3241 lines
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3241 lines
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Entry
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- *602427 - T-BOX TRANSCRIPTION FACTOR 6; TBX6
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- OMIM
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<p>
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<span class="h4">*602427</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="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</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/602427">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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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000149922;t=ENST00000395224" 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=6911" 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=602427" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<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=ENSG00000149922;t=ENST00000395224" 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_004608,XM_011545926,XM_047434551,XR_007064904" 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_004608" 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=602427" 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=03888&isoform_id=03888_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/TBX6" 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/4049463,4467813,10433705,18201900,19684004,115502464,119600332,119600333,608785569,608785676,767988749,2217307231,2462550521,2462550523,2462550525,2462550527" 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/O95947" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=6911" 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=ENSG00000149922;t=ENST00000395224" 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=TBX6" 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=TBX6" 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+6911" 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/TBX6" 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:6911" 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/6911" 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=chr16&hgg_gene=ENST00000395224.7&hgg_start=30085793&hgg_end=30091924&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602427[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=602427[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/TBX6/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/ENSG00000149922" 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=TBX6" 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=TBX6" 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=TBX6" 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=TBX6&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/PA36368" 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:11605" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0028789.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:102539" 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/TBX6#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:102539" 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/6911/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=6911" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00004750;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00004750 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00006556;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00006556 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00006557;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00006557 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00006559;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00006559 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-020416-5" 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=TBX6&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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</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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602427
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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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T-BOX TRANSCRIPTION FACTOR 6; TBX6
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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T-BOX 6
|
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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=TBX6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TBX6</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/16/344?start=-3&limit=10&highlight=344">16p11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:30085793-30091924&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'})">16:30,085,793-30,091,924</a> </span>
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</em>
|
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
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<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>
|
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Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
|
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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>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/16/344?start=-3&limit=10&highlight=344">
|
|
16p11.2
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Spondylocostal dysostosis 5
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/122600"> 122600 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</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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|
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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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</tbody>
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</table>
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</div>
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</div>
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<div>
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<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>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/602427" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/602427" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</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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<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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<h4>
|
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|
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<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="cloning" class="mim-anchor"></a>
