong>Hox genes regulate digit patterning by controlling the wavelength of a Turing-type mechanism.</strong>
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Science 338: 1476-1480, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23239739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23239739</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23239739[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=23239739" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1226804" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Stern1970" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stern, A. M., Gall, J. C., Jr., Perry, B. L., Stimson, C. W., Weitkamp, L. R., Poznanski, A. K.
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<strong>The hand-foot-uterus syndrome: a new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract.</strong>
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J. Pediat. 77: 109-116, 1970.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450271</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5450271" 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/s0022-3476(70)80052-x" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Utsch2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Utsch, B., Becker, K., Brock, D., Lentze, M. J., Bidlingmaier, F., Ludwig, M.
|
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<strong>A novel stable polyalanine (poly(A)) expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length?</strong>
|
|
Hum. Genet. 110: 488-494, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073020</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12073020" 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/s00439-002-0712-8" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Utsch2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Utsch, B., McCabe, C. D., Galbraith, K., Gonzalez, R., Born, M., Dotsch, J., Ludwig, M., Reutter, H., Innis, J. W.
|
|
<strong>Molecular characterization of HOXA13 polyalanine expansion proteins in hand-foot-genital syndrome.</strong>
|
|
Am. J. Med. Genet. 143A: 3161-3168, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935235</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935235" 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.31967" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Verp1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Verp, M. S.
|
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<strong>Urinary tract abnormalities in hand-foot-genital syndrome.</strong>
|
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Am. J. Med. Genet. 32: 555 only, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2774004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2774004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2774004" 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.1320320429" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 11/22/2019
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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">
|
|
Ada Hamosh - updated : 08/30/2019<br>Ada Hamosh - updated : 1/14/2013<br>Ada Hamosh - updated : 6/29/2011<br>Cassandra L. Kniffin - updated : 1/12/2009<br>Patricia A. Hartz - updated : 4/28/2008<br>George E. Tiller - updated : 5/22/2007<br>Victor A. McKusick - updated : 5/4/2004<br>Victor A. McKusick - updated : 6/7/2002<br>Victor A. McKusick - updated : 5/14/2002<br>Victor A. McKusick - updated : 9/1/2000<br>Alan F. Scott - updated : 8/21/1995
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 8/22/1990
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 10/31/2023
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/23/2019<br>mgross : 11/22/2019<br>carol : 11/11/2019<br>carol : 11/08/2019<br>alopez : 08/30/2019<br>alopez : 01/16/2013<br>terry : 1/14/2013<br>alopez : 7/19/2011<br>terry : 6/29/2011<br>terry : 9/11/2009<br>wwang : 2/16/2009<br>ckniffin : 1/12/2009<br>alopez : 12/29/2008<br>mgross : 4/28/2008<br>wwang : 5/30/2007<br>terry : 5/22/2007<br>tkritzer : 5/24/2004<br>terry : 5/4/2004<br>terry : 3/18/2004<br>alopez : 6/12/2002<br>terry : 6/7/2002<br>alopez : 5/17/2002<br>terry : 5/14/2002<br>carol : 1/15/2002<br>mcapotos : 12/11/2001<br>terry : 11/29/2001<br>mcapotos : 9/27/2000<br>terry : 9/1/2000<br>dkim : 7/21/1998<br>mark : 8/26/1997<br>mark : 2/2/1997<br>terry : 1/31/1997<br>terry : 1/29/1997<br>terry : 11/22/1996<br>terry : 11/21/1996<br>joanna : 11/7/1996<br>mark : 11/6/1996<br>mark : 10/23/1996<br>mark : 6/27/1996<br>supermim : 3/16/1992<br>carol : 8/22/1990
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
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<strong>*</strong> 142959
|
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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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|
|
HOMEOBOX A13; HOXA13
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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>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
