3181 lines
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Entry
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- #122600 - SPONDYLOCOSTAL DYSOSTOSIS 5; SCDO5
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- OMIM
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<p>
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<span class="h4">#122600</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/122600"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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<a href="/phenotypicSeries/PS277300"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#nomenclature">Nomenclature</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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</a>
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</span>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=SPONDYLOCOSTAL DYSOSTOSIS" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=2841&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK8828/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/6805" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=122600[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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1797" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/2b57d491-0920-4259-941f-d58f4255b482/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="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/disease/DOID:0112363" 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="http://www.informatics.jax.org/disease/122600" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0112363" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></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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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 1797<br />
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<strong>DO:</strong> 0112363<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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122600
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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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SPONDYLOCOSTAL DYSOSTOSIS 5; SCDO5
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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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SCOLIOSIS, CONGENITAL, WITH OR WITHOUT RIB ANOMALIES<br />
|
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TACS<br />
|
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SPONDYLOCOSTAL DYSPLASIA<br />
|
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SPONDYLOTHORACIC DYSOSTOSIS<br />
|
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COSTOVERTEBRAL SEGMENTATION ANOMALIES
|
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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="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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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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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/16/344?start=-3&limit=10&highlight=344">
|
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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">
|
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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">
|
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<a href="/entry/122600"> 122600 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="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>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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TBX6
|
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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/602427"> 602427 </a>
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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 ">
|
|
<a href="/clinicalSynopsis/122600" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
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|
<div class="btn-group">
|
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|
|
<a href="/phenotypicSeries/PS277300" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
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</div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/122600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/122600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
|
</div>
|
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|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br /> -
|
|
Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Height </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Short stature, disproportionate (short trunk) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846435&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846435</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003521" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003521</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/772086000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">772086000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003498" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003498</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Neck </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Short neck (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95427009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95427009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Neck,Short-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CHEST </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Ribs Sternum Clavicles & Scapulae </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pectus carinatum (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205101001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205101001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38774000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38774000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.82</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2939416&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2939416</a>, <a href="https://bioportal.bioontology.org/search?q=C0158731&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158731</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000768" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000768</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000768" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000768</a>]</span><br /> -