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<p>Somites, the segmented mesodermal units of the vertebrate embryo, are the precursors of adult skeletal muscle, bone, and cartilage. During embryogenesis, somite progenitor cells ingress through the primitive streak, move laterally to a paraxial position (alongside the body axis), and segment into epithelial somites. <a href="#1" class="mim-tip-reference" title="Chapman, D. L., Agulnik, I., Hancock, S., Silver, L. M., Papaioannou, V. E. <strong>Tbx6, a mouse T-box gene implicated in paraxial mesoderm formation at gastrulation.</strong> Dev. Biol. 180: 534-542, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954725</a>] [<a href="https://doi.org/10.1006/dbio.1996.0326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8954725">Chapman et al. (1996)</a> described a mouse T-box gene, Tbx6, which codes for a putative DNA-binding protein. The embryonic pattern of expression of Tbx6 in somite precursor cells suggested that this gene may be involved in the specification of paraxial mesoderm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8954725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By fluorescence in situ hybridization, <a href="#5" class="mim-tip-reference" title="Papapetrou, C., Putt, W., Fox, M., Edwards, Y. H. <strong>The human TBX6 gene: cloning and assignment to chromosome 16p11.2.</strong> Genomics 55: 238-241, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9933572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9933572</a>] [<a href="https://doi.org/10.1006/geno.1998.5646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9933572">Papapetrou et al. (1999)</a> mapped the human TBX6 gene to 16p11.2. This region of chromosome 16 shows homology of synteny with mouse chromosome 7, cM position 61, the localization reported for the mouse Tbx6 gene (<a href="#1" class="mim-tip-reference" title="Chapman, D. L., Agulnik, I., Hancock, S., Silver, L. M., Papaioannou, V. E. <strong>Tbx6, a mouse T-box gene implicated in paraxial mesoderm formation at gastrulation.</strong> Dev. Biol. 180: 534-542, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954725</a>] [<a href="https://doi.org/10.1006/dbio.1996.0326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8954725">Chapman et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9933572+8954725" 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="#10" class="mim-tip-reference" title="Yasuhiko, Y., Haraguchi, S., Kitajima, S., Takahashi, Y., Kanno, J., Saga, Y. <strong>Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression.</strong> Proc. Nat. Acad. Sci. 103: 3651-3656, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16505380[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508238103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16505380">Yasuhiko et al. (2006)</a> found that Tbx6 was essential for Mesp2 (<a href="/entry/605195">605195</a>) expression during somitogenesis in mouse. Tbx6 directly bound to the Mesp2 gene upstream region and mediated Notch (see <a href="/entry/190198">190198</a>) signaling and subsequent Mesp2 transcription in the anterior presomitic mesoderm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Takemoto, T., Uchikawa, M., Yoshida, M., Bell, D. M., Lovell-Badge, R., Papaioannou, V. E., Kondoh, H. <strong>Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.</strong> Nature 470: 394-398, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21331042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21331042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21331042[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/nature09729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21331042">Takemoto et al. (2011)</a> demonstrated that TBX6-dependent regulation of SOX2 (<a href="/entry/184429">184429</a>) determines the fate of axial stem cells. In wildtype mouse embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate. In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer-N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation into the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a (<a href="/entry/606359">606359</a>) in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wildtype embryos resulted in ectopic neural tube development. Thus, <a href="#8" class="mim-tip-reference" title="Takemoto, T., Uchikawa, M., Yoshida, M., Bell, D. M., Lovell-Badge, R., Papaioannou, V. E., Kondoh, H. <strong>Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.</strong> Nature 470: 394-398, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21331042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21331042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21331042[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/nature09729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21331042">Takemoto et al. (2011)</a> concluded that Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21331042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 3 affected members of a 3-generation Macedonian family with autosomal dominant spondylocostal dysostosis (SCDO5; <a href="/entry/122600">122600</a>), <a href="#7" class="mim-tip-reference" title="Sparrow, D. B., McInerney-Leo, A., Gucev, Z. S., Gardiner, B., Marshall, M., Leo, P. J., Chapman, D. L., Tasic, V., Shishko, A., Brown, M. A., Duncan, E. L., Dunwoodie, S. L. <strong>Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.</strong> Hum. Molec. Genet. 22: 1625-1631, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23335591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23335591</a>] [<a href="https://doi.org/10.1093/hmg/ddt012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23335591">Sparrow et al. (2013)</a> identified heterozygosity for a mutation in the TBX6 gene (<a href="#0001">602427.0001</a>) that segregated with the disease in the family. The mutation disrupts the natural stop codon, resulting in a mutant protein with approximately half the transcriptional activation activity of wildtype TBX6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23335591" 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="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> identified a total of 17 heterozygous TBX6-null mutations in 161 individuals with sporadic congenital scoliosis (11%), and did not observe any null mutations in TBX6 in 166 controls (p less than 3.8 x 10(-6)). These null alleles included copy number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants comprising 1 nonsense (<a href="#0002">602427.0002</a>) and 4 frameshift mutations (see, e.g., <a href="#0004">602427.0004</a>-<a href="#0005">602427.0005</a>). However, dominant inheritance was not supported by the low penetrance of congenital scoliosis in persons carrying the 16p11.2 deletion affecting TBX6. <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> subsequently identified a common TBX6 haplotype (T-C-A; <a href="#0003">602427.0003</a>) as the second risk allele in all 17 affected carriers of TBX6 null mutations (p less than 1.1 x 10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the haplotype functions as a hypomorphic allele. <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> also studied an additional 76 individuals with congenital scoliosis, 6 of whom (8%) had TBX6 compound inheritance (p less than 8.4 x 10(-4)). Finally, in a series of 42 patients with a 16p11.2 deletion, 5 of 6 persons with congenital scoliosis (83%) had the phenotype explained by TBX6 compound inheritance (p = 0.004). All patients were of Han Chinese extraction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25564734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 102 Japanese patients with congenital scoliosis, <a href="#4" class="mim-tip-reference" title="Otomo, N., Takeda, K., Kawai, S., Kou, I., Guo, L., Osawa, M., Alev, C., Kawakami, N., Miyake, N., Matsumoto, N., Yasuhiko, Y., Kotani, T., and 17 others. <strong>Bi-allelic loss of function variants of TBX6 causes (sic) a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.</strong> J. Med. Genet. 56: 622-628, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31015262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31015262</a>] [<a href="https://doi.org/10.1136/jmedgenet-2018-105920" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31015262">Otomo et al. (2019)</a> identified five 16p11.2 deletions (complete loss of TBX6), 1 splice site variant, and 3 missense variants in TBX6; all patients carried the risk haplotype (<a href="#0003">602427.0003</a>) in trans. One of 4 patients with spondylocostal dysostosis had biallelic missense variants in TBX6 (c.356G-A, R119H; c.449G-A, R150H); this patient did not have the risk haplotype on either allele. <a href="#4" class="mim-tip-reference" title="Otomo, N., Takeda, K., Kawai, S., Kou, I., Guo, L., Osawa, M., Alev, C., Kawakami, N., Miyake, N., Matsumoto, N., Yasuhiko, Y., Kotani, T., and 17 others. <strong>Bi-allelic loss of function variants of TBX6 causes (sic) a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.</strong> J. Med. Genet. 