HOMEOBOX 1J; HOX1J
|
|
</span>
|
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</h4>
|
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</div>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: HOXA13</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> 702425002, 722452004;
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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: 7p15.2
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 7:27,194,364-27,200,091 </span>
|
|
</em>
|
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</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">
|
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<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
|
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</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
7p15.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Guttmacher syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
176305
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hand-foot-genital syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
140000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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<div>
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<br />
|
|
</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
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<span class="mim-text-font">
|
|
<p>For background information on homeobox genes, see HOXA7 (142950).</p>
|
|
</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>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
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<span class="mim-text-font">
|
|
<p>Mortlock and Innis (1997) determined the complete coding sequence for HOXA13. </p>
|
|
</span>
|
|
<div>
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<br />
|
|
</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Rinn et al. (2008) stated that fibroblasts obtained from anatomically distinct sites of human skin express genes in a site-specific manner. By microarray analysis of cultured fibroblasts derived from foot or thigh, followed by comparing gene expression profiles of primary fibroblasts from 43 anatomic sites, Rinn et al. (2008) found that HOXA13 expression was associated with distal sites and was required for activation of distal-specific gene expression, including expression of WNT5A (164975). Depletion of HOXA13 in human plantar fibroblasts reduced expression of distal-specific keratin-9 (KRT9; 607606), and KRT9 expression was rescued by addition of recombinant purified WNT5A. In situ hybridization showed that Hoxa13 and Wnt5a were spatially and temporally coexpressed in distal limb bud during mouse development. Rinn et al. (2008) concluded that HOXA13 control of WNT5A expression in distal fibroblasts can regulate site-specific epidermal differentiation. </p><p>Sheth et al. (2012) used mouse genetics to analyze how digit patterning (an iterative digit/nondigit pattern) is generated and showed that the progressive reduction in Hoxa13 and Hoxd11 (142986)-Hoxd13 (142989) genes (hereafter referred to as distal Hox genes) from the Gli3 (165240)-null background results in progressively more severe polydactyly, displaying thinner and densely packed digits. Combined with computer modeling, their results argued for a Turing-type mechanism underlying digit patterning, in which the dose of distal Hox genes modulates the digit period or wavelength. The phenotypic similarity of fish-fin endoskeleton patterns suggested that the pentadactyl state has been achieved through modification of an ancestral Turing-type mechanism. </p><p>Kherdjemil et al. (2016) showed that the mutually exclusive expression of the mouse genes Hoxa11 (142958) and Hoxa13, which had been proposed to be involved in the origin of the tetrapod limb, is required for the pentadactyl state. Kherdjemil et al. (2016) further demonstrated that the exclusion of Hoxa11 from the Hoxa13 domain relies on an enhancer that drives antisense transcription at the Hoxa11 locus after activation by Hoxa13 and Hoxd13. Finally, the authors showed that the enhancer that drives antisense transcription of the mouse Hoxa11 gene is absent in zebrafish, which, together with the largely overlapping expression of hoxa11 and hoxa13 genes reported in fish, suggested that this enhancer emerged in the course of the fin-to-limb transition. On the basis of the polydactyly that was observed after expression of Hoxa11 in distal limbs, Kherdjemil et al. (2016) proposed that the evolution of Hoxa11 regulation contributed to the transition from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant tetrapods. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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|
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<span class="mim-text-font">
|
|