|
|
Rib abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842083&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842083</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000772</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000772</a>]</span><br /> -
|
|
Fused ribs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/66102006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">66102006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265695&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265695</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000902" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000902</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000902" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000902</a>]</span><br /> -
|
|
Extra ribs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205460009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205460009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0345397&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0345397</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005815" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005815</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005815" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005815</a>]</span><br /> -
|
|
Missing ribs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249695006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249695006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426816</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000921" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000921</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000921" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000921</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br /> -
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Hemivertebrae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68359008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68359008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.49" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.49</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/756.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">756.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265677&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265677</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002937</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002937</a>]</span><br /> -
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Butterfly vertebrae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/897560004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">897560004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5438458&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5438458</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003316</a>]</span><br /> -
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Fused vertebrae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849073&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849073</a>]</span><br /> -
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Syringomyelia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192894009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192894009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111496009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111496009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G95.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G95.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/336.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">336.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0039144&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039144</a>, <a href="https://bioportal.bioontology.org/search?q=C0039145&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039145</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003396</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003396</a>]</span><br />
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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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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Intrafamilial variability of features<br /> -
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A risk haplotype (<a href="/entry/602427#0003">602427.0003</a>) in addition to a null mutation is present in most patients<br />
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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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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the T-box 6 gene (TBX6, <a href="/entry/602427#0001">602427.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<h5>
|
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Spondylocostal dysostosis
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- <a href="/phenotypicSeries/PS277300">PS277300</a>
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- 6 Entries
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</h5>
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
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<thead>
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<tr>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Location</strong>
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</th>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
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<strong>Phenotype</strong>
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Inheritance</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />mapping key</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
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</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