56: 622-628, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31015262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31015262</a>] [<a href="https://doi.org/10.1136/jmedgenet-2018-105920" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31015262">Otomo et al. (2019)</a> suggested that biallelic loss-of-function variants of TBX6 cause a spectrum of phenotypes, including CS and SCOD, depending on the severity of the loss of TBX6 function. In vitro functional assays for the missense variants showed that most caused abnormal localization of TBX6 proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31015262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By retrospective analysis, <a href="#6" class="mim-tip-reference" title="Ren, X., Yang, N., Wu, N., Xu, X., Chen, W., Zhang, L., Li, Y., Du, R.-Q., Dong, S., Zhao, S., Chen, S., Jiang, L.-P., Wang, L., Zhang, J., Wu, Z., Jin, L., Qiu, G., Lupski, J. R., Shi, J., Zhang, F., Liu, P. <strong>Increased TBX6 gene dosages induce congenital cervical malformations in humans and mice.</strong> J. Med. Genet. 57: 371-379, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31888956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31888956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31888956[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/10.1136/jmedgenet-2019-106333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31888956">Ren et al. (2020)</a> found that humans who carried the duplicated chromosome 6p11.2 BP4-BP5 region containing TBX6 had increased risk of congenital vertebral malformations (CVMs). Similarly, they found that increased Tbx6 expression in a mouse model was associated with increased incidence of CVMs in cervical vertebrae. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31888956" 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="#2" class="mim-tip-reference" title="Chapman, D. L., Papaioannou, V. E. <strong>Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6.</strong> Nature 391: 695-697, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9490412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9490412</a>] [<a href="https://doi.org/10.1038/35624" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9490412">Chapman and Papaioannou (1998)</a> created a mutation in mouse Tbx6 that profoundly affected the differentiation of paraxial mesoderm. Irregular somites formed in the neck region of mutant embryos, whereas more posterior paraxial tissue did not form somites but instead differentiated along a neural pathway, forming neural-tube-like structures that flanked the axial neural tube. These paraxial tubes showed dorsal/ventral patterning that is characteristic of the neural tube and had differentiated motor neurons. These results indicated that Tbx6 is needed for cells to choose between a mesodermal and a neuronal differentiation pathway during gastrulation; Tbx6 is essential for the specification of posterior paraxial mesoderm, and in its absence cells destined to form posterior somites differentiate along a neuronal pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9490412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Sparrow, D. B., McInerney-Leo, A., Gucev, Z. S., Gardiner, B., Marshall, M., Leo, P. J., Chapman, D. L., Tasic, V., Shishko, A., Brown, M. A., Duncan, E. L., Dunwoodie, S. L. <strong>Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.</strong> Hum. Molec. Genet. 22: 1625-1631, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23335591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23335591</a>] [<a href="https://doi.org/10.1093/hmg/ddt012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23335591">Sparrow et al. (2013)</a> generated Tbx6 +/- mice and studied the vertebral phenotype at embryonic day 14.5. Almost half of the mutant embryos showed a mild cervical or sacral vertebral defect, whereas no defects were seen in wildtype embryos. The cervical defects were restricted to the axis and atlas, and included vertebrae in which the distal part of the spinous process was not attached to the rest of the spinous process, as well as vertebrae in which foramina were present in the most distal portion of the spinous processes. In addition, there were occasional threads of cartilage leading from the spinous process of the axis to the atlas. Similar defects were noted in the sacral vertebrae. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23335591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="/allelicVariants/602427" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602427[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777113 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777113;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=rs587777113" 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=rs587777113" 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=RCV000087033 OR RCV002269823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000087033, RCV002269823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000087033...</a>
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<p>In 3 affected members of a 3-generation Macedonian family segregating autosomal dominant spondylocostal dysostosis (SCDO5; <a href="/entry/122600">122600</a>), originally reported by <a href="#3" class="mim-tip-reference" title="Gucev, Z. S., Tasic, V., Pop-Jordanova, N., Sparrow, D. B., Dunwoodie, S. L., Ellard, S., Young, E., Turnpenny, P. D. <strong>Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: negative mutation analysis of DLL3, MESP2, HES7, and LFNG.</strong> Am. J. Med. Genet. 152A: 1378-1382, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20503311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20503311</a>] [<a href="https://doi.org/10.1002/ajmg.a.33471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20503311">Gucev et al. (2010)</a>, <a href="#7" class="mim-tip-reference" title="Sparrow, D. B., McInerney-Leo, A., Gucev, Z. S., Gardiner, B., Marshall, M., Leo, P. J., Chapman, D. L., Tasic, V., Shishko, A., Brown, M. A., Duncan, E. L., Dunwoodie, S. L. <strong>Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.</strong> Hum. Molec. Genet. 22: 1625-1631, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23335591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23335591</a>] [<a href="https://doi.org/10.1093/hmg/ddt012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23335591">Sparrow et al. (2013)</a> identified heterozygosity for a c.1311A-T transversion in the TBX6 gene, which disrupts the natural stop codon and is predicted to result in the addition of 81 amino acids to the C terminus (Ter437CysextTer81). The mutation was not found in unaffected family members. Transfection studies demonstrated significant impairment of transcriptional activation activity with the TBX6 mutant, to approximately 50% of wildtype activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23335591+20503311" 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> rs201620629 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201620629;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/rs201620629?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=rs201620629" 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=rs201620629" 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=RCV000167862" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000167862" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000167862</a>
