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Entry
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- #119300 - VAN DER WOUDE SYNDROME 1; VWS1
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- OMIM
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<p>
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<span class="h4">#119300</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/119300"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#otherFeatures">Other Features</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#mapping">Mapping</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=VAN DER WOUDE SYNDROME" 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=967&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/NBK1407/" 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/7346" 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://medlineplus.gov/genetics/condition/van-der-woude-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=119300[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=888" 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/9d8131e6-3bc5-49e1-86aa-1d9e36703d48/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>
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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:0060239" 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/119300" 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://omia.org/OMIA000197/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<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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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 79261008<br />
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<strong>ICD10CM:</strong> Q38.0<br />
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<strong>ORPHA:</strong> 888<br />
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<strong>DO:</strong> 0060239<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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119300
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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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VAN DER WOUDE SYNDROME 1; VWS1
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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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VDWS<br />
|
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LIP-PIT SYNDROME; LPS; PIT<br />
|
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CLEFT LIP AND/OR PALATE WITH MUCOUS CYSTS OF LOWER LIP
|
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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">
|
|
<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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<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/1/1670?start=-3&limit=10&highlight=1670">
|
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1q32.2
|
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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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van der Woude syndrome 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/119300"> 119300 </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>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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IRF6
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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/607199"> 607199 </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 class="btn-group ">
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<a href="/clinicalSynopsis/119300" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</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">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/119300" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/119300" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </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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- 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 />
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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> HEAD & NECK </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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<div>
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<span class="h5 mim-font">
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<em> Mouth </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Lower lip pits <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861544</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000196</a>]</span><br /> -
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Cleft lip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80281008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80281008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008924</a>, <a href="https://bioportal.bioontology.org/search?q=C4321245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4321245</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000204" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000204</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span><br /> -
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Cleft palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63567004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63567004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87979003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87979003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837218</a>, <a href="https://bioportal.bioontology.org/search?q=C2981150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2981150</a>, <a href="https://bioportal.bioontology.org/search?q=C2240378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240378</a>, <a href="https://bioportal.bioontology.org/search?q=C0008925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span><br /> -
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Cleft uvula <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18910001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18910001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266122&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266122</a>, <a href="https://bioportal.bioontology.org/search?q=C4551488&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551488</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000193" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000193</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000193" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000193</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3c22579bdef4e88303964de87353ca6f" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Uvula,Cleft-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3c22579bdef4e88303964de87353ca6f" 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 />
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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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<span class="h5 mim-font">
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<em> Teeth </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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- Hypodontia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64969001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64969001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020608</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</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> 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 interferon regulatory factor 6 gene (IRF6, <a href="/entry/607199#0001">607199.0001</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>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because van der Woude syndrome-1 (VWS1) is caused by heterozygous mutation in the gene encoding interferon regulatory factor-6 (IRF6; <a href="/entry/607199">607199</a>) on chromosome 1q32.</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, and cleft lip and/or cleft palate (CL/P, CP). It is the most common cleft syndrome.</p><p><strong><em>Genetic Heterogeneity of van der Woude Syndrome</em></strong></p><p>
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Also see VWS2 (<a href="/entry/606713">606713</a>), caused by mutation in the GRHL3 gene (<a href="/entry/608317">608317</a>) on chromosome 1p36.</p>
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</span>
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<div>
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<br />
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<div>
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</h4>
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</div>
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<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>In 3 generations of a family, <a href="#20" class="mim-tip-reference" title="Levy, J. <strong>Zwillinge in einer Familie mit Unterlippenmissbildung.</strong> Acta Genet. Statist. Med. 12: 33-40, 1962.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14464774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14464774</a>]" pmid="14464774">Levy (1962)</a> found malformations of the lower lip consisting of symmetrical lumps. Two sibs had cleft palate in addition to the lip anomaly. The literature on this syndrome was analyzed by <a href="#37" class="mim-tip-reference" title="van der Woude, A. <strong>Fistula labii inferioris congenita and its association with cleft lip and palate.</strong> Am. J. Hum. Genet. 6: 244-256, 1954.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13158329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13158329</a>]" pmid="13158329">van der Woude (1954)</a>, who found confirmation for the autosomal dominant mode of inheritance. It is possible that in some affected families, because of the variable expressivity of the gene, the syndrome is expressed only as pits. <a href="#1" class="mim-tip-reference" title="Baker, B. R. <strong>A family with bilateral congenital pits of the inferior lip.</strong> Oral Surg. 18: 494-497, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14198088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14198088</a>] [<a href="https://doi.org/10.1016/0030-4220(64)90398-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14198088">Baker (1964)</a> reported such a pedigree with affected members in 3 generations showing pits as the only malformation. On the other hand, only harelip and/or cleft palate without pits could segregate in families as a dominant trait. <a href="#36" class="mim-tip-reference" title="Test, A. R., Falls, H. F. <strong>Dominant inheritance of cleft lip and palate in five generations.</strong> J. Oral Surg. 5: 292-297, 1947.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18897035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18897035</a>]" pmid="18897035">Test and Falls (1947)</a> described the condition transmitted through 5 generations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14464774+14198088+18897035+13158329" 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 rule that cleft palate alone and cleft lip with or without cleft palate behave differently does not hold in this disorder, in which either type of cleft alone or the 2 in combination may occur. <a href="#16" class="mim-tip-reference" title="Janku, P., Robinow, M., Kelly, T., Bralley, R., Baynes, A., Edgerton, M. T. <strong>The van der Woude syndrome in a large kindred: variability, penetrance, genetic risks.</strong> Am. J. Med. Genet. 5: 117-123, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7395906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7395906</a>] [<a href="https://doi.org/10.1002/ajmg.1320050203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7395906">Janku et al. (1980)</a> traced the van der Woude syndrome through 7 generations. Lip pits, the most common manifestation, were present in 88% of the affected and were the only manifestation in 64%. Clefts of lip and palate occurred in 21%. Penetrance was 96.7%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7395906" 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="#27" class="mim-tip-reference" title="Ranta, R., Rintala, A. E. <strong>Correlations between microforms of the van der Woude syndrome and cleft palate.</strong> Cleft Palate J. 20: 158-162, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6573981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6573981</a>]" pmid="6573981">Ranta and Rintala (1983)</a> analyzed the 'microforms' of the van der Woude syndrome in cases of cleft palate. Conical elevations (CE) on the lower lip at the site of sinuses were present in 39.3% of cleft palate cases, 0.8% of cleft lip with or without cleft palate cases, and 0.7% of noncleft cases. In CP cases with CE, the familial occurrence of clefts was statistically higher (30%) than in CP cases without CE. The corresponding figures for hypodontia were 40.7% and 24.7%, respectively. See review by <a href="#29" class="mim-tip-reference" title="Schinzel, A., Klausler, M. <strong>The van der Woude syndrome (dominantly inherited lip pits and clefts).</strong> J. Med. Genet. 23: 291-294, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3746828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3746828</a>] [<a href="https://doi.org/10.1136/jmg.23.4.291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3746828">Schinzel and Klausler (1986)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3746828+6573981" 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="Burdick, A. B., Ma, L. A., Zhuohua, D., Ning, G. <strong>van der Woude syndrome in two families in China.</strong> J. Craniofac. Genet. Dev. Biol. 7: 413-418, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3429616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3429616</a>]" pmid="3429616">Burdick et al. (1987)</a> reported 2 unrelated families from the area of Beijing, China. Ankyloglossia was found in the proband in each family. <a href="#35" class="mim-tip-reference" title="Soricelli, D. A., Bell, L., Alexander, W. A. <strong>Congenital fistulas of the lower lip: a family case report.</strong> Oral Surg. 21: 511-516, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5218157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5218157</a>] [<a href="https://doi.org/10.1016/0030-4220(66)90410-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5218157">Soricelli et al. (1966)</a> also described this association. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3429616+5218157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Kocer, U., Aksoy, H. M., Tiftikcioglu, Y. O., Cologlu, H., Karaaslan, O. <strong>Report of two cases with van der Woude syndrome: a child and her mother.</strong> Genet. Counsel. 12: 341-346, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11837602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11837602</a>]" pmid="11837602">Kocer et al. (2001)</a> described a child with symmetrical lower lip pits and cleft palate whose mother had only a single lower lip pit in the right paramedian region. (The possibility of mosaicism in the mother might be raised. VAM) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11837602" 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="Birnbaum, S., Reutter, H., Lauster, C., Scheer, M., Schmidt, G., Saffar, M., Martini, M., Hemprich, A., Henschke, H., Kramer, F.-J., Mangold, E. <strong>Mutation screening in the IRF6-gene in patients with apparently nonsyndromic orofacial clefts and a positive family history suggestive of autosomal-dominant inheritance.</strong> Am. J. Med. Genet. 146A: 787-790, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18247422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18247422</a>] [<a href="https://doi.org/10.1002/ajmg.a.32219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18247422">Birnbaum et al. (2008)</a> analyzed the IRF6 gene in 63 families with what was believed to be isolated CL/P or CP and identified a deletion/insertion and duplication in 2 families, respectively. Despite 'credible denials' of a history of lip pits in family members, upon reinterviewing and retrieval of preoperative photographs, the presence of lip pits in both families confirmed the diagnosis of VWS. <a href="#3" class="mim-tip-reference" title="Birnbaum, S., Reutter, H., Lauster, C., Scheer, M., Schmidt, G., Saffar, M., Martini, M., Hemprich, A., Henschke, H., Kramer, F.-J., Mangold, E. <strong>Mutation screening in the IRF6-gene in patients with apparently nonsyndromic orofacial clefts and a positive family history suggestive of autosomal-dominant inheritance.</strong> Am. J. Med. Genet. 146A: 787-790, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18247422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18247422</a>] [<a href="https://doi.org/10.1002/ajmg.a.32219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18247422">Birnbaum et al. (2008)</a> noted that this is important for genetic counseling, because the recurrence risk of VWS is higher than the recurrence risk for nonsyndromic clefts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18247422" 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="#26" class="mim-tip-reference" title="Nopoulos, P., Richman, L., Andreasen, N. C., Murray, J. C., Schutte, B. <strong>Abnormal brain structure in adults with Van der Woude syndrome.</strong> Clin. Genet. 71: 511-517, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17539900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17539900</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00799.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17539900">Nopoulos et al. (2007)</a> reported brain MRI results in 7 adult men and 7 adult women with VWS. Seven of the affected patients belonged to a single large kindred; the remaining patients each came from a different family. Individuals with VWS had markedly larger gray matter volumes of the anterior cerebrum compared to controls, and there was a negative correlation between anterior gray matter volume and IQ, indicating that the changes had functional significance. Men with VWS also had decreased volumes of the posterior cerebrum. <a href="#26" class="mim-tip-reference" title="Nopoulos, P., Richman, L., Andreasen, N. C., Murray, J. C., Schutte, B. <strong>Abnormal brain structure in adults with Van der Woude syndrome.</strong> Clin. Genet. 71: 511-517, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17539900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17539900</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00799.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17539900">Nopoulos et al. (2007)</a> concluded that brain structure is altered in individuals with VWS, similar to that observed in patients with isolated cleft lip/palate (see <a href="/entry/119530">119530</a> and <a href="#25" class="mim-tip-reference" title="Nopoulos, P., Berg, S., Canady, J., Richman, L., Van Demark, D., Andreasen, N. C. <strong>Structural brain abnormalities in adult males with clefts of the lip and/or palate.</strong> Genet. Med. 4: 1-9, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11839951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11839951</a>] [<a href="https://doi.org/10.1097/00125817-200201000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11839951">Nopoulos et al., 2002</a>), suggesting that both disorders reflect abnormal brain development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17539900+11839951" 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="#4" class="mim-tip-reference" title="Bocian, M., Walker, A. P. <strong>Lip pits and deletion 1q32-q41.</strong> Am. J. Med. Genet. 26: 437-443, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3812594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3812594</a>] [<a href="https://doi.org/10.1002/ajmg.1320260223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3812594">Bocian and Walker (1987)</a> described a patient with an interstitial deletion of chromosome 1q, del(1q32-q41). Among other anomalies, the patient had congenital lower lip pits similar to those found in association with the van der Woude syndrome and with the popliteal pterygium syndrome. <a href="#4" class="mim-tip-reference" title="Bocian, M., Walker, A. P. <strong>Lip pits and deletion 1q32-q41.</strong> Am. J. Med. Genet. 26: 437-443, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3812594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3812594</a>] [<a href="https://doi.org/10.1002/ajmg.1320260223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3812594">Bocian and Walker (1987)</a> suggested that the van der Woude syndrome may be due to a submicroscopic deletion of chromosome 1q in the area stated. A tentative assignment of the locus, symbolized PIT, to 1q32-q41 was made on the basis of this report. <a href="#28" class="mim-tip-reference" title="Sander, A., Schmelzle, R., Murray, J. <strong>Evidence for a microdeletion in 1q32-41 involving the gene responsible for van der Woude syndrome.</strong> Hum. Molec. Genet. 3: 575-578, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069301</a>] [<a href="https://doi.org/10.1093/hmg/3.4.575" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069301">Sander et al. (1994)</a> reported a microdeletion involving 1q32-q41 in a family with VWS. They found allelic loss of the stable and highly polymorphic microsatellite D1S205. They estimated that the upper bound of the size of the deletion was 4 Mb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8069301+3812594" 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="#31" class="mim-tip-reference" title="Schutte, B. C., Basart, A. M., Watanabe, Y., Laffin, J. J. S., Coppage, K., Bjork, B. C., Daack-Hirsch, S., Patil, S., Dixon, M. J., Murray, J. C. <strong>Microdeletions at chromosome bands 1q32-q41 as a cause of van der Woude syndrome.</strong> Am. J. Med. Genet. 84: 145-150, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323740</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19990521)84:2<145::aid-ajmg11>3.0.co;2-l" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10323740">Schutte et al. (1999)</a> screened a panel of 37 VWS families for loss of transmission of an allele using a highly polymorphic marker (D1S3753) from the VWS critical region. Allele loss, indicating the presence of a deletion, was identified in 1 family. In this family, the phenotype in 3 generations of affected individuals was confined to the cardinal signs of VWS, in contrast to previously reported deletions in which developmental delay and other anomalies accompanied features of VWS (<a href="#4" class="mim-tip-reference" title="Bocian, M., Walker, A. P. <strong>Lip pits and deletion 1q32-q41.</strong> Am. J. Med. Genet. 26: 437-443, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3812594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3812594</a>] [<a href="https://doi.org/10.1002/ajmg.1320260223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3812594">Bocian and Walker, 1987</a>; <a href="#28" class="mim-tip-reference" title="Sander, A., Schmelzle, R., Murray, J. <strong>Evidence for a microdeletion in 1q32-41 involving the gene responsible for van der Woude syndrome.</strong> Hum. Molec. Genet. 3: 575-578, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069301</a>] [<a href="https://doi.org/10.1093/hmg/3.4.575" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069301">Sander et al., 1994</a>). <a href="#14" class="mim-tip-reference" title="Houdayer, C., Soupre, V., Karcenty, B., Vazquez, M.-P., Odent, S., Lacombe, D., Le Bouc, Y., Munnich, A., Bahuau, M. <strong>1q32-q41 microdeletion with reference to van der Woude syndrome and allied clefting entities. (Letter)</strong> Am. J. Med. Genet. 91: 161-163, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748420</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000313)91:2<161::aid-ajmg18>3.0.co;2-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10748420">Houdayer et al. (2000)</a> performed a microsatellite-based screening test for 1q32-q41 haploinsufficiency on 14 family triads with VWS and identified no additional microdeletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8069301+10323740+3812594+10748420" 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="#39" class="mim-tip-reference" title="Wienker, T. F., Hudek, G., Bissbort, S., Mayerova, A., Mauff, G., Bender, K. <strong>Linkage studies in a pedigree with van der Woude syndrome.</strong> J. Med. Genet. 24: 160-161, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3572998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3572998</a>] [<a href="https://doi.org/10.1136/jmg.24.3.160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3572998">Wienker et al. (1987)</a> excluded linkage of VDWS with a considerable number of marker loci in studies of a kindred segregating for the disorder through 5 generations. Only linkage with Duffy blood group (<a href="/entry/110700">110700</a>) showed a uniformly positive lod score (lod = 1.31 at theta = 0.0). <a href="#22" class="mim-tip-reference" title="Murray, J. C., Nishimura, D., Ardinger, H., Buetow, K., Spence, A., Falk, R., Falk, P., Sparkes, R., Gardner, R. J. M., Glinski, L., Pauli, R., Nakamura, Y., Green, P., Yamada, Y. <strong>Linkage of van der Woude syndrome to markers on chromosome 1q and exclusion of laminin B2 as a candidate gene. (Abstract)</strong> Am. J. Hum. Genet. 43: A153 only, 1988."None>Murray et al. (1988)</a> found linkage of LPS to the renin gene (REN; <a href="/entry/179820">179820</a>); lod = 4.62 at theta = 0.04. Studies by <a href="#24" class="mim-tip-reference" title="Nishimura, D. Y., Buetow, K. H., Spence, M. A., Gardner, R. J. M., Pauli, R., Nakamura, Y., Green, P., Schinzel, A., Murray, J. C. <strong>Linkage of van der Woude syndrome (LPS) to renin on 1q. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1053 only, 1989."None>Nishimura et al. (1989)</a> raised the maximum lod score to 8.62 at theta = 0.02 for linkage of LPS and REN. <a href="#22" class="mim-tip-reference" title="Murray, J. C., Nishimura, D., Ardinger, H., Buetow, K., Spence, A., Falk, R., Falk, P., Sparkes, R., Gardner, R. J. M., Glinski, L., Pauli, R., Nakamura, Y., Green, P., Yamada, Y. <strong>Linkage of van der Woude syndrome to markers on chromosome 1q and exclusion of laminin B2 as a candidate gene. (Abstract)</strong> Am. J. Hum. Genet. 43: A153 only, 1988."None>Murray et al. (1988)</a> and <a href="#24" class="mim-tip-reference" title="Nishimura, D. Y., Buetow, K. H., Spence, M. A., Gardner, R. J. M., Pauli, R., Nakamura, Y., Green, P., Schinzel, A., Murray, J. C. <strong>Linkage of van der Woude syndrome (LPS) to renin on 1q. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1053 only, 1989."None>Nishimura et al. (1989)</a> also adopted a candidate gene approach and investigated whether the laminin B2 (<a href="/entry/150290">150290</a>) gene might be the site of the mutation in VDWS. The finding of several recombinants ruled out this possibility. <a href="#24" class="mim-tip-reference" title="Nishimura, D. Y., Buetow, K. H., Spence, M. A., Gardner, R. J. M., Pauli, R., Nakamura, Y., Green, P., Schinzel, A., Murray, J. C. <strong>Linkage of van der Woude syndrome (LPS) to renin on 1q. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1053 only, 1989."None>Nishimura et al. (1989)</a> used the same approach to investigate decay accelerating factor (<a href="/entry/125240">125240</a>) as the site of the mutation and found no recombinants (lod = 2.22). <a href="#23" class="mim-tip-reference" title="Murray, J. C., Nishimura, D. Y., Buetow, K. H., Ardinger, H. H., Spence, M. A., Sparkes, R. S., Falk, R. E., Falk, P. M., Gardner, R. J. M., Harkness, E. M., Glinski, L. P., Pauli, R. M., Nakamura, Y., Green, P. P., Schinzel, A. <strong>Linkage of an autosomal dominant clefting syndrome (van der Woude) to loci on chromosome 1q.</strong> Am. J. Hum. Genet. 46: 486-491, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309700</a>]" pmid="2309700">Murray et al. (1990)</a> reported a multipoint linkage analysis that indicated flanking of the VDWS locus by REN and D1S65 at a lod score of 10.83. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3572998+2309700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Schutte, B. C., Sander, A., Malik, M., Murray, J. C. <strong>Refinement of the van der Woude gene location and construction of a 3.5-Mb YAC contig and STS map spanning the critical region in 1q32-q41.</strong> Genomics 36: 507-514, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8884274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8884274</a>] [<a href="https://doi.org/10.1006/geno.1996.0496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8884274">Schutte et al. (1996)</a> constructed a 3.5-Mb YAC contig and sequence tagged site (STS) map extending from D1S245 to D1S414 in the region containing the VWS locus. They also carried out deletion mapping on a somatic cell hybrid derived from a patient with VWS due to a microdeletion. Analysis of this hybrid and genetic analysis in an additional family narrowed the VWS critical region to a 1.6-cM region flanked by D1S491 and D1S205. The authors noted that the STS markers that flank this critical region and the proximal and distal ends of the microdeletion are present in a single 850-kb YAC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8884274" 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="Houdayer, C., Soupre, V., Rosenberg-Bourgin, M., Martinez, H., Tredano, M., Feldmann, D., Feingold, J., Aymard, P., Munnich, A., Le Bouc, Y., Vazquez, M. P., Bahuau, M. <strong>Linkage analysis of 5 novel van der Woude syndrome kindreds to 1q32-q41 markers further supports locus homogeneity of the disease trait.