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</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/678?start=-3&limit=10&highlight=678"> 6q14.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616566"> ?Spondylocostal dysostosis 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616566"> 616566 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609891"> RIPPLY2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609891"> 609891 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/27?start=-3&limit=10&highlight=27"> 7p22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609813"> Spondylocostal dysostosis 3, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609813"> 609813 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602576"> LFNG </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602576"> 602576 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/15/508?start=-3&limit=10&highlight=508"> 15q26.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608681"> Spondylocostal dysostosis 2, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608681"> 608681 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605195"> MESP2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605195"> 605195 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/16/344?start=-3&limit=10&highlight=344"> 16p11.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/122600"> Spondylocostal dysostosis 5 </a>
|
|
</span>
|
|
</td>
|
|
<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>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/122600"> 122600 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602427"> TBX6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602427"> 602427 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/193?start=-3&limit=10&highlight=193"> 17p13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613686"> Spondylocostal dysostosis 4, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613686"> 613686 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608059"> HES7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608059"> 608059 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/685?start=-3&limit=10&highlight=685"> 19q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/277300"> Spondylocostal dysostosis 1, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>A number sign (#) is used with this entry because of evidence that spondylocostal dysostosis-5 (SCDO5) is caused by heterozygous or compound heterozygous mutation in the TBX6 gene (<a href="/entry/602427">602427</a>) on chromosome 16p11.</p><p>For a general phenotypic description and a discussion of genetic heterogeneity of spondylocostal dysostosis, see SCDO1 (<a href="/entry/277300">277300</a>).</p>
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<p><a href="#8" class="mim-tip-reference" title="Rimoin, D. L., Fletcher, B. D., McKusick, V. A. <strong>Spondylocostal dysplasia: a dominantly inherited form of short-trunked dwarfism.</strong> Am. J. Med. 45: 948-953, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5722643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5722643</a>] [<a href="https://doi.org/10.1016/0002-9343(68)90193-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5722643">Rimoin et al. (1968)</a> reported a family in which father and son and probably 2 preceding generations were short of stature (less than 5 feet), the shortening being mainly in the trunk, and had multiple rib and vertebral anomalies. The number of ribs was reduced to 11 and several ribs were fused posteriorly. Hemivertebra and vertebral fusion were noted at multiple levels in the cervical and thoracic spine. No neurologic manifestations were present. <a href="#4" class="mim-tip-reference" title="Langer, L. O., Jr. <strong>Personal Communication.</strong> Minneapolis, Minn. 1967."None>Langer (1967)</a> reported another family with multiple affected generations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5722643" 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="Ruett, A., Degenhardt, K.-H. <strong>Beitrag zur Aetiologie und Pathogenese von Wirbelsaeulenmissbildungen.</strong> Arch. Orthop. Unfallchir. 51: 120-139, 1959. Note: See Also: Becker, P. E. (ed.): Ein kurzes Handbuch in fuenf Baenden. Vol. 2. Stuttgart: Georg Thieme Verlag, 1964. P. 589.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14440060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14440060</a>] [<a href="https://doi.org/10.1007/BF00415439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14440060">Ruett and Degenhardt (1959)</a> described a 4-generation family (Familie Mck.) in which 4 individuals had congenital scoliosis. <a href="#14" class="mim-tip-reference" title="Van der Sar, A. <strong>Hereditary multiple hemivertebrae.</strong> Doc. Med. Geogr. Trop. 4: 23-28, 1952."None>Van der Sar (1952)</a> found multiple hemivertebrae and rib anomalies in a mother and daughter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14440060" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ayme, S., Preus, M. <strong>Spondylocostal/spondylothoracic dysostosis: the clinical basis for prognosticating and genetic counseling.</strong> Am. J. Med. Genet. 24: 599-606, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3740094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3740094</a>] [<a href="https://doi.org/10.1002/ajmg.1320240403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3740094">Ayme and Preus (1986)</a> did a cluster analysis on reported cases of spondylocostal dysostosis, spondylothoracic dysplasia, and Jarcho-Levin syndrome. They concluded that the dominant and mild recessive forms of spondylothoracic dysplasia, falling into their cluster 2, could not be distinguished. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3740094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The family with affected members in 3 generations reported by <a href="#12" class="mim-tip-reference" title="Temple, I. K., Thomas, T. G., Baraitser, M. <strong>Congenital spinal deformity in a three generation family.</strong> J. Med. Genet. 25: 831-834, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3236365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3236365</a>] [<a href="https://doi.org/10.1136/jmg.25.12.831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3236365">Temple et al. (1988)</a> may have had the same condition as that reported by <a href="#8" class="mim-tip-reference" title="Rimoin, D. L., Fletcher, B. D., McKusick, V. A. <strong>Spondylocostal dysplasia: a dominantly inherited form of short-trunked dwarfism.