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<p>In a 16-year-old Han Chinese female with thoracic and lumbar butterfly vertebrae and right and left thoracic hemivertebrae (SCDO5; <a href="/entry/122600">122600</a>), <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> identified a c.844C-T transition in the TBX6 gene, resulting in an arg282-to-ter (R282X) substitution. On the other allele, the patient carried a hypomorphic haplotype defined by 3 common TBX6 SNPs (see <a href="#0003">602427.0003</a>). This mutation was not observed in any of 166 Han Chinese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25564734" 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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TBX6, HAPLOTYPE, T-C-A (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2289292;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2289292</a>, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3809624;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs3809624</a>, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3809627;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs3809627</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs2289292 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2289292;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/rs2289292?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=rs2289292" 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=rs2289292" 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"><span class="text-primary">●</span> rs3809624 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3809624;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/rs3809624?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=rs3809624" 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=rs3809624" 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"><span class="text-primary">●</span> rs3809627 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3809627;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/rs3809627?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=rs3809627" 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=rs3809627" 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=RCV000167863 OR RCV000242581 OR RCV001521317 OR RCV001672803 OR RCV002244959 OR RCV002248717" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000167863, RCV000242581, RCV001521317, RCV001672803, RCV002244959, RCV002248717" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000167863...</a>
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<p><a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> identified a common haplotype among the Han Chinese characterized by <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2289292;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2289292</a>C-T, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3809624;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs3809624</a>T-C, and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3809627;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs3809627</a>C-A. In vitro luciferase assays in human and mouse cells demonstrated that these SNPs serve as a hypomorphic allele. All 23 persons identified by <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> with TBX6-related congenital scoliosis (SCDO5; <a href="/entry/122600">122600</a>) carried a null allele of TBX6 (frameshift, nonsense, or 16p11.2 deletion) and the T-C-A haplotype on the other allele of TBX6. <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> noted that this haplotype has a prevalence of 44% among Asians. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25564734" 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">rs786204039 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786204039;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=rs786204039" 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=rs786204039" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 7-year-old female with a left lumbar hemivertebra, atrial septal defect, and missing bilateral twelfth ribs (SCDO5; <a href="/entry/122600">122600</a>), <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> identified compound heterozygosity for a frameshift insertion of a T nucleotide in the TBX6 gene (c.1250_1251insT) and the T-C-A haplotype (<a href="#0003">602427.0003</a>). This mutation was not observed in any of 166 Han Chinese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25564734" 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">rs786204040 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786204040;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=rs786204040" 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=rs786204040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 5-year-old male with left hemivertebra between T12 and L1 and a missing right twelfth rib (SCDO5; <a href="/entry/122600">122600</a>), <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> identified compound heterozygosity for a frameshift insertion of a C nucleotide in the TBX6 gene (c.266_267insC) and the T-C-A haplotype (<a href="#0003">602427.0003</a>). This mutation was not observed in any of 166 Han Chinese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25564734" 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> rs202193096 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202193096;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/rs202193096?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=rs202193096" 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=rs202193096" 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=RCV000167866 OR RCV000855736 OR RCV001316105" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000167866, RCV000855736, RCV001316105" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000167866...</a>
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<p>In 3 unrelated individuals of Han Chinese extraction with various vertebral malformations resulting in a diagnosis of congenital scoliosis (SCDO5; <a href="/entry/122600">122600</a>), <a href="#9" class="mim-tip-reference" title="Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others. <strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong> New Eng. J. Med. 372: 341-350, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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/10.1056/NEJMoa1406829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25564734">Wu et al. (2015)</a> identified compound heterozygosity for a c.434C-T transition in the TBX6 gene, resulting in a pro145-to-leu (P145L) substitution, and the T-C-A haplotype (<a href="#0003">602427.0003</a>). In one patient the P145L mutation was shown to be a de novo event. Vertebral malformations included extensive defects of formation and segmentation involving cervical and thoracic vertebrae, hemivertebrae, and butterfly vertebrae. Other congenital malformations included atrial septal bulge, bilateral 13 ribs, missing ribs, and fused ribs. This missense mutation was not identified in the 1000 Genomes Project database, and was suggested to be damaging by at least 3 bioinformatic tools. This mutation was not observed in any of 166 Han Chinese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25564734" 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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Chapman, D. L., Agulnik, I., Hancock, S., Silver, L. M., Papaioannou, V. E.
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<strong>Tbx6, a mouse T-box gene implicated in paraxial mesoderm formation at gastrulation.</strong>
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Dev. Biol. 180: 534-542, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954725</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8954725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/dbio.1996.0326" target="_blank">Full Text</a>]
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Chapman, D. L., Papaioannou, V. E.
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<strong>Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6.</strong>
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Nature 391: 695-697, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9490412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9490412</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9490412" 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/10.1038/35624" target="_blank">Full Text</a>]
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Gucev, Z. S., Tasic, V., Pop-Jordanova, N., Sparrow, D. B., Dunwoodie, S. L., Ellard, S., Young, E., Turnpenny, P. D.