</strong> Ann. Genet. 42: 69-74, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10434119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10434119</a>]" pmid="10434119">Houdayer et al. (1999)</a> studied the linkage of 6 microsatellite markers in the 1q32-q41 region to the disease phenotype in 5 Caucasian VWS kindreds. A maximum cumulative lod score of 3.27 at a recombination fraction of 0.00 was obtained with marker D1S245. The inner 4 markers were found to be tightly linked to one another without recombination. The authors concluded that the results favored locus homogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10434119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In studies of 4 multiplex Caucasian VWS families that had been recruited at 3 different locations in the U.S., <a href="#2" class="mim-tip-reference" title="Beiraghi, S., Miller-Chisholm, A., Kimberling, W. J., Sun, C., Wang, Y.-F., Russell, L. J., Khoshnevisan, M. H., Storm, A. L., Long, R. E., Jr., Witt, P. D., Mazaheri, M., Diehl, S. R. <strong>Confirmation of linkage of van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation.</strong> J. Craniofac. Genet. Dev. Biol. 19: 128-134, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10589394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10589394</a>]" pmid="10589394">Beiraghi et al. (1999)</a> found positive lod scores without any recombination in the candidate region of 1q. The largest 2-point lod score was 5.87. They used an assay method for short tandem repeat (STR) markers that provided highly accurate size estimation of marker allele fragment sizes, enabling them to determine the specific alleles segregating with the VWS gene in each of the 4 families. They observed a striking pattern of STR allele sharing at several closely linked loci among the 4 VWS families. These results suggested the possibility of a unique (i.e., single) origin for the mutation responsible for many or most cases of VWS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10589394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Lees, M. M., Winter, R. M., Malcolm, S., Saal, H. M., Chitty, L. <strong>Popliteal pterygium syndrome: a clinical study of three families and report of linkage to the van der Woude syndrome locus on 1q32.</strong> J. Med. Genet. 36: 888-892, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10593995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10593995</a>]" pmid="10593995">Lees et al. (1999)</a> reported clinical features and linkage analysis in 3 families with popliteal pterygium syndrome. Linkage analysis showed a multipoint lod score of 2.7 with no evidence of recombination using the markers D1S205, D1S491, and D1S3753 in the critical region for VWS on chromosome 1q32, supporting the hypothesis that these 2 conditions are allelic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10593995" 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 cardinal features of van der Woude syndrome are lip pits and cleft lip with or without cleft palate or cleft palate (alone) (<a href="/entry/119540">119540</a>). Since none of these traits is present in all mutation carriers, some individuals or familial VWS cases, especially those lacking lip pits, are indiscernible from nonsyndromic CL/P (<a href="/entry/119530">119530</a>), raising the question of whether allelic variation at the VWS locus could underlie nonsyndromic CL/P. <a href="#13" class="mim-tip-reference" title="Houdayer, C., Bonaiti-Pellie, C., Erguy, C., Soupre, V., Dondon, M.-G., Burglen, L., Cougoureux, E., Couderc, R., Vazquez, M.-P., Bahuau, M. <strong>Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).</strong> Am. J. Med. Genet. 104: 86-92, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746036</a>] [<a href="https://doi.org/10.1002/1096-8628(20011115)104:1<86::aid-ajmg10053>3.0.co;2-e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11746036">Houdayer et al. (2001)</a> addressed this question using parametric linkage (lod score) analysis in 21 multiplex nonsyndromic CL/P families based on a tightly linked microsatellite marker (D1S3753) and nonparametric analysis using the transmission/disequilibrium test in 106 nonsyndromic CL/P triads (2 parents and an offspring) and 3 selecting markers on chromosome 1. No evidence for linkage of nonsyndromic CL/P to VWS was found on the 21 families using the lod score approach. In contrast, the transmission/disequilibrium test yielded a significant P value of 0.04 for D1S205, supporting involvement of VWS in nonsyndromic CL/P in a complex, modifying/polygenic manner rather than as a monogenic/major disease locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Wong, F. K., Koillinen, H., Rautio, J., Teh, B. T., Ranta, R., Karsten, A., Larson, O., Linder-Aronson, S., Huggare, J., Larsson, C., Kere, J. <strong>Genetic heterogeneity and exclusion of a modifying locus at 17p11.2-p11.1 in Finnish families with van der Woude syndrome.</strong> J. Med. Genet. 38: 198-202, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11303516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11303516</a>] [<a href="https://doi.org/10.1136/jmg.38.3.198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11303516">Wong et al. (2001)</a> performed linkage analysis in 5 Finnish families with VWS. Three of these families were linked to the 1q32-q41 region. A recombination in an unaffected individual reduced the critical region to a 200-kb interval bounded by the markers at D1S491 and D1S3753. The authors expressed caution about the use of apparently unaffected individuals in a condition with low expressivity. Linkage disequilibrium suggested that the critical region was 130 kb bounded by the markers at D1S491 and D1S2136. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11303516" 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>Modifier Loci</em></strong></p><p>
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The expression of VWS, which has incomplete penetrance, is highly variable. Both the occurrence of cleft lip/palate and cleft palate within the same kindred and a recurrence risk of less than 40% for cleft palate among descendants with VWS suggested that the development of clefts in this syndrome is influenced by modifying genes at other loci. To test this hypothesis, <a href="#33" class="mim-tip-reference" title="Sertie, A. L., Sousa, A. V., Steman, S., Pavanello, R. C., Passos-Bueno, M. R. <strong>Linkage analysis in a large Brazilian family with van der Woude syndrome suggests the existence of a susceptibility locus for cleft palate at 17p11.2-11.1.</strong> Am. J. Hum. Genet. 65: 433-440, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417286</a>] [<a href="https://doi.org/10.1086/302491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417286">Sertie et al. (1999)</a> conducted linkage analysis in a large Brazilian kindred with VWS, considering as affected the individuals with CP, regardless of whether it was associated with other clinical signs of VWS. The results suggested that a gene at 17p11.2-p11.1 (<a href="/entry/604547">604547</a>), together with the VWS gene at 1q32, enhances the probability of CP in an individual carrying the 2 at-risk genes. <a href="#33" class="mim-tip-reference" title="Sertie, A. L., Sousa, A. V., Steman, S., Pavanello, R. C., Passos-Bueno, M. R. <strong>Linkage analysis in a large Brazilian family with van der Woude syndrome suggests the existence of a susceptibility locus for cleft palate at 17p11.2-11.1.</strong> Am. J. Hum. Genet. 65: 433-440, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417286</a>] [<a href="https://doi.org/10.1086/302491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417286">Sertie et al. (1999)</a> stated that if this hypothesis is confirmed in other VWS pedigrees, it will represent one of the first examples of a gene, mapped through linkage analysis, that modifies the expression of a major gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417286" 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 transmission pattern of VWS1 in the families reported by <a href="#18" class="mim-tip-reference" title="Kondo, S., Schutte, B. C., Richardson, R. J., Bjork, B. C., Knight, A. S., Watanabe, Y., Howard, E., Ferreira de Lima, R. L. L., Daack-Hirsch, S., Sander, A., McDonald-McGinn, D. M., Zackai, E. H., and 14 others. <strong>Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. (Letter)</strong> Nature Genet. 32: 285-289, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12219090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12219090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12219090[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/ng985" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12219090">Kondo et al. (2002)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12219090" 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 efforts to clone the VWS gene, <a href="#38" class="mim-tip-reference" title="Watanabe, Y., Murray, J. C., Bjork, B. C., Bird, C. P., Chiang, P.-W., Gregory, S. G., Kurnit, D. M., Schutte, B. C. <strong>Matroshka and ectopic polymorphisms: two new classes of DNA sequence variation identified at the van der Woude syndrome locus on 1q32-q41.</strong> Hum. Mutat. 18: 422-434, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668635</a>] [<a href="https://doi.org/10.1002/humu.1213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668635">Watanabe et al. (2001)</a> analyzed 900 kb of genomic sequence from the critical region of 1q32-q41. They found a polymorphism within a polymorphism that is a deletion/insertion (del/ins) polymorphism with a TTCC short tandem repeat (STR) embedded within it. They suggested that this be called a 'matroshka' polymorphism, after the Russian doll that has additional dolls nested inside. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668635" 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="#18" class="mim-tip-reference" title="Kondo, S., Schutte, B. C., Richardson, R. J., Bjork, B. C., Knight, A. S., Watanabe, Y., Howard, E., Ferreira de Lima, R. L. L., Daack-Hirsch, S., Sander, A., McDonald-McGinn, D. M., Zackai, E. H., and 14 others. <strong>Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. (Letter)</strong> Nature Genet. 32: 285-289, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12219090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12219090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12219090[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/ng985" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12219090">Kondo et al. (2002)</a> performed direct sequence analysis of genes and presumptive transcripts in the 350-kb VWS critical region identified by linkage analysis and identified mutations in the IRF6 gene, encoding interferon regulatory factor-6. They found a nonsense mutation in exon 4 of the IRF6 gene (<a href="/entry/607199#0001">607199.0001</a>) in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, they identified mutations in 45 additional unrelated families with VWS and distinct mutations in 13 families with popliteal pterygium syndrome (<a href="/entry/119500">119500</a>). In a family whose affected members showed cleft lip with or without cleft palate and isolated cleft palate, <a href="#18" class="mim-tip-reference" title="Kondo, S., Schutte, B. C., Richardson, R. J., Bjork, B. C., Knight, A. S., Watanabe, Y., Howard, E., Ferreira de Lima, R. L. L., Daack-Hirsch, S., Sander, A., McDonald-McGinn, D. M., Zackai, E. H., and 14 others. <strong>Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. (Letter)</strong> Nature Genet. 32: 285-289, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12219090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12219090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12219090[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/ng985" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12219090">Kondo et al. (2002)</a> found that all affected members regardless of phenotype shared the 18-bp deletion (<a href="/entry/607199#0002">607199.0002</a>) found in the proband. The authors hypothesized that marked phenotypic variation in their cohort strongly implicated the action of stochastic factors or modifier genes on IRF6 function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12219090" 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="#12" class="mim-tip-reference" title="Ghassibe, M., Revencu, N., Bayet, B., Gillerot, Y., Vanwijck, R., Verellen-Dumoulin, C., Vikkula, M. <strong>Six families with van der Woude and/or popliteal pterygium syndrome: all with a mutation in the IRF6 gene.</strong> J. Med. Genet. 41: e15, 2004. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14757865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14757865</a>] [<a href="https://doi.org/10.1136/jmg.2003.009274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14757865">Ghassibe et al. (2004)</a> screened the IRF6 gene in 6 families with VWS and identified 6 heterozygous missense mutations, respectively, all affecting either the DNA-binding or the protein-binding domain. In a 4-generation VWS family in which affected individuals carried an L22P mutation (<a href="/entry/607199#0014">607199.0014</a>), 2 of the patients displayed additional features: 1 had finger syndactyly, and the other had toe syndactyly and oral synechiae. <a href="#12" class="mim-tip-reference" title="Ghassibe, M., Revencu, N., Bayet, B., Gillerot, Y., Vanwijck, R., Verellen-Dumoulin, C., Vikkula, M. <strong>Six families with van der Woude and/or popliteal pterygium syndrome: all with a mutation in the IRF6 gene.</strong> J. Med. Genet. 41: e15, 2004. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14757865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14757865</a>] [<a href="https://doi.org/10.1136/jmg.2003.009274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14757865">Ghassibe et al. (2004)</a> stated that because syndactyly and synechiae are major signs for PPS, these 2 patients were considered to have PPS, whereas the 6 other affected family members were classified as VWS, thus demonstrating that a single mutation could be responsible for both syndromes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14757865" 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="#41" class="mim-tip-reference" title="Yeetong, P., Mahatumarat, C., Siriwan, P., Rojvachiranonda, N., Suphapeetiporn, K., Shotelersuk, V. <strong>Three novel mutations of the IRF6 gene with one associated with an unusual feature in van der Woude syndrome.</strong> Am. J. Med. Genet. 149A: 2489-2492, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19842205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19842205</a>] [<a href="https://doi.org/10.1002/ajmg.a.33048" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19842205">Yeetong et al. (2009)</a> reported 3 female patients with lower lip anomalies, all of whom had heterozygous mutations in the IRF6 gene. One patient was a 16-year-old girl with bilateral conical elevations without pits, joining at the midline of the lower lip, giving the appearance of a heart-shaped mass; she was heterozygous for a nonsense mutation (Q49X; <a href="/entry/607199#0017">607199.0017</a>). Her mother and other relatives were reported to have similar findings, but were unavailable for evaluation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19842205" 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="#21" class="mim-tip-reference" title="Malik, S., Kakar, N., Hasnain, S., Ahmad, J., Wilcox, E. R., Naz, S. <strong>Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan.</strong> Clin. Genet. 78: 247-256, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20184620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20184620</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01375.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20184620">Malik et al. (2010)</a> identified 16 Pakistani probands with VWS from more than 1,200 individuals with CL/P, for a frequency of approximately 1% in Pakistan. Analysis of IRF6 in the 16 VWS probands identified mutations in 12 of them (see, e.g., <a href="/entry/607199#0009">607199.0009</a> and <a href="/entry/607199#0018">607199.0018</a>), including 2 missense mutations that previously had been identified in patients with popliteal pterygium syndrome (PPS). While no clinical signs of PPS were identified or reported by these patients or their families, <a href="#21" class="mim-tip-reference" title="Malik, S., Kakar, N., Hasnain, S., Ahmad, J., Wilcox, E. R., Naz, S. <strong>Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan.</strong> Clin. Genet. 78: 247-256, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20184620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20184620</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01375.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20184620">Malik et al. (2010)</a> noted that subtler signs of PPS such as genital hypoplasia may have been present but were not evaluated in this study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20184620" 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>To test whether DNA variants in regulatory elements cause VWS, <a href="#11" class="mim-tip-reference" title="Fakhouri, W. D., Rahimov, F., Attanasio, C., Kouwenhoven, E. N., Ferreira De Lima, R. L., Felix, T. M., Nitschke, L., Huver, D., Barrons, J., Kousa, Y. A., Leslie, E., Pennacchio, L. A., Van Bokhoven, H., Visel, A., Zhou, H., Murray, J. C., Schutte, B. C. <strong>An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects.</strong> Hum. Molec. Genet. 23: 2711-2720, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24442519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24442519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24442519[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/10.1093/hmg/ddt664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24442519">Fakhouri et al. (2014)</a> sequenced 3 conserved elements near IRF6 in 70 VWS families who were negative for mutations with IRF6 exons and identified a duplication (350dupA) within a highly conserved sequence in the MCS9.7 enhancer element in a 3-generation Brazilian family. The duplication was present in 3 affected individuals as well as in 2 unaffected family members, but it was not found in 100 unaffected controls or in 1,092 genomes from 14 populations in the NHLBI Exome Sequencing Project database. Functional analysis demonstrated that the 350dupA mutation disrupted MCS9.7 enhancer activity in 2 different cell lines as well as in vivo in a transgenic mouse embryo assay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24442519" 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>Van der Woude Syndrome-Popliteal Pterygium Syndrome Spectrum</em></strong></p><p>
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In a patient with overlapping features of VWS and PPS (unilateral cleft lip and palate, ankyloblepharon, paramedian lip pits) as well as unilateral renal aplasia and coronal hypospadias, <a href="#9" class="mim-tip-reference" title="de Medeiros, F., Hansen, L., Mawlad, E., Eiberg, H., Asklund, C., Tommerup, N., Jakobsen, L. P. <strong>A novel mutation in IRF6 resulting in VWS-PPS spectrum disorder with renal aplasia.</strong> Am. J. Med. Genet. 146A: 1605-1608, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478600</a>] [<a href="https://doi.org/10.1002/ajmg.a.32257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18478600">de Medeiros et al. (2008)</a> identified a novel heterozygous mutation in the IRF6 gene (<a href="/entry/607199#0013">607199.0013</a>). The patient and his brother, who had hypospadias and nephrocalcinosis but no IRF6 mutation, were both conceived by in vitro fertilization. <a href="#9" class="mim-tip-reference" title="de Medeiros, F., Hansen, L., Mawlad, E., Eiberg, H., Asklund, C., Tommerup, N., Jakobsen, L. P. <strong>A novel mutation in IRF6 resulting in VWS-PPS spectrum disorder with renal aplasia.</strong> Am. J. Med. Genet. 146A: 1605-1608, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478600</a>] [<a href="https://doi.org/10.1002/ajmg.a.32257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18478600">De Medeiros et al. (2008)</a> suggested that the hypospadias and renal aplasia may have been due to the method of fertilization rather than the IRF6 mutation. They noted that a lethal PPS syndrome (<a href="/entry/263650">263650</a>) has renal aplasia as a feature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18478600" 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>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between van der Woude syndrome and mutation in the CFAP57 gene, see <a href="/entry/614259#0001">614259.0001</a>.</p>
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<a href="#Bowers1970" class="mim-tip-reference" title="Bowers, D. G. <strong>Congenital lower lip sinuses with cleft palate.</strong> Plast. Reconst. Surg. 45: 151-154, 1970.">Bowers (1970)</a>; <a href="#Burdick1985" class="mim-tip-reference" title="Burdick, A. B., Bixler, D., Puckett, C. L. <strong>Genetic analysis in families with van der Woude syndrome.</strong> J. Craniofac. Genet. Dev. Biol. 5: 181-208, 1985.">Burdick et al. (1985)</a>; <a href="#Cervenka1967" class="mim-tip-reference" title="Cervenka, J., Gorlin, R. J., Anderson, V. E. <strong>The syndrome of pits of the lower lip and cleft lip and/or palate: genetic considerations.</strong> Am. J. Hum. Genet. 19: 416-432, 1967.">Cervenka et al. (1967)</a>; <a href="#Eastman1978" class="mim-tip-reference" title="Eastman, J. R., Bixler, D., Escobar, V. <strong>Linkage studies in van der Woude syndrome.</strong> J. Med. Genet. 15: 217-281, 1978.">Eastman
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et al. (1978)</a>; <a href="#Schneider1973" class="mim-tip-reference" title="Schneider, E. L. <strong>Lip pits and congenital absence of second premolars: varied expression of the lip pits syndrome.</strong> J. Med. Genet. 10: 346-349, 1973.">Schneider (1973)</a>; <a href="#Shprintzen1980" class="mim-tip-reference" title="Shprintzen, R. J., Goldberg, R. B., Sidoti, E. J. <strong>The penetrance and variable expression of the van der Woude syndrome: implications for genetic counseling.</strong> Cleft Palate J. 17: 52-57, 1980.">Shprintzen et al. (1980)</a>
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Baker, B. R.
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<strong>A family with bilateral congenital pits of the inferior lip.</strong>
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Oral Surg. 18: 494-497, 1964.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14198088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14198088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14198088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Beiraghi, S., Miller-Chisholm, A., Kimberling, W. J., Sun, C., Wang, Y.-F., Russell, L. J., Khoshnevisan, M. H., Storm, A. L., Long, R. E., Jr., Witt, P. D., Mazaheri, M., Diehl, S. R.
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<strong>Confirmation of linkage of van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation.</strong>
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J. Craniofac. Genet. Dev. Biol. 19: 128-134, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10589394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10589394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10589394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Mutation screening in the IRF6-gene in patients with apparently nonsyndromic orofacial clefts and a positive family history suggestive of autosomal-dominant inheritance.</strong>
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Am. J. Med. Genet. 146A: 787-790, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18247422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18247422</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18247422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Am. J. Med. Genet. 26: 437-443, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3812594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3812594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3812594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Congenital lower lip sinuses with cleft palate.</strong>
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Plast. Reconst. Surg. 45: 151-154, 1970.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5411896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5411896</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5411896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Burdick1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burdick, A. B., Bixler, D., Puckett, C. L.
|
|
<strong>Genetic analysis in families with van der Woude syndrome.</strong>
|
|
J. Craniofac. Genet. Dev. Biol. 5: 181-208, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4019732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4019732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4019732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Burdick1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burdick, A. B., Ma, L. A., Zhuohua, D., Ning, G.
|
|
<strong>van der Woude syndrome in two families in China.</strong>
|
|
J. Craniofac. Genet. Dev. Biol. 7: 413-418, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3429616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3429616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3429616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cervenka1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cervenka, J., Gorlin, R. J., Anderson, V. E.
|
|
<strong>The syndrome of pits of the lower lip and cleft lip and/or palate: genetic considerations.</strong>
|
|
Am. J. Hum. Genet. 19: 416-432, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6026934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6026934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6026934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="de Medeiros2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Medeiros, F., Hansen, L., Mawlad, E., Eiberg, H., Asklund, C., Tommerup, N., Jakobsen, L. P.
|
|
<strong>A novel mutation in IRF6 resulting in VWS-PPS spectrum disorder with renal aplasia.</strong>
|
|
Am. J. Med. Genet. 146A: 1605-1608, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18478600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18478600</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18478600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.32257" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Eastman1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eastman, J. R., Bixler, D., Escobar, V.
|
|
<strong>Linkage studies in van der Woude syndrome.</strong>
|
|
J. Med. Genet. 15: 217-281, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/671486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">671486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=671486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.15.3.217" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Fakhouri2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fakhouri, W. D., Rahimov, F., Attanasio, C., Kouwenhoven, E. N., Ferreira De Lima, R. L., Felix, T. M., Nitschke, L., Huver, D., Barrons, J., Kousa, Y. A., Leslie, E., Pennacchio, L. A., Van Bokhoven, H., Visel, A., Zhou, H., Murray, J. C., Schutte, B. C.
|
|
<strong>An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects.</strong>
|
|
Hum. Molec. Genet. 23: 2711-2720, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24442519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24442519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24442519[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24442519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddt664" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Ghassibe2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ghassibe, M., Revencu, N., Bayet, B., Gillerot, Y., Vanwijck, R., Verellen-Dumoulin, C., Vikkula, M.
|
|
<strong>Six families with van der Woude and/or popliteal pterygium syndrome: all with a mutation in the IRF6 gene.</strong>
|
|
J. Med. Genet. 41: e15, 2004. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14757865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14757865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14757865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2003.009274" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Houdayer2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Houdayer, C., Bonaiti-Pellie, C., Erguy, C., Soupre, V., Dondon, M.-G., Burglen, L., Cougoureux, E., Couderc, R., Vazquez, M.-P., Bahuau, M.