</strong> Am. J. Med. 45: 948-953, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5722643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5722643</a>] [<a href="https://doi.org/10.1016/0002-9343(68)90193-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5722643">Rimoin et al. (1968)</a> and others. Short stature was striking. The rib changes were only mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3236365+5722643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Lorenz, P., Rupprecht, E. <strong>Spondylocostal dysostosis: dominant type.</strong> Am. J. Med. Genet. 35: 219-221, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309760</a>] [<a href="https://doi.org/10.1002/ajmg.1320350215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2309760">Lorenz and Rupprecht (1990)</a> reported the cases of a father and daughter. Abnormality of the ribs was more severe in the infant daughter than usual in this form and was suggestive of the changes found in the autosomal recessive type. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2309760" 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="#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> studied an indigenous 3-generation Macedonian family segregating autosomal dominant spondylocostal dysostosis. The 12-year-old proband and his father and paternal uncle had disproportionately short trunks and necks with a normal range of movement, and radiographs revealed mild scoliosis with a mixture of hemivertebrae and vertebral blocks. The ribs were relatively mildly affected, with nearly normal alignment and a possible point of fusion high on the left posteriorly in the proband and mild thoracic sulci and flaring of the lower rib cage in the father and uncle. There were no other significant organ abnormalities, no obvious dysmorphic features, and neurodevelopment was normal. The paternal grandfather was deceased but was reported to have had the same phenotype. <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'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="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> reported 23 Han Chinese individuals with a diagnosis of congenital scoliosis that was related to compound heterozygous mutation in the TBX6 gene. All 23 individuals had 1 or more hemivertebrae. The number of hemivertebrae was significantly higher in patients with TBX6-related congenital scoliosis that in those with congenital scoliosis without TBX6 mutation. Rib abnormalities were also reported in most patients. <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><a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a> studied cohorts of patients with congenital scoliosis (CS), 345 from China (cohort 1), 142 from Japan (cohort 2), and 10 from the United States (cohort 3). Clinically measurable endophenotypes were compared according to the TBX6 genotypes. <a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a> developed a clinical diagnostic algorithm (TACScore) to assist in clinical recognition of TBX6-associated CS (TACS). Cohort 1 included 33 TACS patients, and these were significantly younger at onset (median age 2 years) than the remaining CS patients (median age 3 years), presented with 1 or more hemivertebrae/butterfly vertebrae, and exhibited vertebral malformations involving the lower part of the spine (T8-S5); observations were confirmed in Japanese and US cohorts. Simple rib anomalies were prevalent in the TACS patients (present in 25 of 33) whereas intraspinal anomalies were uncommon (present in only 1 patient). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30636772" 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="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> described 9 Japanese patients with congenital scoliosis with involvement of cervical thoracic and lumbar vertebral areas. Vertebral anomalies (blocked vertebrae, hemivertebrae, and butterfly vertebrae) were seen in all patients, with 3 patients also having rib anomalies. A Japanese patient with SCOD had multiple defects along the spine and multiple posterior fusions of the ribs. <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>
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<p>The inheritance pattern of spondylocostal dysostosis-5 can be autosomal dominant (<a href="#10" 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>) or autosomal recessive (<a href="#15" 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>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23335591+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><a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a> pointed out that SCDO5 does not follow conventional rare variant mendelian inheritance expectations, likely reflecting the embryonic lethality of TBX6 homozygous null alleles. Instead, SCDO5 is caused by biallelic variants at a locus, consistent with autosomal recessive trait manifestation, but with the presence of a single rare loss-of-function variant in trans with one common hypomorphic allele; a gene dosage that is less than haploinsufficiency but not 0, as with homozygous null alleles. <a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a> suggested that this genetic model (compound inheritance and TACS) may provide an explanation for scenarios in which monoallelic variants and phenotypes are perceived to be following a dominant inheritance pattern, but for a disease trait with incomplete penetrance, or in which the disease pattern observed is pseudodominance, as found when the carrier state occurs at a high frequency in the population. Because the T-C-A haplotype is common worldwide (44% among Asians and 33% among Europeans, but less than 1% among Africans), the haplotype is likely to be parsed and filtered out by genomic analytical pipelines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30636772" 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>Polydysspondyly was described by <a href="#13" class="mim-tip-reference" title="Turpin, R., Lejeune, J., Lafourcade, J., Gautier, M. <strong>Aberrations chromosomiques et maladies humaines. La polydysspondylie a 45 chromosomes.