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<strong>Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: negative mutation analysis of DLL3, MESP2, HES7, and LFNG.</strong>
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Am. J. Med. Genet. 152A: 1378-1382, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20503311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20503311</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20503311" 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.33471" 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="4" class="mim-anchor"></a>
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<a id="Otomo2019" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Otomo, N., Takeda, K., Kawai, S., Kou, I., Guo, L., Osawa, M., Alev, C., Kawakami, N., Miyake, N., Matsumoto, N., Yasuhiko, Y., Kotani, T., and 17 others.
|
|
<strong>Bi-allelic loss of function variants of TBX6 causes (sic) a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.</strong>
|
|
J. Med. Genet. 56: 622-628, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31015262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31015262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31015262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2018-105920" 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="5" class="mim-anchor"></a>
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<a id="Papapetrou1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Papapetrou, C., Putt, W., Fox, M., Edwards, Y. H.
|
|
<strong>The human TBX6 gene: cloning and assignment to chromosome 16p11.2.</strong>
|
|
Genomics 55: 238-241, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9933572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9933572</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9933572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1998.5646" 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="6" class="mim-anchor"></a>
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<a id="Ren2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Ren, X., Yang, N., Wu, N., Xu, X., Chen, W., Zhang, L., Li, Y., Du, R.-Q., Dong, S., Zhao, S., Chen, S., Jiang, L.-P., Wang, L., Zhang, J., Wu, Z., Jin, L., Qiu, G., Lupski, J. R., Shi, J., Zhang, F., Liu, P.
|
|
<strong>Increased TBX6 gene dosages induce congenital cervical malformations in humans and mice.</strong>
|
|
J. Med. Genet. 57: 371-379, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31888956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31888956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31888956[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=31888956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1136/jmedgenet-2019-106333" 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="7" class="mim-anchor"></a>
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<a id="Sparrow2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Sparrow, D. B., McInerney-Leo, A., Gucev, Z. S., Gardiner, B., Marshall, M., Leo, P. J., Chapman, D. L., Tasic, V., Shishko, A., Brown, M. A., Duncan, E. L., Dunwoodie, S. L.
|
|
<strong>Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.</strong>
|
|
Hum. Molec. Genet. 22: 1625-1631, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23335591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23335591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23335591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1093/hmg/ddt012" 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="8" class="mim-anchor"></a>
|
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<a id="Takemoto2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Takemoto, T., Uchikawa, M., Yoshida, M., Bell, D. M., Lovell-Badge, R., Papaioannou, V. E., Kondoh, H.
|
|
<strong>Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.</strong>
|
|
Nature 470: 394-398, 2011.
|
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21331042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21331042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21331042[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=21331042" 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/nature09729" 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="9" class="mim-anchor"></a>
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<a id="Wu2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others.
|
|
<strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong>
|
|
New Eng. J. Med. 372: 341-350, 2015.
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25564734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25564734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25564734[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=25564734" 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/10.1056/NEJMoa1406829" 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="10" class="mim-anchor"></a>
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<a id="Yasuhiko2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Yasuhiko, Y., Haraguchi, S., Kitajima, S., Takahashi, Y., Kanno, J., Saga, Y.
|
|
<strong>Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 3651-3656, 2006.
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16505380[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=16505380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1073/pnas.0508238103" 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 : 12/11/2020
|
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 10/12/2020<br>Ada Hamosh - updated : 3/26/2015<br>Marla J. F. O'Neill - updated : 2/18/2014<br>Ada Hamosh - updated : 6/29/2011<br>Patricia A. Hartz - updated : 7/30/2007<br>Carol A. Bocchini - updated : 3/7/1999
|
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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">
|
|
Victor A. McKusick : 3/9/1998
|
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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>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
alopez : 07/15/2024
|
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</span>
|
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</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<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">
|
|
mgross : 01/12/2021<br>mgross : 12/11/2020<br>carol : 10/12/2020<br>carol : 03/23/2020<br>alopez : 03/27/2015<br>alopez : 3/26/2015<br>carol : 2/18/2014<br>mcolton : 2/17/2014<br>alopez : 7/5/2011<br>terry : 6/29/2011<br>mgross : 7/30/2007<br>terry : 7/30/2007<br>carol : 2/25/2000<br>terry : 3/9/1999<br>carol : 3/7/1999<br>alopez : 2/25/1999<br>alopez : 3/9/1998
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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">
|
|
<strong>*</strong> 602427
|
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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>
|
|
<span class="mim-font">
|
|
|
|
T-BOX TRANSCRIPTION FACTOR 6; TBX6
|