|
|
<strong>Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).</strong>
|
|
Am. J. Med. Genet. 104: 86-92, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746036</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1096-8628(20011115)104:1<86::aid-ajmg10053>3.0.co;2-e" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Houdayer2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Houdayer, C., Soupre, V., Karcenty, B., Vazquez, M.-P., Odent, S., Lacombe, D., Le Bouc, Y., Munnich, A., Bahuau, M.
|
|
<strong>1q32-q41 microdeletion with reference to van der Woude syndrome and allied clefting entities. (Letter)</strong>
|
|
Am. J. Med. Genet. 91: 161-163, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10748420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8628(20000313)91:2<161::aid-ajmg18>3.0.co;2-q" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Houdayer1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Houdayer, C., Soupre, V., Rosenberg-Bourgin, M., Martinez, H., Tredano, M., Feldmann, D., Feingold, J., Aymard, P., Munnich, A., Le Bouc, Y., Vazquez, M. P., Bahuau, M.
|
|
<strong>Linkage analysis of 5 novel van der Woude syndrome kindreds to 1q32-q41 markers further supports locus homogeneity of the disease trait.</strong>
|
|
Ann. Genet. 42: 69-74, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10434119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10434119</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10434119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Janku1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janku, P., Robinow, M., Kelly, T., Bralley, R., Baynes, A., Edgerton, M. T.
|
|
<strong>The van der Woude syndrome in a large kindred: variability, penetrance, genetic risks.</strong>
|
|
Am. J. Med. Genet. 5: 117-123, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7395906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7395906</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7395906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320050203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Kocer2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kocer, U., Aksoy, H. M., Tiftikcioglu, Y. O., Cologlu, H., Karaaslan, O.
|
|
<strong>Report of two cases with van der Woude syndrome: a child and her mother.</strong>
|
|
Genet. Counsel. 12: 341-346, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11837602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11837602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11837602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kondo2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kondo, S., Schutte, B. C., Richardson, R. J., Bjork, B. C., Knight, A. S., Watanabe, Y., Howard, E., Ferreira de Lima, R. L. L., Daack-Hirsch, S., Sander, A., McDonald-McGinn, D. M., Zackai, E. H., and 14 others.
|
|
<strong>Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. (Letter)</strong>
|
|
Nature Genet. 32: 285-289, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12219090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12219090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12219090[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12219090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng985" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Lees1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lees, M. M., Winter, R. M., Malcolm, S., Saal, H. M., Chitty, L.
|
|
<strong>Popliteal pterygium syndrome: a clinical study of three families and report of linkage to the van der Woude syndrome locus on 1q32.</strong>
|
|
J. Med. Genet. 36: 888-892, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10593995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10593995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10593995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Levy1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Levy, J.
|
|
<strong>Zwillinge in einer Familie mit Unterlippenmissbildung.</strong>
|
|
Acta Genet. Statist. Med. 12: 33-40, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14464774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14464774</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14464774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Malik2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Malik, S., Kakar, N., Hasnain, S., Ahmad, J., Wilcox, E. R., Naz, S.
|
|
<strong>Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan.</strong>
|
|
Clin. Genet. 78: 247-256, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20184620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20184620</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20184620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2010.01375.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Murray1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murray, J. C., Nishimura, D., Ardinger, H., Buetow, K., Spence, A., Falk, R., Falk, P., Sparkes, R., Gardner, R. J. M., Glinski, L., Pauli, R., Nakamura, Y., Green, P., Yamada, Y.
|
|
<strong>Linkage of van der Woude syndrome to markers on chromosome 1q and exclusion of laminin B2 as a candidate gene. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 43: A153 only, 1988.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Murray1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murray, J. C., Nishimura, D. Y., Buetow, K. H., Ardinger, H. H., Spence, M. A., Sparkes, R. S., Falk, R. E., Falk, P. M., Gardner, R. J. M., Harkness, E. M., Glinski, L. P., Pauli, R. M., Nakamura, Y., Green, P. P., Schinzel, A.
|
|
<strong>Linkage of an autosomal dominant clefting syndrome (van der Woude) to loci on chromosome 1q.</strong>
|
|
Am. J. Hum. Genet. 46: 486-491, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309700</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2309700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Nishimura1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nishimura, D. Y., Buetow, K. H., Spence, M. A., Gardner, R. J. M., Pauli, R., Nakamura, Y., Green, P., Schinzel, A., Murray, J. C.
|
|
<strong>Linkage of van der Woude syndrome (LPS) to renin on 1q. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1053 only, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Nopoulos2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nopoulos, P., Berg, S., Canady, J., Richman, L., Van Demark, D., Andreasen, N. C.
|
|
<strong>Structural brain abnormalities in adult males with clefts of the lip and/or palate.</strong>
|
|
Genet. Med. 4: 1-9, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11839951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11839951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11839951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00125817-200201000-00001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Nopoulos2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nopoulos, P., Richman, L., Andreasen, N. C., Murray, J. C., Schutte, B.
|
|
<strong>Abnormal brain structure in adults with Van der Woude syndrome.</strong>
|
|
Clin. Genet. 71: 511-517, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17539900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17539900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17539900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00799.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Ranta1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ranta, R., Rintala, A. E.
|
|
<strong>Correlations between microforms of the van der Woude syndrome and cleft palate.</strong>
|
|
Cleft Palate J. 20: 158-162, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6573981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6573981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6573981" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Sander1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sander, A., Schmelzle, R., Murray, J.
|
|
<strong>Evidence for a microdeletion in 1q32-41 involving the gene responsible for van der Woude syndrome.</strong>
|
|
Hum. Molec. Genet. 3: 575-578, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/3.4.575" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Schinzel1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schinzel, A., Klausler, M.
|
|
<strong>The van der Woude syndrome (dominantly inherited lip pits and clefts).</strong>
|
|
J. Med. Genet. 23: 291-294, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3746828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3746828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3746828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.23.4.291" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Schneider1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneider, E. L.
|
|
<strong>Lip pits and congenital absence of second premolars: varied expression of the lip pits syndrome.</strong>
|
|
J. Med. Genet. 10: 346-349, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4272740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4272740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4272740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.10.4.346" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Schutte1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schutte, B. C., Basart, A. M., Watanabe, Y., Laffin, J. J. S., Coppage, K., Bjork, B. C., Daack-Hirsch, S., Patil, S., Dixon, M. J., Murray, J. C.
|
|
<strong>Microdeletions at chromosome bands 1q32-q41 as a cause of van der Woude syndrome.</strong>
|
|
Am. J. Med. Genet. 84: 145-150, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10323740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8628(19990521)84:2<145::aid-ajmg11>3.0.co;2-l" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Schutte1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schutte, B. C., Sander, A., Malik, M., Murray, J. C.
|
|
<strong>Refinement of the van der Woude gene location and construction of a 3.5-Mb YAC contig and STS map spanning the critical region in 1q32-q41.</strong>
|
|
Genomics 36: 507-514, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8884274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8884274</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8884274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0496" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Sertie1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sertie, A. L., Sousa, A. V., Steman, S., Pavanello, R. C., Passos-Bueno, M. R.
|
|
<strong>Linkage analysis in a large Brazilian family with van der Woude syndrome suggests the existence of a susceptibility locus for cleft palate at 17p11.2-11.1.</strong>
|
|
Am. J. Hum. Genet. 65: 433-440, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302491" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Shprintzen1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shprintzen, R. J., Goldberg, R. B., Sidoti, E. J.
|
|
<strong>The penetrance and variable expression of the van der Woude syndrome: implications for genetic counseling.</strong>
|
|
Cleft Palate J. 17: 52-57, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6928118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6928118</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6928118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Soricelli1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Soricelli, D. A., Bell, L., Alexander, W. A.
|
|
<strong>Congenital fistulas of the lower lip: a family case report.</strong>
|
|
Oral Surg. 21: 511-516, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5218157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5218157</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5218157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0030-4220(66)90410-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Test1947" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Test, A. R., Falls, H. F.
|
|
<strong>Dominant inheritance of cleft lip and palate in five generations.</strong>
|
|
J. Oral Surg. 5: 292-297, 1947.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18897035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18897035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18897035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="van der Woude1954" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van der Woude, A.
|
|
<strong>Fistula labii inferioris congenita and its association with cleft lip and palate.</strong>
|
|
Am. J. Hum. Genet. 6: 244-256, 1954.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13158329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13158329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13158329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Watanabe2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Watanabe, Y., Murray, J. C., Bjork, B. C., Bird, C. P., Chiang, P.-W., Gregory, S. G., Kurnit, D. M., Schutte, B. C.
|
|
<strong>Matroshka and ectopic polymorphisms: two new classes of DNA sequence variation identified at the van der Woude syndrome locus on 1q32-q41.</strong>
|
|
Hum. Mutat. 18: 422-434, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1213" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Wienker1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wienker, T. F., Hudek, G., Bissbort, S., Mayerova, A., Mauff, G., Bender, K.
|
|
<strong>Linkage studies in a pedigree with van der Woude syndrome.</strong>
|
|
J. Med. Genet. 24: 160-161, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3572998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3572998</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3572998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.24.3.160" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Wong2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wong, F. K., Koillinen, H., Rautio, J., Teh, B. T., Ranta, R., Karsten, A., Larson, O., Linder-Aronson, S., Huggare, J., Larsson, C., Kere, J.
|
|
<strong>Genetic heterogeneity and exclusion of a modifying locus at 17p11.2-p11.1 in Finnish families with van der Woude syndrome.</strong>
|
|
J. Med. Genet. 38: 198-202, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11303516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11303516</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11303516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.38.3.198" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Yeetong2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yeetong, P., Mahatumarat, C., Siriwan, P., Rojvachiranonda, N., Suphapeetiporn, K., Shotelersuk, V.