</strong> C. R. Hebd Seances Acad. Sci. 248: 3636-3638, 1959. Note: Formerly Comp. Rend. Acad. Sci. (Paris).[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13671780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13671780</a>]" pmid="13671780">Turpin et al. (1959)</a> in association with a translocation involving group D and G chromosomes. <a href="#2" class="mim-tip-reference" title="de Grouchy, J., Mlynarski, J. C., Maroteaux, P., Lamy, M., Deshaies, G., Benichou, C., Salmon, C. <strong>Syndrome polydysspondylique par translocation 14-15 et dyschondrosteose chez un meme sujet. Segregation familiale.</strong> C. R. Hebd. Seances Acad. Sci. 256: 1614-1616, 1963.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13950852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13950852</a>]" pmid="13950852">De Grouchy et al. (1963)</a> reported a similar condition in mother and daughter, both of whom carried a 14-15 translocation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13950852+13671780" 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 and 2 unaffected members of a 3-generation Macedonian family with autosomal dominant spondylocostal dysostosis, originally described 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="#10" 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> performed whole-exome sequencing and identified a heterozygous mutation in the TBX6 gene (<a href="/entry/602427#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/?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><p><a href="#15" 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 23 individuals with congenital scoliosis in discovery and replication samples of Han Chinese individuals who carried a null allele of TBX6 (e.g., <a href="/entry/602427#0002">602427.0002</a>) and a common 3-SNP haplotype as the second TBX6 allele (<a href="/entry/602427#0003">602427.0003</a>). The null alleles comprised 16p11.2 deletions affecting TBX6, a nonsense mutation, and frameshift mutations. From an independent series of 42 Han Chinese patients with a 16p11.2 deletion, <a href="#15" 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 6 persons with congenital scoliosis, 5 of whom (83%) had the phenotype explained by TBX6 compound inheritance (p = 0.004). In vitro functional assays suggested that the haplotype functions as a hypomorphic allele. <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 26 patients from the 3 cohorts (newly reported patients from cohorts 1 and 2, and all patients in cohort 3) reported by <a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a>, all but 3 had a 16p11.2 deletion on the first allele. All but 2 of these 26 patients had the TCA risk haplotype on the second allele. One Hispanic patient carried a c.853C-T variant, which was novel in European populations; the allele of the other patient, a Caucasian female, was given as 'NA.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30636772" 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="#7" 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="/entry/602427#0003">602427.0003</a>) in trans. Combining these data with those of a previously reported Japanese cohort (<a href="#11" class="mim-tip-reference" title="Takeda, K., Kou, I., Kawakami, N., Iida, A., Nakajima, M., Ogura, Y., Imagawa, E., Miyake, N., Matsumoto, N., Yasuhiko, Y., Sudo, H., Kotani, T., Nakamura, M., Matsumoto, M., Watanabe, K., Ikegawa, S., Japan Early Onset Scoliosis Research Group. <strong>Compound heterozygosity for null mutations and a common hypomorphic risk haplotype in TBX6 causes congenital scoliosis.</strong> Hum. Mutat. 38: 317-323, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28054739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28054739</a>] [<a href="https://doi.org/10.1002/humu.23168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28054739">Takeda et al., 2017</a>), <a href="#7" 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> found that about 9.2% of Japanese patients with CS have a mutation in the TBX6 gene. One of 4 patients with spondylocostal dysostosis had biallelic missense variants (c.356G-A, R119H; c.449G-A, R150H); this patient did not have the risk haplotype on either allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28054739+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><strong><em>Exclusion Studies</em></strong></p><p>
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In a 3-generation Macedonian family segregating autosomal dominant spondylocostal dysostosis, <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> analyzed the 4 genes known to cause recessive forms of SCDO (see <a href="/entry/277300">277300</a>) but found no mutations. <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'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a> generated a TBX6 gene-edited mouse model for compound inheritance, with loss-of-function and mild hypomorphic (mh) alleles. Gene expression in vitro was downregulated by the Tbx6(mh) allele mutant to approximately 65% of the wildtype gene, close to the 70% dosage level of the human TBX6 mild hypomorphic allele. As predicted and consistent with literature observation, no homozygotes for the loss-of-function variant were identified in liveborn animals, and expected mendelian ratios of particular genotypic combinations were distorted in liveborns, consistent with embryonic lethality in Tbx6-null animals. <a href="#5" class="mim-tip-reference" title="Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others. <strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong> Genet. Med. 21: 1548-1558, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30636772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30636772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30636772[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/s41436-018-0377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30636772">Liu et al. (2019)</a> phenotypically assessed mice with 5 specific Tbx6 genotypes: homozygous wildtype, heterozygous wildtype/null, heterozygous wildtype/mh, homozygous mh, and heterozygous null/mh. Consistently, only the null/mh mice exhibited vertebral malformations. Similar to human, all Tbx6 null/mh mice had vertebral malformations involving the lower part of the spine. Defects of vertebral column formation were present in most of the null/mh mice. The recapitulation of the type, extent, and distribution of vertebral malformations in the engineered compound inheritance model in mice further supported the compound inheritance and gene dosage model for TACS and implicated the biologic perturbations in vertebral column malformations in this type of congenital scoliosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30636772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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[<a href="https://doi.org/10.1002/ajmg.a.33471" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/s41436-018-0377-x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320350215" target="_blank">Full Text</a>]