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</span>
|
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</h3>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
T-BOX 6
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: TBX6</em></strong>
|
|
</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>
|
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<em>
|
|
Cytogenetic location: 16p11.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 16:30,085,793-30,091,924 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
16p11.2
|
|
</span>
|
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</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Spondylocostal dysostosis 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
122600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
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|
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</tr>
|
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|
|
|
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</tbody>
|
|
</table>
|
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</div>
|
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</div>
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<div>
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<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
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<span class="mim-text-font">
|
|
<p>Somites, the segmented mesodermal units of the vertebrate embryo, are the precursors of adult skeletal muscle, bone, and cartilage. During embryogenesis, somite progenitor cells ingress through the primitive streak, move laterally to a paraxial position (alongside the body axis), and segment into epithelial somites. Chapman et al. (1996) described a mouse T-box gene, Tbx6, which codes for a putative DNA-binding protein. The embryonic pattern of expression of Tbx6 in somite precursor cells suggested that this gene may be involved in the specification of paraxial mesoderm. </p>
|
|
</span>
|
|
<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>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By fluorescence in situ hybridization, Papapetrou et al. (1999) mapped the human TBX6 gene to 16p11.2. This region of chromosome 16 shows homology of synteny with mouse chromosome 7, cM position 61, the localization reported for the mouse Tbx6 gene (Chapman et al., 1996). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Yasuhiko et al. (2006) found that Tbx6 was essential for Mesp2 (605195) expression during somitogenesis in mouse. Tbx6 directly bound to the Mesp2 gene upstream region and mediated Notch (see 190198) signaling and subsequent Mesp2 transcription in the anterior presomitic mesoderm. </p><p>Takemoto et al. (2011) demonstrated that TBX6-dependent regulation of SOX2 (184429) determines the fate of axial stem cells. In wildtype mouse embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate. In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer-N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation into the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a (606359) in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wildtype embryos resulted in ectopic neural tube development. Thus, Takemoto et al. (2011) concluded that Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 3 affected members of a 3-generation Macedonian family with autosomal dominant spondylocostal dysostosis (SCDO5; 122600), Sparrow et al. (2013) identified heterozygosity for a mutation in the TBX6 gene (602427.0001) that segregated with the disease in the family. The mutation disrupts the natural stop codon, resulting in a mutant protein with approximately half the transcriptional activation activity of wildtype TBX6. </p><p>Wu et al. (2015) identified a total of 17 heterozygous TBX6-null mutations in 161 individuals with sporadic congenital scoliosis (11%), and did not observe any null mutations in TBX6 in 166 controls (p less than 3.8 x 10(-6)). These null alleles included copy number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants comprising 1 nonsense (602427.0002) and 4 frameshift mutations (see, e.g., 602427.0004-602427.0005). However, dominant inheritance was not supported by the low penetrance of congenital scoliosis in persons carrying the 16p11.2 deletion affecting TBX6. Wu et al. (2015) subsequently identified a common TBX6 haplotype (T-C-A; 602427.0003) as the second risk allele in all 17 affected carriers of TBX6 null mutations (p less than 1.1 x 10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the haplotype functions as a hypomorphic allele. Wu et al. (2015) also studied an additional 76 individuals with congenital scoliosis, 6 of whom (8%) had TBX6 compound inheritance (p less than 8.4 x 10(-4)). Finally, in a series of 42 patients with a 16p11.2 deletion, 5 of 6 persons with congenital scoliosis (83%) had the phenotype explained by TBX6 compound inheritance (p = 0.004). All patients were of Han Chinese extraction. </p><p>Among 102 Japanese patients with congenital scoliosis, Otomo et al. (2019) identified five 16p11.2 deletions (complete loss of TBX6), 1 splice site variant, and 3 missense variants in TBX6; all patients carried the risk haplotype (602427.0003) in trans. One of 4 patients with spondylocostal dysostosis had biallelic missense variants in TBX6 (c.356G-A, R119H; c.449G-A, R150H); this patient did not have the risk haplotype on either allele. Otomo et al. (2019) suggested that biallelic loss-of-function variants of TBX6 cause a spectrum of phenotypes, including CS and SCOD, depending on the severity of the loss of TBX6 function. In vitro functional assays for the missense variants showed that most caused abnormal localization of TBX6 proteins. </p><p>By retrospective analysis, Ren et al. (2020) found that humans who carried the duplicated chromosome 6p11.2 BP4-BP5 region containing TBX6 had increased risk of congenital vertebral malformations (CVMs). Similarly, they found that increased Tbx6 expression in a mouse model was associated with increased incidence of CVMs in cervical vertebrae. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Chapman and Papaioannou (1998) created a mutation in mouse Tbx6 that profoundly affected the differentiation of paraxial mesoderm. Irregular somites formed in the neck region of mutant embryos, whereas more posterior paraxial tissue did not form somites but instead differentiated along a neural pathway, forming neural-tube-like structures that flanked the axial neural tube. These paraxial tubes showed dorsal/ventral patterning that is characteristic of the neural tube and had differentiated motor neurons. These results indicated that Tbx6 is needed for cells to choose between a mesodermal and a neuronal differentiation pathway during gastrulation; Tbx6 is essential for the specification of posterior paraxial mesoderm, and in its absence cells destined to form posterior somites differentiate along a neuronal pathway. </p><p>Sparrow et al. (2013) generated Tbx6 +/- mice and studied the vertebral phenotype at embryonic day 14.5. Almost half of the mutant embryos showed a mild cervical or sacral vertebral defect, whereas no defects were seen in wildtype embryos. The cervical defects were restricted to the axis and atlas, and included vertebrae in which the distal part of the spinous process was not attached to the rest of the spinous process, as well as vertebrae in which foramina were present in the most distal portion of the spinous processes. In addition, there were occasional threads of cartilage leading from the spinous process of the axis to the atlas. Similar defects were noted in the sacral vertebrae. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 SPONDYLOCOSTAL DYSOSTOSIS 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBX6, TER437CYS