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<strong>Three novel mutations of the IRF6 gene with one associated with an unusual feature in van der Woude syndrome.</strong>
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Am. J. Med. Genet. 149A: 2489-2492, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19842205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19842205</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19842205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33048" 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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Marla J. F. O'Neill - updated : 8/15/2014
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Marla J. F. O'Neill - updated : 3/11/2014<br>Marla J. F. O'Neill - updated : 2/21/2013<br>Marla J. F. O'Neill - updated : 4/6/2011<br>Nara Sobreira - updated : 11/24/2009<br>Marla J. F. O'Neill - updated : 4/30/2008<br>Cassandra L. Kniffin - updated : 7/10/2007<br>Victor A. McKusick - updated : 9/4/2002<br>Michael J. Wright - updated : 4/26/2002<br>Victor A. McKusick - updated : 3/7/2002<br>Michael B. Petersen - updated : 2/25/2002<br>Victor A. McKusick - updated : 11/29/2001<br>Victor A. McKusick - updated : 11/14/2001<br>Sonja A. Rasmussen - updated : 4/13/2000<br>Michael J. Wright - updated : 3/22/2000<br>Victor A. McKusick - updated : 2/28/2000<br>Wilson H. Y. Lo - updated : 2/10/2000<br>Victor A. McKusick - updated : 1/12/2000<br>Moyra Smith - updated : 1/11/1997
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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alopez : 08/16/2024
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alopez : 03/22/2022<br>carol : 03/21/2022<br>carol : 12/29/2021<br>carol : 10/20/2015<br>carol : 8/18/2014<br>mcolton : 8/15/2014<br>alopez : 3/11/2014<br>carol : 2/21/2013<br>carol : 10/14/2011<br>wwang : 4/19/2011<br>terry : 4/6/2011<br>carol : 11/24/2009<br>wwang : 5/9/2008<br>terry : 4/30/2008<br>wwang : 1/7/2008<br>wwang : 7/18/2007<br>ckniffin : 7/10/2007<br>alopez : 10/18/2002<br>alopez : 9/16/2002<br>alopez : 9/6/2002<br>tkritzer : 9/4/2002<br>tkritzer : 9/4/2002<br>alopez : 4/26/2002<br>cwells : 3/18/2002<br>cwells : 3/14/2002<br>terry : 3/7/2002<br>carol : 2/25/2002<br>carol : 2/25/2002<br>cwells : 12/7/2001<br>cwells : 12/5/2001<br>terry : 11/29/2001<br>terry : 11/14/2001<br>mcapotos : 4/14/2000<br>terry : 4/13/2000<br>alopez : 3/22/2000<br>alopez : 3/22/2000<br>mgross : 3/15/2000<br>terry : 2/28/2000<br>mgross : 2/15/2000<br>carol : 2/14/2000<br>yemi : 2/11/2000<br>terry : 1/12/2000<br>carol : 10/25/1999<br>mark : 1/11/1997<br>jamie : 1/8/1997<br>mimadm : 6/25/1994<br>jason : 6/17/1994<br>carol : 4/10/1992<br>supermim : 3/16/1992<br>carol : 3/2/1992<br>carol : 6/24/1991
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<span class="mim-font">
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<strong>#</strong> 119300
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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VAN DER WOUDE SYNDROME 1; VWS1
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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VDWS<br />
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LIP-PIT SYNDROME; LPS; PIT<br />
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CLEFT LIP AND/OR PALATE WITH MUCOUS CYSTS OF LOWER LIP
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<strong>SNOMEDCT:</strong> 79261008;
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<strong>ICD10CM:</strong> Q38.0;
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<strong>ORPHA:</strong> 888;
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<strong>DO:</strong> 0060239;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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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 <br /> MIM number
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<span class="mim-font">
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1q32.2
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<span class="mim-font">
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van der Woude syndrome 1
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<span class="mim-font">
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119300
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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IRF6
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<span class="mim-font">
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607199
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<span class="mim-font">
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because van der Woude syndrome-1 (VWS1) is caused by heterozygous mutation in the gene encoding interferon regulatory factor-6 (IRF6; 607199) on chromosome 1q32.</p>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, and cleft lip and/or cleft palate (CL/P, CP). It is the most common cleft syndrome.</p><p><strong><em>Genetic Heterogeneity of van der Woude Syndrome</em></strong></p><p>
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Also see VWS2 (606713), caused by mutation in the GRHL3 gene (608317) on chromosome 1p36.</p>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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<span class="mim-text-font">
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<p>In 3 generations of a family, Levy (1962) found malformations of the lower lip consisting of symmetrical lumps. Two sibs had cleft palate in addition to the lip anomaly. The literature on this syndrome was analyzed by van der Woude (1954), who found confirmation for the autosomal dominant mode of inheritance. It is possible that in some affected families, because of the variable expressivity of the gene, the syndrome is expressed only as pits. Baker (1964) reported such a pedigree with affected members in 3 generations showing pits as the only malformation. On the other hand, only harelip and/or cleft palate without pits could segregate in families as a dominant trait. Test and Falls (1947) described the condition transmitted through 5 generations. </p><p>The rule that cleft palate alone and cleft lip with or without cleft palate behave differently does not hold in this disorder, in which either type of cleft alone or the 2 in combination may occur. Janku et al. (1980) traced the van der Woude syndrome through 7 generations. Lip pits, the most common manifestation, were present in 88% of the affected and were the only manifestation in 64%. Clefts of lip and palate occurred in 21%. Penetrance was 96.7%. </p><p>Ranta and Rintala (1983) analyzed the 'microforms' of the van der Woude syndrome in cases of cleft palate. Conical elevations (CE) on the lower lip at the site of sinuses were present in 39.3% of cleft palate cases, 0.8% of cleft lip with or without cleft palate cases, and 0.7% of noncleft cases. In CP cases with CE, the familial occurrence of clefts was statistically higher (30%) than in CP cases without CE. The corresponding figures for hypodontia were 40.7% and 24.7%, respectively. See review by Schinzel and Klausler (1986). </p><p>Burdick et al. (1987) reported 2 unrelated families from the area of Beijing, China. Ankyloglossia was found in the proband in each family. Soricelli et al. (1966) also described this association. </p><p>Kocer et al. (2001) described a child with symmetrical lower lip pits and cleft palate whose mother had only a single lower lip pit in the right paramedian region. (The possibility of mosaicism in the mother might be raised. VAM) </p><p>Birnbaum et al. (2008) analyzed the IRF6 gene in 63 families with what was believed to be isolated CL/P or CP and identified a deletion/insertion and duplication in 2 families, respectively. Despite 'credible denials' of a history of lip pits in family members, upon reinterviewing and retrieval of preoperative photographs, the presence of lip pits in both families confirmed the diagnosis of VWS. Birnbaum et al. (2008) noted that this is important for genetic counseling, because the recurrence risk of VWS is higher than the recurrence risk for nonsyndromic clefts. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Other Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nopoulos et al. (2007) reported brain MRI results in 7 adult men and 7 adult women with VWS. Seven of the affected patients belonged to a single large kindred; the remaining patients each came from a different family. Individuals with VWS had markedly larger gray matter volumes of the anterior cerebrum compared to controls, and there was a negative correlation between anterior gray matter volume and IQ, indicating that the changes had functional significance. Men with VWS also had decreased volumes of the posterior cerebrum. Nopoulos et al. (2007) concluded that brain structure is altered in individuals with VWS, similar to that observed in patients with isolated cleft lip/palate (see 119530 and Nopoulos et al., 2002), suggesting that both disorders reflect abnormal brain development. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cytogenetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bocian and Walker (1987) described a patient with an interstitial deletion of chromosome 1q, del(1q32-q41). Among other anomalies, the patient had congenital lower lip pits similar to those found in association with the van der Woude syndrome and with the popliteal pterygium syndrome. Bocian and Walker (1987) suggested that the van der Woude syndrome may be due to a submicroscopic deletion of chromosome 1q in the area stated. A tentative assignment of the locus, symbolized PIT, to 1q32-q41 was made on the basis of this report. Sander et al. (1994) reported a microdeletion involving 1q32-q41 in a family with VWS. They found allelic loss of the stable and highly polymorphic microsatellite D1S205. They estimated that the upper bound of the size of the deletion was 4 Mb. </p><p>Schutte et al. (1999) screened a panel of 37 VWS families for loss of transmission of an allele using a highly polymorphic marker (D1S3753) from the VWS critical region. Allele loss, indicating the presence of a deletion, was identified in 1 family. In this family, the phenotype in 3 generations of affected individuals was confined to the cardinal signs of VWS, in contrast to previously reported deletions in which developmental delay and other anomalies accompanied features of VWS (Bocian and Walker, 1987; Sander et al., 1994). Houdayer et al. (2000) performed a microsatellite-based screening test for 1q32-q41 haploinsufficiency on 14 family triads with VWS and identified no additional microdeletions. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wienker et al. (1987) excluded linkage of VDWS with a considerable number of marker loci in studies of a kindred segregating for the disorder through 5 generations. Only linkage with Duffy blood group (110700) showed a uniformly positive lod score (lod = 1.31 at theta = 0.0). Murray et al. (1988) found linkage of LPS to the renin gene (REN; 179820); lod = 4.62 at theta = 0.04. Studies by Nishimura et al. (1989) raised the maximum lod score to 8.62 at theta = 0.02 for linkage of LPS and REN. Murray et al. (1988) and Nishimura et al. (1989) also adopted a candidate gene approach and investigated whether the laminin B2 (150290) gene might be the site of the mutation in VDWS. The finding of several recombinants ruled out this possibility. Nishimura et al. (1989) used the same approach to investigate decay accelerating factor (125240) as the site of the mutation and found no recombinants (lod = 2.22). Murray et al. (1990) reported a multipoint linkage analysis that indicated flanking of the VDWS locus by REN and D1S65 at a lod score of 10.83. </p><p>Schutte et al. (1996) constructed a 3.5-Mb YAC contig and sequence tagged site (STS) map extending from D1S245 to D1S414 in the region containing the VWS locus. They also carried out deletion mapping on a somatic cell hybrid derived from a patient with VWS due to a microdeletion. Analysis of this hybrid and genetic analysis in an additional family narrowed the VWS critical region to a 1.6-cM region flanked by D1S491 and D1S205. The authors noted that the STS markers that flank this critical region and the proximal and distal ends of the microdeletion are present in a single 850-kb YAC. </p><p>Houdayer et al. (1999) studied the linkage of 6 microsatellite markers in the 1q32-q41 region to the disease phenotype in 5 Caucasian VWS kindreds. A maximum cumulative lod score of 3.27 at a recombination fraction of 0.00 was obtained with marker D1S245. The inner 4 markers were found to be tightly linked to one another without recombination. The authors concluded that the results favored locus homogeneity. </p><p>In studies of 4 multiplex Caucasian VWS families that had been recruited at 3 different locations in the U.S., Beiraghi et al. (1999) found positive lod scores without any recombination in the candidate region of 1q. The largest 2-point lod score was 5.87. They used an assay method for short tandem repeat (STR) markers that provided highly accurate size estimation of marker allele fragment sizes, enabling them to determine the specific alleles segregating with the VWS gene in each of the 4 families. They observed a striking pattern of STR allele