<p>HOXA13 belongs to the cluster of homeobox genes on chromosome 7. As reviewed by Acampora et al. (1989), the homeobox region 1 includes at least 8 homeobox genes in 90 kb of DNA located on chromosome 7. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
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|
|
|
|
<span class="mim-text-font">
|
|
<p>Mortlock (1996) found a mutation in the HOXA13 gene resulting in hand-foot-uterus (HFU) syndrome, also known as hand-foot-genital (HFG) syndrome (140000). Their observations were made in the family reported by Stern et al. (1970). This was the second mutation discovered in a HOX gene as the cause of a malformation; the first to be discovered was the mutation in HOXD13 (142989) as the cause of synpolydactyly (186000). </p><p>Mortlock and Innis (1997) found that affected members of an HFG syndrome family reported by Stern et al. (1970) had a mutation in the HOXA13 gene that converted a highly conserved tryptophan residue in the homeodomain to a stop codon with resulting truncation of 20 amino acids from the protein (142959.0001). It was thought that the mutation probably eliminated or greatly reduced the ability of the protein to bind to DNA. </p><p>Goodman et al. (2000) examined the HOXA13 gene in 2 new and 4 previously reported families with features of HFG syndrome. In 3 families, nonsense mutations truncating the encoded protein N-terminal to or within the homeodomain produced typical limb and genitourinary abnormalities; in the fourth family, an expansion of an N-terminal polyalanine tract produced a similar phenotype; in the fifth family, a missense mutation, which altered an invariant domain, produced an exceptionally severe limb phenotype; and in the sixth family, in which limb abnormalities were atypical, no HOXA13 mutation was detected. </p><p>The polyalanine expansion reported by Goodman et al. (2000) occurred in exon 1 following nucleotide 388 and resulting in the in-frame insertion of 24-bp and an additional 8 alanine residues (142959.0003). Utsch et al. (2002) reported a similar in-frame expansion of 6 alanines also in exon 1, following nucleotide 376, of the HOXA13 gene (142959.0006). They pointed out that expansion by 7 up to 14 alanine residues occurs in the HOXD13 gene, resulting in synpolydactyly. </p><p>Guttmacher syndrome (176305) has a number of features in common with hand-foot-genital syndrome, including hypoplastic thumbs and halluces, fifth-finger clinobrachydactyly, and hypospadias. However, 2 of its features, postaxial polydactyly of the hands and short or uniphalangeal second toes with absent nails, had never been observed in patients with hand-foot-genital syndrome. Because of the similarities, Innis et al. (2002) reinvestigated the family originally described by Guttmacher (1993). They found that affected individuals were heterozygous for a novel missense mutation in the HOXA13 homeobox (Q50L; 142959.0005), which arose on an allele already carrying a novel 2-bp deletion (involving GC at positions -78 and -79) in the gene's highly conserved promoter region. This promoter deletion produces no detectable abnormalities on its own, but may have contributed to the phenotype in the affected individuals. The missense mutation, which altered a key residue in the recognition helix of the homeodomain, is likely to perturb HOXA13's DNA-binding properties, resulting in both a loss and a specific gain of function. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mortlock et al. (1996) found a 50-bp deletion in the first exon of the Hoxa13 gene in mice with the semidominant mutation 'Hypodactyly' (Hd). The mutation was known to map to a genetic interval overlapping the Hoxa cluster on mouse chromosome 6. They stated that the deletion probably arose from unequal recombination between triplet repeats. </p><p>Innis et al. (2004) performed homologous recombination in murine embryonic stem cells to expand the size of the third largest polyalanine tract by 10 residues. Mutant mice were indistinguishable from Hoxa13-null mice. Mutant limb buds had normal steady-state Hoxa13 RNA expression, normal mRNA splicing, and reduced levels of steady-state protein. In vitro translation efficiency of the mutant protein was normal. Innis et al. (2004) concluded that loss of function was secondary to reduced levels of the expanded protein in vivo, likely due to degradation. </p><p>Late limb buds of all tetrapods contain 3 proximodistal segments, each expressing specific homeobox genes. The stylopod (upper limb) expresses Meis1/2 (see 601739), the zeugopod (lower limb) expresses Hoxa11 (142958), and the autopod (hand/foot) Hoxa13, although none of these markers is sufficient to specify limb-segment identity (summary by Rosello-Diez et al., 2011). Cooper et al. (2011) showed that Wnt3a (606359), Fgf8 (600483), and retinoic acid act together to maintain markers of early limb mesenchyme in culture. Rosello-Diez et al. (2011) showed that the first limb bud proximodistal regionalization results from the balance