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<br />
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SNP: rs587777113,
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ClinVar: RCV000087033, RCV002269823
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected members of a 3-generation Macedonian family segregating autosomal dominant spondylocostal dysostosis (SCDO5; 122600), originally reported by Gucev et al. (2010), Sparrow et al. (2013) identified heterozygosity for a c.1311A-T transversion in the TBX6 gene, which disrupts the natural stop codon and is predicted to result in the addition of 81 amino acids to the C terminus (Ter437CysextTer81). The mutation was not found in unaffected family members. Transfection studies demonstrated significant impairment of transcriptional activation activity with the TBX6 mutant, to approximately 50% of wildtype activity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 SPONDYLOCOSTAL DYSOSTOSIS 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBX6, ARG282TER
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<br />
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SNP: rs201620629,
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gnomAD: rs201620629,
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ClinVar: RCV000167862
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 16-year-old Han Chinese female with thoracic and lumbar butterfly vertebrae and right and left thoracic hemivertebrae (SCDO5; 122600), Wu et al. (2015) identified a c.844C-T transition in the TBX6 gene, resulting in an arg282-to-ter (R282X) substitution. On the other allele, the patient carried a hypomorphic haplotype defined by 3 common TBX6 SNPs (see 602427.0003). This mutation was not observed in any of 166 Han Chinese controls. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 SPONDYLOCOSTAL DYSOSTOSIS 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBX6, HAPLOTYPE, T-C-A ({dbSNP rs2289292}, {dbSNP rs3809624}, {dbSNP rs3809627})
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<br />
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SNP: rs2289292, rs3809624, rs3809627,
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gnomAD: rs2289292, rs3809624, rs3809627,
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ClinVar: RCV000167863, RCV000242581, RCV001521317, RCV001672803, RCV002244959, RCV002248717
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Wu et al. (2015) identified a common haplotype among the Han Chinese characterized by rs2289292C-T, rs3809624T-C, and rs3809627C-A. In vitro luciferase assays in human and mouse cells demonstrated that these SNPs serve as a hypomorphic allele. All 23 persons identified by Wu et al. (2015) with TBX6-related congenital scoliosis (SCDO5; 122600) carried a null allele of TBX6 (frameshift, nonsense, or 16p11.2 deletion) and the T-C-A haplotype on the other allele of TBX6. Wu et al. (2015) noted that this haplotype has a prevalence of 44% among Asians. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 SPONDYLOCOSTAL DYSOSTOSIS 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBX6, 1-BP INS, 1250T
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<br />
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SNP: rs786204039,
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ClinVar: RCV000167864
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 7-year-old female with a left lumbar hemivertebra, atrial septal defect, and missing bilateral twelfth ribs (SCDO5; 122600), Wu et al. (2015) identified compound heterozygosity for a frameshift insertion of a T nucleotide in the TBX6 gene (c.1250_1251insT) and the T-C-A haplotype (602427.0003). This mutation was not observed in any of 166 Han Chinese controls. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 SPONDYLOCOSTAL DYSOSTOSIS 5</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBX6, 1-BP INS, 266C
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<br />
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SNP: rs786204040,
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ClinVar: RCV000167865
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 5-year-old male with left hemivertebra between T12 and L1 and a missing right twelfth rib (SCDO5; 122600), Wu et al. (2015) identified compound heterozygosity for a frameshift insertion of a C nucleotide in the TBX6 gene (c.266_267insC) and the T-C-A haplotype (602427.0003). This mutation was not observed in any of 166 Han Chinese controls. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SPONDYLOCOSTAL DYSOSTOSIS 5</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
TBX6, PRO145LEU
|
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<br />
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SNP: rs202193096,
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gnomAD: rs202193096,
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|
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ClinVar: RCV000167866, RCV000855736, RCV001316105
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated individuals of Han Chinese extraction with various vertebral malformations resulting in a diagnosis of congenital scoliosis (SCDO5; 122600), Wu et al. (2015) identified compound heterozygosity for a c.434C-T transition in the TBX6 gene, resulting in a pro145-to-leu (P145L) substitution, and the T-C-A haplotype (602427.0003). In one patient the P145L mutation was shown to be a de novo event. Vertebral malformations included extensive defects of formation and segmentation involving cervical and thoracic vertebrae, hemivertebrae, and butterfly vertebrae. Other congenital malformations included atrial septal bulge, bilateral 13 ribs, missing ribs, and fused ribs. This missense mutation was not identified in the 1000 Genomes Project database, and was suggested to be damaging by at least 3 bioinformatic tools. This mutation was not observed in any of 166 Han Chinese controls. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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|
</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Chapman, D. L., Agulnik, I., Hancock, S., Silver, L. M., Papaioannou, V. E.