sharing at several closely linked loci among the 4 VWS families. These results suggested the possibility of a unique (i.e., single) origin for the mutation responsible for many or most cases of VWS. </p><p>Lees et al. (1999) reported clinical features and linkage analysis in 3 families with popliteal pterygium syndrome. Linkage analysis showed a multipoint lod score of 2.7 with no evidence of recombination using the markers D1S205, D1S491, and D1S3753 in the critical region for VWS on chromosome 1q32, supporting the hypothesis that these 2 conditions are allelic. </p><p>The cardinal features of van der Woude syndrome are lip pits and cleft lip with or without cleft palate or cleft palate (alone) (119540). Since none of these traits is present in all mutation carriers, some individuals or familial VWS cases, especially those lacking lip pits, are indiscernible from nonsyndromic CL/P (119530), raising the question of whether allelic variation at the VWS locus could underlie nonsyndromic CL/P. Houdayer et al. (2001) addressed this question using parametric linkage (lod score) analysis in 21 multiplex nonsyndromic CL/P families based on a tightly linked microsatellite marker (D1S3753) and nonparametric analysis using the transmission/disequilibrium test in 106 nonsyndromic CL/P triads (2 parents and an offspring) and 3 selecting markers on chromosome 1. No evidence for linkage of nonsyndromic CL/P to VWS was found on the 21 families using the lod score approach. In contrast, the transmission/disequilibrium test yielded a significant P value of 0.04 for D1S205, supporting involvement of VWS in nonsyndromic CL/P in a complex, modifying/polygenic manner rather than as a monogenic/major disease locus. </p><p>Wong et al. (2001) performed linkage analysis in 5 Finnish families with VWS. Three of these families were linked to the 1q32-q41 region. A recombination in an unaffected individual reduced the critical region to a 200-kb interval bounded by the markers at D1S491 and D1S3753. The authors expressed caution about the use of apparently unaffected individuals in a condition with low expressivity. Linkage disequilibrium suggested that the critical region was 130 kb bounded by the markers at D1S491 and D1S2136. </p><p><strong><em>Modifier Loci</em></strong></p><p>
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The expression of VWS, which has incomplete penetrance, is highly variable. Both the occurrence of cleft lip/palate and cleft palate within the same kindred and a recurrence risk of less than 40% for cleft palate among descendants with VWS suggested that the development of clefts in this syndrome is influenced by modifying genes at other loci. To test this hypothesis, Sertie et al. (1999) conducted linkage analysis in a large Brazilian kindred with VWS, considering as affected the individuals with CP, regardless of whether it was associated with other clinical signs of VWS. The results suggested that a gene at 17p11.2-p11.1 (604547), together with the VWS gene at 1q32, enhances the probability of CP in an individual carrying the 2 at-risk genes. Sertie et al. (1999) stated that if this hypothesis is confirmed in other VWS pedigrees, it will represent one of the first examples of a gene, mapped through linkage analysis, that modifies the expression of a major gene. </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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<span class="mim-text-font">
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<p>The transmission pattern of VWS1 in the families reported by Kondo et al. (2002) was consistent with autosomal dominant inheritance. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>In efforts to clone the VWS gene, Watanabe et al. (2001) analyzed 900 kb of genomic sequence from the critical region of 1q32-q41. They found a polymorphism within a polymorphism that is a deletion/insertion (del/ins) polymorphism with a TTCC short tandem repeat (STR) embedded within it. They suggested that this be called a 'matroshka' polymorphism, after the Russian doll that has additional dolls nested inside. </p><p>Kondo et al. (2002) performed direct sequence analysis of genes and presumptive transcripts in the 350-kb VWS critical region identified by linkage analysis and identified mutations in the IRF6 gene, encoding interferon regulatory factor-6. They found a nonsense mutation in exon 4 of the IRF6 gene (607199.0001) in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, they identified mutations in 45 additional unrelated families with VWS and distinct mutations in 13 families with popliteal pterygium syndrome (119500). In a family whose affected members showed cleft lip with or without cleft palate and isolated cleft palate, Kondo et al. (2002) found that all affected members regardless of phenotype shared the 18-bp deletion (607199.0002) found in the proband. The authors hypothesized that marked phenotypic variation in their cohort strongly implicated the action of stochastic factors or modifier genes on IRF6 function. </p><p>Ghassibe et al. (2004) screened the IRF6 gene in 6 families with VWS and identified 6 heterozygous missense mutations, respectively, all affecting either the DNA-binding or the protein-binding domain. In a 4-generation VWS family in which affected individuals carried an L22P mutation (607199.0014), 2 of the patients displayed additional features: 1 had finger syndactyly, and the other had toe syndactyly and oral synechiae. Ghassibe et al. (2004) stated that because syndactyly and synechiae are major signs for PPS, these 2 patients were considered to have PPS, whereas the 6 other affected family members were classified as VWS, thus demonstrating that a single mutation could be responsible for both syndromes. </p><p>Yeetong et al. (2009) reported 3 female patients with lower lip anomalies, all of whom had heterozygous mutations in the IRF6 gene. One patient was a 16-year-old girl with bilateral conical elevations without pits, joining at the midline of the lower lip, giving the appearance of a heart-shaped mass; she was heterozygous for a nonsense mutation (Q49X; 607199.0017). Her mother and other relatives were reported to have similar findings, but were unavailable for evaluation. </p><p>Malik et al. (2010) identified 16 Pakistani probands with VWS from more than 1,200 individuals with CL/P, for a frequency of approximately 1% in Pakistan. Analysis of IRF6 in the 16 VWS probands identified mutations in 12 of them (see, e.g., 607199.0009 and 607199.0018), including 2 missense mutations that previously had been identified in patients with popliteal pterygium syndrome (PPS). While no clinical signs of PPS were identified or reported by these patients or their families, Malik et al. (2010) noted that subtler signs of PPS such as genital hypoplasia may have been present but were not evaluated in this study. </p><p>To test whether DNA variants in regulatory elements cause VWS, Fakhouri et al. (2014) sequenced 3 conserved elements near IRF6 in 70 VWS families who were negative for mutations with IRF6 exons and identified a duplication (350dupA) within a highly conserved sequence in the MCS9.7 enhancer element in a 3-generation Brazilian family. The duplication was present in 3 affected individuals as well as in 2 unaffected family members, but it was not found in 100 unaffected controls or in 1,092 genomes from 14 populations in the NHLBI Exome Sequencing Project database. Functional analysis demonstrated that the 350dupA mutation disrupted MCS9.7 enhancer activity in 2 different cell lines as well as in vivo in a transgenic mouse embryo assay. </p><p><strong><em>Van der Woude Syndrome-Popliteal Pterygium Syndrome Spectrum</em></strong></p><p>
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In a patient with overlapping features of VWS and PPS (unilateral cleft lip and palate, ankyloblepharon, paramedian lip pits) as well as unilateral renal aplasia and coronal hypospadias, de Medeiros et al. (2008) identified a novel heterozygous mutation in the IRF6 gene (607199.0013). The patient and his brother, who had hypospadias and nephrocalcinosis but no IRF6 mutation, were both conceived by in vitro fertilization. De Medeiros et al. (2008) suggested that the hypospadias and renal aplasia may have been due to the method of fertilization rather than the IRF6 mutation. They noted that a lethal PPS syndrome (263650) has renal aplasia as a feature. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between van der Woude syndrome and mutation in the CFAP57 gene, see 614259.0001.</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>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Bowers (1970); Burdick et al. (1985); Cervenka et al. (1967); Eastman
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et al. (1978); Schneider (1973); Shprintzen et al. (1980)
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Baker, B. R.
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<strong>A family with bilateral congenital pits of the inferior lip.</strong>
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Oral Surg. 18: 494-497, 1964.
|
|
|
|
|
|
[PubMed: 14198088]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0030-4220(64)90398-6]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Beiraghi, S., Miller-Chisholm, A., Kimberling, W. J., Sun, C., Wang, Y.-F., Russell, L. J., Khoshnevisan, M. H., Storm, A. L., Long, R. E., Jr., Witt, P. D., Mazaheri, M., Diehl, S. R.
|
|
<strong>Confirmation of linkage of van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation.</strong>
|
|
J. Craniofac. Genet. Dev. Biol. 19: 128-134, 1999.
|
|
|
|
|
|
[PubMed: 10589394]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Birnbaum, S., Reutter, H., Lauster, C., Scheer, M., Schmidt, G., Saffar, M., Martini, M., Hemprich, A., Henschke, H., Kramer, F.-J., Mangold, E.
|
|
<strong>Mutation screening in the IRF6-gene in patients with apparently nonsyndromic orofacial clefts and a positive family history suggestive of autosomal-dominant inheritance.</strong>
|
|
Am. J. Med. Genet. 146A: 787-790, 2008.
|
|
|
|
|
|
[PubMed: 18247422]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32219]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bocian, M., Walker, A. P.
|
|
<strong>Lip pits and deletion 1q32-q41.</strong>
|
|
Am. J. Med. Genet. 26: 437-443, 1987.
|
|
|
|
|
|
[PubMed: 3812594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320260223]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowers, D. G.
|
|
<strong>Congenital lower lip sinuses with cleft palate.</strong>
|
|
Plast. Reconst. Surg. 45: 151-154, 1970.
|
|
|
|
|
|
[PubMed: 5411896]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00006534-197002000-00008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burdick, A. B., Bixler, D., Puckett, C. L.
|
|
<strong>Genetic analysis in families with van der Woude syndrome.</strong>
|
|
J. Craniofac. Genet. Dev. Biol. 5: 181-208, 1985.
|
|
|
|
|
|
[PubMed: 4019732]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burdick, A. B., Ma, L. A., Zhuohua, D., Ning, G.
|
|
<strong>van der Woude syndrome in two families in China.</strong>
|
|
J. Craniofac. Genet. Dev. Biol. 7: 413-418, 1987.
|
|
|
|
|
|
[PubMed: 3429616]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cervenka, J., Gorlin, R. J., Anderson, V. E.
|
|
<strong>The syndrome of pits of the lower lip and cleft lip and/or palate: genetic considerations.</strong>
|
|
Am. J. Hum. Genet. 19: 416-432, 1967.
|
|
|
|
|
|
[PubMed: 6026934]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Medeiros, F., Hansen, L., Mawlad, E., Eiberg, H., Asklund, C., Tommerup, N., Jakobsen, L. P.
|
|
<strong>A novel mutation in IRF6 resulting in VWS-PPS spectrum disorder with renal aplasia.</strong>
|
|
Am. J. Med. Genet. 146A: 1605-1608, 2008.
|
|
|
|
|
|
[PubMed: 18478600]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32257]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eastman, J. R., Bixler, D., Escobar, V.
|
|
<strong>Linkage studies in van der Woude syndrome.</strong>
|
|
J. Med. Genet. 15: 217-281, 1978.
|
|
|
|
|
|
[PubMed: 671486]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.15.3.217]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fakhouri, W. D., Rahimov, F., Attanasio, C., Kouwenhoven, E. N., Ferreira De Lima, R. L., Felix, T. M., Nitschke, L., Huver, D., Barrons, J., Kousa, Y. A., Leslie, E., Pennacchio, L. A., Van Bokhoven, H., Visel, A., Zhou, H., Murray, J. C., Schutte, B. C.
|
|
<strong>An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects.</strong>
|
|
Hum. Molec. Genet. 23: 2711-2720, 2014.
|
|
|
|
|
|
[PubMed: 24442519]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddt664]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ghassibe, M., Revencu, N., Bayet, B., Gillerot, Y., Vanwijck, R., Verellen-Dumoulin, C., Vikkula, M.
|
|
<strong>Six families with van der Woude and/or popliteal pterygium syndrome: all with a mutation in the IRF6 gene.</strong>
|
|
J. Med. Genet. 41: e15, 2004. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 14757865]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2003.009274]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Houdayer, C., Bonaiti-Pellie, C., Erguy, C., Soupre, V., Dondon, M.-G., Burglen, L., Cougoureux, E., Couderc, R., Vazquez, M.-P., Bahuau, M.