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<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>
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[<a href="https://doi.org/10.1136/jmedgenet-2018-105920" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0002-9343(68)90193-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00415439" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddt012" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.25.12.831" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1406829" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 10/12/2020
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<div class="row collapse" id="mimCollapseContributors">
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Ada Hamosh - updated : 03/12/2019<br>Ada Hamosh - updated : 3/26/2015<br>Marla J. F. O'Neill - updated : 2/17/2014<br>Marla J. F. O'Neill - updated : 1/10/2011<br>Marla J. F. O'Neill - updated : 1/3/2011<br>Marla J. F. O'Neill - updated : 10/19/2009<br>George E. Tiller - updated : 10/19/2009<br>Marla J. F. O'Neill - updated : 8/4/2005
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Creation Date:
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Victor A. McKusick : 6/23/1986
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carol : 08/30/2024
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alopez : 07/15/2024<br>carol : 06/17/2022<br>carol : 06/09/2022<br>carol : 11/06/2020<br>carol : 10/12/2020<br>carol : 10/16/2019<br>carol : 06/25/2019<br>carol : 06/24/2019<br>alopez : 03/12/2019<br>carol : 02/26/2019<br>carol : 10/31/2016<br>joanna : 10/28/2016<br>carol : 10/27/2016<br>joanna : 10/27/2016<br>carol : 08/09/2016<br>carol : 09/22/2015<br>alopez : 3/26/2015<br>carol : 2/23/2015<br>carol : 2/23/2015<br>carol : 2/18/2014<br>mcolton : 2/17/2014<br>carol : 2/29/2012<br>carol : 1/10/2011<br>carol : 1/3/2011<br>carol : 12/20/2010<br>joanna : 2/26/2010<br>carol : 10/19/2009<br>carol : 10/19/2009<br>wwang : 8/5/2005<br>terry : 8/4/2005<br>mgross : 3/17/2004<br>carol : 2/27/2003<br>carol : 7/1/1999<br>mark : 2/26/1996<br>mark : 2/26/1996<br>terry : 2/20/1996<br>mimadm : 6/25/1994<br>pfoster : 3/25/1994<br>warfield : 2/14/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>supermim : 2/27/1990
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<strong>#</strong> 122600
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<h3>
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SPONDYLOCOSTAL DYSOSTOSIS 5; SCDO5
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<em>Alternative titles; symbols</em>
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SCOLIOSIS, CONGENITAL, WITH OR WITHOUT RIB ANOMALIES<br />
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TACS<br />
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SPONDYLOCOSTAL DYSPLASIA<br />
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SPONDYLOTHORACIC DYSOSTOSIS<br />
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COSTOVERTEBRAL SEGMENTATION ANOMALIES
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<strong>ORPHA:</strong> 1797;
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<strong>DO:</strong> 0112363;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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16p11.2
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<span class="mim-font">
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Spondylocostal dysostosis 5
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<span class="mim-font">
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122600
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Autosomal dominant; Autosomal recessive
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<span class="mim-font">
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3
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TBX6
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602427
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that spondylocostal dysostosis-5 (SCDO5) is caused by heterozygous or compound heterozygous mutation in the TBX6 gene (602427) on chromosome 16p11.</p><p>For a general phenotypic description and a discussion of genetic heterogeneity of spondylocostal dysostosis, see SCDO1 (277300).</p>
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<strong>Clinical Features</strong>
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<p>Rimoin et al. (1968) reported a family in which father and son and probably 2 preceding generations were short of stature (less than 5 feet), the shortening being mainly in the trunk, and had multiple rib and vertebral anomalies. The number of ribs was reduced to 11 and several ribs were fused posteriorly. Hemivertebra and vertebral fusion were noted at multiple levels in the cervical and thoracic spine. No neurologic manifestations were present. Langer (1967) reported another family with multiple affected generations. </p><p>Ruett and Degenhardt (1959) described a 4-generation family (Familie Mck.) in which 4 individuals had congenital scoliosis. Van der Sar (1952) found multiple hemivertebrae and rib anomalies in a mother and daughter. </p><p>Ayme and Preus (1986) did a cluster analysis on reported cases of spondylocostal dysostosis, spondylothoracic dysplasia, and Jarcho-Levin syndrome. They concluded that the dominant and mild recessive forms of spondylothoracic dysplasia, falling into their cluster 2, could not be distinguished. </p><p>The family with