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<strong>Tbx6, a mouse T-box gene implicated in paraxial mesoderm formation at gastrulation.</strong>
|
|
Dev. Biol. 180: 534-542, 1996.
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[PubMed: 8954725]
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[Full Text: https://doi.org/10.1006/dbio.1996.0326]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chapman, D. L., Papaioannou, V. E.
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<strong>Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6.</strong>
|
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Nature 391: 695-697, 1998.
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[PubMed: 9490412]
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[Full Text: https://doi.org/10.1038/35624]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gucev, Z. S., Tasic, V., Pop-Jordanova, N., Sparrow, D. B., Dunwoodie, S. L., Ellard, S., Young, E., Turnpenny, P. D.
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|
<strong>Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: negative mutation analysis of DLL3, MESP2, HES7, and LFNG.</strong>
|
|
Am. J. Med. Genet. 152A: 1378-1382, 2010.
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[PubMed: 20503311]
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[Full Text: https://doi.org/10.1002/ajmg.a.33471]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Otomo, N., Takeda, K., Kawai, S., Kou, I., Guo, L., Osawa, M., Alev, C., Kawakami, N., Miyake, N., Matsumoto, N., Yasuhiko, Y., Kotani, T., and 17 others.
|
|
<strong>Bi-allelic loss of function variants of TBX6 causes (sic) a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.</strong>
|
|
J. Med. Genet. 56: 622-628, 2019.
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[PubMed: 31015262]
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[Full Text: https://doi.org/10.1136/jmedgenet-2018-105920]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Papapetrou, C., Putt, W., Fox, M., Edwards, Y. H.
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<strong>The human TBX6 gene: cloning and assignment to chromosome 16p11.2.</strong>
|
|
Genomics 55: 238-241, 1999.
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[PubMed: 9933572]
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[Full Text: https://doi.org/10.1006/geno.1998.5646]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ren, X., Yang, N., Wu, N., Xu, X., Chen, W., Zhang, L., Li, Y., Du, R.-Q., Dong, S., Zhao, S., Chen, S., Jiang, L.-P., Wang, L., Zhang, J., Wu, Z., Jin, L., Qiu, G., Lupski, J. R., Shi, J., Zhang, F., Liu, P.
|
|
<strong>Increased TBX6 gene dosages induce congenital cervical malformations in humans and mice.</strong>
|
|
J. Med. Genet. 57: 371-379, 2020.
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[PubMed: 31888956]
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[Full Text: https://doi.org/10.1136/jmedgenet-2019-106333]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sparrow, D. B., McInerney-Leo, A., Gucev, Z. S., Gardiner, B., Marshall, M., Leo, P. J., Chapman, D. L., Tasic, V., Shishko, A., Brown, M. A., Duncan, E. L., Dunwoodie, S. L.
|
|
<strong>Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.</strong>
|
|
Hum. Molec. Genet. 22: 1625-1631, 2013.
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[PubMed: 23335591]
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[Full Text: https://doi.org/10.1093/hmg/ddt012]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Takemoto, T., Uchikawa, M., Yoshida, M., Bell, D. M., Lovell-Badge, R., Papaioannou, V. E., Kondoh, H.
|
|
<strong>Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.</strong>
|
|
Nature 470: 394-398, 2011.
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[PubMed: 21331042]
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[Full Text: https://doi.org/10.1038/nature09729]
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Wu, N., Ming, X., Xiao, J., Wu, Z., Chen, X., Shinawi, M., Shen, Y., Yu, G., Liu, J., Xie, H., Gucev, Z. S., Liu, S., and 46 others.
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<strong>TBX6 null variants and a common hypomorphic allele in congenital scoliosis.</strong>
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New Eng. J. Med. 372: 341-350, 2015.
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[PubMed: 25564734]
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[Full Text: https://doi.org/10.1056/NEJMoa1406829]
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Yasuhiko, Y., Haraguchi, S., Kitajima, S., Takahashi, Y., Kanno, J., Saga, Y.
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<strong>Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression.</strong>
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Proc. Nat. Acad. Sci. 103: 3651-3656, 2006.
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[PubMed: 16505380]
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[Full Text: https://doi.org/10.1073/pnas.0508238103]
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Bao Lige - updated : 12/11/2020<br>Sonja A. Rasmussen - updated : 10/12/2020<br>Ada Hamosh - updated : 3/26/2015<br>Marla J. F. O'Neill - updated : 2/18/2014<br>Ada Hamosh - updated : 6/29/2011<br>Patricia A. Hartz - updated : 7/30/2007<br>Carol A. Bocchini - updated : 3/7/1999
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Victor A. McKusick : 3/9/1998
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