between proximal and distal signals. The results of both groups suggested that retinoic acid is the trunk proximalizing signal and that the trigger for initiating the process of specification of the zeugopod and autopod is the cessation (due to displacement) of retinoic acid exposure, and argued against a mechanism linking proximodistal specification to a cell cycle-based internal clock. </p><p>Roux et al. (2019) found that mice with conditional knockout of Hoxa13 displayed megaureter phenotype due to abnormal ureter insertion caused by defective common nephric duct elimination. The severity of the hydroureter phenotype was likely associated with delayed ureter maturation in Hoxa13 mutant mice. In addition, Hoxa13 mutant mice displayed defective Mullerian duct fusion similar to that found in female patients with HFG syndrome. In situ hybridization analysis revealed that Hoxa13 acted upstream of Ret (164761) and Gata3 (131320) and impacted Ret expression through Gata3. Furthermore, Gata3 played a mediator role on Hoxa13 function in the urogenital sinus. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>8 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 HAND-FOOT-GENITAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HOXA13, TRP369TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894019,
|
|
|
|
|
|
|
|
ClinVar: RCV000016018
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mortlock and Innis (1997) found that patients with the hand-foot-genital syndrome (HFG; 140000) in the family reported by Stern et al. (1970) had an A-to-G transition in a highly conserved tryptophan codon in the HOXA13 homeodomain, which, in addition to causing a trp369-to-ter substitution (TGG to TGA), also destroyed a NlaIV restriction site. The nonsense mutation was predicted to produce a truncated protein missing 20 C-terminal amino acids based on homology to other homeodomains whose 3-dimensional structures had been determined. This portion of the normal homeodomain folds into the last of the 3 alpha-helices. This helix is critical for DNA binding. The authors noted that the tryptophan that was mutated in this family is the only amino acid which is invariant in all known homeodomain proteins. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 HAND-FOOT-GENITAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HOXA13, 407A-C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1158254994,
|
|
|
|
|
|
|
|
ClinVar: RCV000016019
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodman et al. (2000) identified a nonsense truncating mutation in a male patient who had hand and foot abnormalities typical of hand-foot-genital syndrome (HFG; 140000), as well as a short penis tethered inferiorly to the scrotal sac. The predicted truncated protein in this individual lacked the entire homeodomain of the HOXA13 protein. The proband was heterozygous for an A-to-C substitution in exon 1 at base 407 (number of bases starting at the first residue of the initiated codon). The mutation converted a serine residue to a stop codon and was predicted to result in a truncated protein containing only the first 135 amino acids of the wildtype protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 HAND-FOOT-GENITAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HOXA13, 24-BP DUP, ALANINE TRACT EXPANSION
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000016020
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the family (family 4) with hand-foot-genital syndrome (HFG; 140000) in multiple generations reported by Elias et al. (1978), Verp (1989), and Donnenfeld et al. (1992), Goodman et al. (2000) found that affected members were heterozygous for a 24-bp in-frame insertion in exon 1 at nucleotide 387 of the HOXA13 gene. This insertion occurred in a stretch of 18 imperfect trinucleotide repeats encoding the third of 3 N-terminal polyalanine tracts. It probably had arisen by duplication of repeats 7-14 and expanded the tract from 18 to 26 alanines (8-alanine expansion). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HAND-FOOT-GENITAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HOXA13, ASN51HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912542,
|
|
|
|
|
|
|
|
ClinVar: RCV000016021
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an isolated case of hand-foot-genital syndrome (HFG; 140000), Goodman et al. (2000) identified a heterozygous A-to-C substitution in exon 2 at nucleotide 1114 of the HOXA13 gene, resulting in an asp51-to-his amino acid substitution. The affected individual had severe hand and foot abnormalities, including extremely short thumbs, absent halluces, and marked hypoplasia of all middle phalanges, as well as glanular hypospadias. The authors stated that this was the first missense mutation identified in a human HOX protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 GUTTMACHER SYNDROME (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HOXA13, GLN50LEU AND 2-BP DEL, -79GC, PROMOTER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2115471123, rs951410939,