affected members in 3 generations reported by Temple et al. (1988) may have had the same condition as that reported by Rimoin et al. (1968) and others. Short stature was striking. The rib changes were only mild. </p><p>Lorenz and Rupprecht (1990) reported the cases of a father and daughter. Abnormality of the ribs was more severe in the infant daughter than usual in this form and was suggestive of the changes found in the autosomal recessive type. </p><p>Gucev et al. (2010) studied an indigenous 3-generation Macedonian family segregating autosomal dominant spondylocostal dysostosis. The 12-year-old proband and his father and paternal uncle had disproportionately short trunks and necks with a normal range of movement, and radiographs revealed mild scoliosis with a mixture of hemivertebrae and vertebral blocks. The ribs were relatively mildly affected, with nearly normal alignment and a possible point of fusion high on the left posteriorly in the proband and mild thoracic sulci and flaring of the lower rib cage in the father and uncle. There were no other significant organ abnormalities, no obvious dysmorphic features, and neurodevelopment was normal. The paternal grandfather was deceased but was reported to have had the same phenotype. </p><p>Wu et al. (2015) reported 23 Han Chinese individuals with a diagnosis of congenital scoliosis that was related to compound heterozygous mutation in the TBX6 gene. All 23 individuals had 1 or more hemivertebrae. The number of hemivertebrae was significantly higher in patients with TBX6-related congenital scoliosis that in those with congenital scoliosis without TBX6 mutation. Rib abnormalities were also reported in most patients. </p><p>Liu et al. (2019) studied cohorts of patients with congenital scoliosis (CS), 345 from China (cohort 1), 142 from Japan (cohort 2), and 10 from the United States (cohort 3). Clinically measurable endophenotypes were compared according to the TBX6 genotypes. Liu et al. (2019) developed a clinical diagnostic algorithm (TACScore) to assist in clinical recognition of TBX6-associated CS (TACS). Cohort 1 included 33 TACS patients, and these were significantly younger at onset (median age 2 years) than the remaining CS patients (median age 3 years), presented with 1 or more hemivertebrae/butterfly vertebrae, and exhibited vertebral malformations involving the lower part of the spine (T8-S5); observations were confirmed in Japanese and US cohorts. Simple rib anomalies were prevalent in the TACS patients (present in 25 of 33) whereas intraspinal anomalies were uncommon (present in only 1 patient). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9. </p><p>Otomo et al. (2019) described 9 Japanese patients with congenital scoliosis with involvement of cervical thoracic and lumbar vertebral areas. Vertebral anomalies (blocked vertebrae, hemivertebrae, and butterfly vertebrae) were seen in all patients, with 3 patients also having rib anomalies. A Japanese patient with SCOD had multiple defects along the spine and multiple posterior fusions of the ribs. </p>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</h4>
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<p>The inheritance pattern of spondylocostal dysostosis-5 can be autosomal dominant (Sparrow et al., 2013) or autosomal recessive (Wu et al., 2015). </p><p>Liu et al. (2019) pointed out that SCDO5 does not follow conventional rare variant mendelian inheritance expectations, likely reflecting the embryonic lethality of TBX6 homozygous null alleles. Instead, SCDO5 is caused by biallelic variants at a locus, consistent with autosomal recessive trait manifestation, but with the presence of a single rare loss-of-function variant in trans with one common hypomorphic allele; a gene dosage that is less than haploinsufficiency but not 0, as with homozygous null alleles. Liu et al. (2019) suggested that this genetic model (compound inheritance and TACS) may provide an explanation for scenarios in which monoallelic variants and phenotypes are perceived to be following a dominant inheritance pattern, but for a disease trait with incomplete penetrance, or in which the disease pattern observed is pseudodominance, as found when the carrier state occurs at a high frequency in the population. Because the T-C-A haplotype is common worldwide (44% among Asians and 33% among Europeans, but less than 1% among Africans), the haplotype is likely to be parsed and filtered out by genomic analytical pipelines. </p>
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<h4>
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<strong>Cytogenetics</strong>
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<p>Polydysspondyly was described by Turpin et al. (1959) in association with a translocation involving group D and G chromosomes. De Grouchy et al. (1963) reported a similar condition in mother and daughter, both of whom carried a 14-15 translocation. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</h4>
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<p>In 3 affected and 2 unaffected members of a 3-generation Macedonian family with autosomal dominant spondylocostal dysostosis, originally described by Gucev et al. (2010), Sparrow et al. (2013) performed whole-exome sequencing and identified a heterozygous 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 23 individuals with congenital scoliosis in discovery and replication samples of Han Chinese individuals who carried a null allele of TBX6 (e.g., 602427.0002) and a common 3-SNP haplotype as the second TBX6 allele (602427.0003). The null alleles comprised 16p11.2 deletions affecting TBX6, a nonsense mutation, and frameshift mutations. From an independent series of 42 Han Chinese patients with a 16p11.2 deletion, Wu et al. (2015) identified 6 persons with congenital scoliosis, 5 of whom (83%) had the phenotype explained by TBX6 compound inheritance (p = 0.004). In vitro functional assays suggested that the haplotype functions as a hypomorphic allele. </p><p>Among 26 patients from the 3 cohorts (newly reported patients from cohorts 1 and 2, and all patients in cohort 3) reported by Liu et al. (2019), all but 3 had a 16p11.2 deletion on the first allele. All but 2 of these 26 patients had the TCA risk haplotype on the second allele. One Hispanic patient carried a c.853C-T variant, which was novel in European populations; the allele of the other patient, a Caucasian female, was given as 'NA.' </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. Combining these data with those of a previously reported Japanese cohort (Takeda et al., 2017), Otomo et al. (2019) found that about 9.2% of Japanese patients with CS have a mutation in the TBX6 gene. One of 4 patients with spondylocostal dysostosis had biallelic missense variants (c.356G-A, R119H; c.449G-A, R150H); this patient did not have the risk haplotype on either allele. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