|
|
<strong>Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).</strong>
|
|
Am. J. Med. Genet. 104: 86-92, 2001.
|
|
|
|
|
|
[PubMed: 11746036]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1096-8628(20011115)104:1<86::aid-ajmg10053>3.0.co;2-e]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Houdayer, C., Soupre, V., Karcenty, B., Vazquez, M.-P., Odent, S., Lacombe, D., Le Bouc, Y., Munnich, A., Bahuau, M.
|
|
<strong>1q32-q41 microdeletion with reference to van der Woude syndrome and allied clefting entities. (Letter)</strong>
|
|
Am. J. Med. Genet. 91: 161-163, 2000.
|
|
|
|
|
|
[PubMed: 10748420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(20000313)91:2<161::aid-ajmg18>3.0.co;2-q]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Houdayer, C., Soupre, V., Rosenberg-Bourgin, M., Martinez, H., Tredano, M., Feldmann, D., Feingold, J., Aymard, P., Munnich, A., Le Bouc, Y., Vazquez, M. P., Bahuau, M.
|
|
<strong>Linkage analysis of 5 novel van der Woude syndrome kindreds to 1q32-q41 markers further supports locus homogeneity of the disease trait.</strong>
|
|
Ann. Genet. 42: 69-74, 1999.
|
|
|
|
|
|
[PubMed: 10434119]
|
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|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janku, P., Robinow, M., Kelly, T., Bralley, R., Baynes, A., Edgerton, M. T.
|
|
<strong>The van der Woude syndrome in a large kindred: variability, penetrance, genetic risks.</strong>
|
|
Am. J. Med. Genet. 5: 117-123, 1980.
|
|
|
|
|
|
[PubMed: 7395906]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320050203]
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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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Kocer, U., Aksoy, H. M., Tiftikcioglu, Y. O., Cologlu, H., Karaaslan, O.
|
|
<strong>Report of two cases with van der Woude syndrome: a child and her mother.</strong>
|
|
Genet. Counsel. 12: 341-346, 2001.
|
|
|
|
|
|
[PubMed: 11837602]
|
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|
|
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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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Kondo, S., Schutte, B. C., Richardson, R. J., Bjork, B. C., Knight, A. S., Watanabe, Y., Howard, E., Ferreira de Lima, R. L. L., Daack-Hirsch, S., Sander, A., McDonald-McGinn, D. M., Zackai, E. H., and 14 others.
|
|
<strong>Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. (Letter)</strong>
|
|
Nature Genet. 32: 285-289, 2002.
|
|
|
|
|
|
[PubMed: 12219090]
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|
|
|
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[Full Text: https://doi.org/10.1038/ng985]
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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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Lees, M. M., Winter, R. M., Malcolm, S., Saal, H. M., Chitty, L.
|
|
<strong>Popliteal pterygium syndrome: a clinical study of three families and report of linkage to the van der Woude syndrome locus on 1q32.</strong>
|
|
J. Med. Genet. 36: 888-892, 1999.
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[PubMed: 10593995]
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<p class="mim-text-font">
|
|
Levy, J.
|
|
<strong>Zwillinge in einer Familie mit Unterlippenmissbildung.</strong>
|
|
Acta Genet. Statist. Med. 12: 33-40, 1962.
|
|
|
|
|
|
[PubMed: 14464774]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Malik, S., Kakar, N., Hasnain, S., Ahmad, J., Wilcox, E. R., Naz, S.
|
|
<strong>Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan.</strong>
|
|
Clin. Genet. 78: 247-256, 2010.
|
|
|
|
|
|
[PubMed: 20184620]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01375.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murray, J. C., Nishimura, D., Ardinger, H., Buetow, K., Spence, A., Falk, R., Falk, P., Sparkes, R., Gardner, R. J. M., Glinski, L., Pauli, R., Nakamura, Y., Green, P., Yamada, Y.
|
|
<strong>Linkage of van der Woude syndrome to markers on chromosome 1q and exclusion of laminin B2 as a candidate gene. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 43: A153 only, 1988.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murray, J. C., Nishimura, D. Y., Buetow, K. H., Ardinger, H. H., Spence, M. A., Sparkes, R. S., Falk, R. E., Falk, P. M., Gardner, R. J. M., Harkness, E. M., Glinski, L. P., Pauli, R. M., Nakamura, Y., Green, P. P., Schinzel, A.
|
|
<strong>Linkage of an autosomal dominant clefting syndrome (van der Woude) to loci on chromosome 1q.</strong>
|
|
Am. J. Hum. Genet. 46: 486-491, 1990.
|
|
|
|
|
|
[PubMed: 2309700]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishimura, D. Y., Buetow, K. H., Spence, M. A., Gardner, R. J. M., Pauli, R., Nakamura, Y., Green, P., Schinzel, A., Murray, J. C.
|
|
<strong>Linkage of van der Woude syndrome (LPS) to renin on 1q. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1053 only, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nopoulos, P., Berg, S., Canady, J., Richman, L., Van Demark, D., Andreasen, N. C.
|
|
<strong>Structural brain abnormalities in adult males with clefts of the lip and/or palate.</strong>
|
|
Genet. Med. 4: 1-9, 2002.
|
|
|
|
|
|
[PubMed: 11839951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00125817-200201000-00001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nopoulos, P., Richman, L., Andreasen, N. C., Murray, J. C., Schutte, B.
|
|
<strong>Abnormal brain structure in adults with Van der Woude syndrome.</strong>
|
|
Clin. Genet. 71: 511-517, 2007.
|
|
|
|
|
|
[PubMed: 17539900]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00799.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ranta, R., Rintala, A. E.
|
|
<strong>Correlations between microforms of the van der Woude syndrome and cleft palate.</strong>
|
|
Cleft Palate J. 20: 158-162, 1983.
|
|
|
|
|
|
[PubMed: 6573981]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sander, A., Schmelzle, R., Murray, J.
|
|
<strong>Evidence for a microdeletion in 1q32-41 involving the gene responsible for van der Woude syndrome.</strong>
|
|
Hum. Molec. Genet. 3: 575-578, 1994.
|
|
|
|
|
|
[PubMed: 8069301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.4.575]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schinzel, A., Klausler, M.
|
|
<strong>The van der Woude syndrome (dominantly inherited lip pits and clefts).</strong>
|
|
J. Med. Genet. 23: 291-294, 1986.
|
|
|
|
|
|
[PubMed: 3746828]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.23.4.291]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneider, E. L.
|
|
<strong>Lip pits and congenital absence of second premolars: varied expression of the lip pits syndrome.</strong>
|
|
J. Med. Genet. 10: 346-349, 1973.
|
|
|
|
|
|
[PubMed: 4272740]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.10.4.346]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schutte, B. C., Basart, A. M., Watanabe, Y., Laffin, J. J. S., Coppage, K., Bjork, B. C., Daack-Hirsch, S., Patil, S., Dixon, M. J., Murray, J. C.
|
|
<strong>Microdeletions at chromosome bands 1q32-q41 as a cause of van der Woude syndrome.</strong>
|
|
Am. J. Med. Genet. 84: 145-150, 1999.
|
|
|
|
|
|
[PubMed: 10323740]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19990521)84:2<145::aid-ajmg11>3.0.co;2-l]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schutte, B. C., Sander, A., Malik, M., Murray, J. C.
|
|
<strong>Refinement of the van der Woude gene location and construction of a 3.5-Mb YAC contig and STS map spanning the critical region in 1q32-q41.</strong>
|
|
Genomics 36: 507-514, 1996.
|
|
|
|
|
|
[PubMed: 8884274]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0496]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sertie, A. L., Sousa, A. V., Steman, S., Pavanello, R. C., Passos-Bueno, M. R.
|
|
<strong>Linkage analysis in a large Brazilian family with van der Woude syndrome suggests the existence of a susceptibility locus for cleft palate at 17p11.2-11.1.</strong>
|
|
Am. J. Hum. Genet. 65: 433-440, 1999.
|
|
|
|
|
|
[PubMed: 10417286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302491]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shprintzen, R. J., Goldberg, R. B., Sidoti, E. J.
|
|
<strong>The penetrance and variable expression of the van der Woude syndrome: implications for genetic counseling.</strong>
|
|
Cleft Palate J. 17: 52-57, 1980.
|
|
|
|
|
|
[PubMed: 6928118]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soricelli, D. A., Bell, L., Alexander, W. A.
|
|
<strong>Congenital fistulas of the lower lip: a family case report.</strong>
|
|
Oral Surg. 21: 511-516, 1966.
|
|
|
|
|
|
[PubMed: 5218157]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0030-4220(66)90410-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Test, A. R., Falls, H. F.
|
|
<strong>Dominant inheritance of cleft lip and palate in five generations.</strong>
|
|
J. Oral Surg. 5: 292-297, 1947.
|
|
|
|
|
|
[PubMed: 18897035]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van der Woude, A.
|
|
<strong>Fistula labii inferioris congenita and its association with cleft lip and palate.</strong>
|
|
Am. J. Hum. Genet. 6: 244-256, 1954.
|
|
|
|
|
|
[PubMed: 13158329]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Watanabe, Y., Murray, J. C., Bjork, B. C., Bird, C. P., Chiang, P.-W., Gregory, S. G., Kurnit, D. M., Schutte, B. C.
|
|
<strong>Matroshka and ectopic polymorphisms: two new classes of DNA sequence variation identified at the van der Woude syndrome locus on 1q32-q41.</strong>
|
|
Hum. Mutat. 18: 422-434, 2001.
|
|
|
|
|
|
[PubMed: 11668635]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1213]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wienker, T. F., Hudek, G., Bissbort, S., Mayerova, A., Mauff, G., Bender, K.
|
|
<strong>Linkage studies in a pedigree with van der Woude syndrome.</strong>
|
|
J. Med. Genet. 24: 160-161, 1987.
|
|
|
|
|
|
[PubMed: 3572998]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.24.3.160]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wong, F. K., Koillinen, H., Rautio, J., Teh, B. T., Ranta, R., Karsten, A., Larson, O., Linder-Aronson, S., Huggare, J., Larsson, C., Kere, J.
|
|
<strong>Genetic heterogeneity and exclusion of a modifying locus at 17p11.2-p11.1 in Finnish families with van der Woude syndrome.</strong>
|
|
J. Med. Genet. 38: 198-202, 2001.
|
|
|
|
|
|
[PubMed: 11303516]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.38.3.198]
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</p>
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</li>
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<li>
|
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|
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Yeetong, P., Mahatumarat, C., Siriwan, P., Rojvachiranonda, N., Suphapeetiporn, K., Shotelersuk, V.
|
|
<strong>Three novel mutations of the IRF6 gene with one associated with an unusual feature in van der Woude syndrome.</strong>
|
|
Am. J. Med. Genet. 149A: 2489-2492, 2009.
|
|
|
|
|
|
[PubMed: 19842205]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33048]
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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