|
|
|
|
|
|
|
|
ClinVar: RCV000016022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the original family described by Guttmacher (1993) with preaxial deficiency, postaxial polydactyly, and hypospadias (Guttmacher syndrome; 176305), Innis et al. (2002) found a novel missense mutation in the HOXA13 homeobox cDNA: an A-to-T transition at position 1112A-T, producing a gln50-to-leu (Q50L) amino acid substitution in the homeodomain of the protein and arising on an allele already carrying a novel 2-bp deletion in the promoter region of the gene. The promoter deletion of GC at position -78 and -79 produces no detectable abnormalities on its own, but was thought to contribute to the phenotype in the affected individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HAND-FOOT-GENITAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HOXA13, 18-BP DUP, ALANINE TRACT EXPANSION
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs35861510,
|
|
|
|
|
|
gnomAD: rs35861510,
|
|
|
|
|
|
ClinVar: RCV001568360
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family (family 1) with hand-foot-genital syndrome (HFG; 140000), Utsch et al. (2002) found an 18-bp in-frame duplication after nucleotide 376 in exon 1 of the HOXA13 gene, within a cryptic trinucleotide repeat sequence encoding an 18-residue polyalanine tract, resulting in a 6-alanine expansion. The family came to attention because of an affected son admitted to hospital for correction of glanular hypospadias. He showed small hands with short thumbs, brachydactyly of the fifth fingers, and hypoplastic thenar eminences, as well as small feet with short great toes and medially deviated toes. The mother and grandmother showed the same anomalous distal limb findings. Ultrasonography visualized a uterus bicornus unicollis with double cervix in both the mother and grandmother. In addition, the mother showed a longitudinal vaginal septum, explaining the necessity for cesarean section for the birth of both her children. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HAND-FOOT-GENITAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
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HOXA13, 27-BP DUP, ALANINE TRACT EXPANSION
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ClinVar: RCV000016024
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<p>In affected members of a 3-generation family with hand-foot-genital syndrome (HFG; 140000), Debeer et al. (2002) identified a 27-bp in-frame duplication in the HOXA13 gene, resulting in expansion of the third of the HOXA13 protein's 3 N-terminal polyalanine tracts from 18 to 27 residues (9-alanine expansion). An affected member of this family married a member of another family in which mild synpolydactyly (186000) was caused by a missense mutation in the HOXD13 gene (142989.0007). The couple produced a girl heterozygous for both mutations who had digital abnormalities strikingly more severe than those in carriers of either individual mutation, indicating that the 2 mutations acted synergistically. </p>
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<h4>
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<strong>.0008 HAND-FOOT-GENITAL SYNDROME</strong>
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</h4>
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<span class="mim-text-font">
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HOXA13, 42-BP DUP, ALANINE TRACT EXPANSION
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SNP: rs387906542,
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ClinVar: RCV000016025
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<p>In a father and daughter with hand-foot-genital syndrome (HFG; 140000), Utsch et al. (2007) identified a heterozygous 42-bp duplication in the HOXA13 gene, resulting in the addition of 14 alanine residues into polyalanine tract III, which usually has 18 alanine residues. Transient cellular expression studies showed that the expanded protein formed cytoplasmic aggregates that sequestered both wildtype HOXA13 and wildtype HOXD13 (142989). The daughter had additional clinical features, including tethered spinal cord with neurogenic bladder and unilateral talipes equinovarus. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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<strong>The human HOX gene family.</strong>
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Cooper, K. L., Hu, J. K.-H., ten Berge, D., Fernandez-Teran, M., Ros, M. A., Tabin, C. J.
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<strong>Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13.</strong>
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Goodman, F. R., Bacchelli, C., Brady, A. F., Brueton, L. A., Fryns, J.-P., Mortlock, D. P., Innis, J. W., Holmes, L. B., Donnenfeld, A. E., Feingold, M., Beemer, F. A., Hennekam, R. C. M., Scambler, P. J.