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In a 3-generation Macedonian family segregating autosomal dominant spondylocostal dysostosis, Gucev et al. (2010) analyzed the 4 genes known to cause recessive forms of SCDO (see 277300) but found no mutations. </p>
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<strong>Nomenclature</strong>
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</span>
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</div>
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<span class="mim-text-font">
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<p>The terms dysostosis and dysplasia are used here interchangeably. Both words refer to abnormal development or formation.</p>
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</span>
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<div>
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<h4>
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Liu et al. (2019) generated a TBX6 gene-edited mouse model for compound inheritance, with loss-of-function and mild hypomorphic (mh) alleles. Gene expression in vitro was downregulated by the Tbx6(mh) allele mutant to approximately 65% of the wildtype gene, close to the 70% dosage level of the human TBX6 mild hypomorphic allele. As predicted and consistent with literature observation, no homozygotes for the loss-of-function variant were identified in liveborn animals, and expected mendelian ratios of particular genotypic combinations were distorted in liveborns, consistent with embryonic lethality in Tbx6-null animals. Liu et al. (2019) phenotypically assessed mice with 5 specific Tbx6 genotypes: homozygous wildtype, heterozygous wildtype/null, heterozygous wildtype/mh, homozygous mh, and heterozygous null/mh. Consistently, only the null/mh mice exhibited vertebral malformations. Similar to human, all Tbx6 null/mh mice had vertebral malformations involving the lower part of the spine. Defects of vertebral column formation were present in most of the null/mh mice. The recapitulation of the type, extent, and distribution of vertebral malformations in the engineered compound inheritance model in mice further supported the compound inheritance and gene dosage model for TACS and implicated the biologic perturbations in vertebral column malformations in this type of congenital scoliosis. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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</div>
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<ol>
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<p class="mim-text-font">
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Ayme, S., Preus, M.
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<strong>Spondylocostal/spondylothoracic dysostosis: the clinical basis for prognosticating and genetic counseling.</strong>
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Am. J. Med. Genet. 24: 599-606, 1986.
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[PubMed: 3740094]
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[Full Text: https://doi.org/10.1002/ajmg.1320240403]
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</li>
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<li>
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<p class="mim-text-font">
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de Grouchy, J., Mlynarski, J. C., Maroteaux, P., Lamy, M., Deshaies, G., Benichou, C., Salmon, C.
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<strong>Syndrome polydysspondylique par translocation 14-15 et dyschondrosteose chez un meme sujet. Segregation familiale.</strong>
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C. R. Hebd. Seances Acad. Sci. 256: 1614-1616, 1963.
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[PubMed: 13950852]
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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>
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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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Langer, L. O., Jr.
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<strong>Personal Communication.</strong>
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Minneapolis, Minn. 1967.
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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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Liu, J., Wu, N., Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Yang, N., Takeda, K., Chen, W., Li, W., Du, R., Liu, S., Zhou, Y., Zhang, L., Liu, Z., and 55 others.
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<strong>TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.</strong>
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Genet. Med. 21: 1548-1558, 2019.
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[PubMed: 30636772]
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[Full Text: https://doi.org/10.1038/s41436-018-0377-x]
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</p>
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Ruett, A., Degenhardt, K.-H.
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<strong>Beitrag zur Aetiologie und Pathogenese von Wirbelsaeulenmissbildungen.</strong>
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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.
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<strong>Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.</strong>
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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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