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Guttmacher, A. E.
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<strong>Autosomal dominant preaxial deficiency, postaxial polydactyly, and hypospadias.</strong>
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Innis, J. W., Goodman, F. R., Bacchelli, C., Williams, T. M., Mortlock, D. P., Sateesh, P., Scambler, P. J., McKinnon, W., Guttmacher, A. E.
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<strong>A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome. (Abstract)</strong>
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Hum. Mutat. 19: 573-574, 2002.
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Innis, J. W., Mortlock, D., Chen, Z., Ludwig, M., Williams, M. E., Williams, T. M., Doyle, C. D., Shao, Z., Glynn, M., Mikulic, D., Lehmann, K., Mundlos, S., Utsch, B.
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<strong>Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model.</strong>
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Kherdjemil, Y., Lalonde, R. L., Sheth, R., Dumouchel, A., de Martino, G., Pineault, K. M., Wellik, D. M., Stadler, H. S., Akimenko, M. A., Kmita, M.
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<strong>Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state.</strong>
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Mortlock, D. P., Post, L. C., Innis, J. W.
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<strong>The molecular basis of hypodactyly (Hd): a deletion in Hoxa13 leads to arrest of digital arch formation.</strong>
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Rinn, J. L., Wang, J. K., Allen, N., Brugmann, S. A., Mikels, A. J., Liu, H., Ridky, T. W., Stadler, H. S., Nusse, R., Helms, J. A., Chang, H. Y.
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<strong>A dermal HOX transcriptional program regulates site-specific epidermal fate.</strong>
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<strong>Urinary tract abnormalities in hand-foot-genital syndrome.</strong>
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[PubMed: 2774004]
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 11/22/2019<br>Ada Hamosh - updated : 08/30/2019<br>Ada Hamosh - updated : 1/14/2013<br>Ada Hamosh - updated : 6/29/2011<br>Cassandra L. Kniffin - updated : 1/12/2009<br>Patricia A. Hartz - updated : 4/28/2008<br>George E. Tiller - updated : 5/22/2007<br>Victor A. McKusick - updated : 5/4/2004<br>Victor A. McKusick - updated : 6/7/2002<br>Victor A. McKusick - updated : 5/14/2002<br>Victor A. McKusick - updated : 9/1/2000<br>Alan F. Scott - updated : 8/21/1995
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 8/22/1990
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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alopez : 10/31/2023<br>carol : 11/23/2019<br>mgross : 11/22/2019<br>carol : 11/11/2019<br>carol : 11/08/2019<br>alopez : 08/30/2019<br>alopez : 01/16/2013<br>terry : 1/14/2013<br>alopez : 7/19/2011<br>terry : 6/29/2011<br>terry : 9/11/2009<br>wwang : 2/16/2009<br>ckniffin : 1/12/2009<br>alopez : 12/29/2008<br>mgross : 4/28/2008<br>wwang : 5/30/2007<br>terry : 5/22/2007<br>tkritzer : 5/24/2004<br>terry : 5/4/2004<br>terry : 3/18/2004<br>alopez : 6/12/2002<br>terry : 6/7/2002<br>alopez : 5/17/2002<br>terry : 5/14/2002<br>carol : 1/15/2002<br>mcapotos : 12/11/2001<br>terry : 11/29/2001<br>mcapotos : 9/27/2000<br>terry : 9/1/2000<br>dkim : 7/21/1998<br>mark : 8/26/1997<br>mark : 2/2/1997<br>terry : 1/31/1997<br>terry : 1/29/1997<br>terry : 11/22/1996<br>terry : 11/21/1996<br>joanna : 11/7/1996<br>mark : 11/6/1996<br>mark : 10/23/1996<br>mark : 6/27/1996<br>supermim : 3/16/1992<br>carol : 8/22/1990
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
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