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Entry
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- #613554 - VON WILLEBRAND DISEASE, TYPE 2; VWD2
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- OMIM
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<p>
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<span class="h4">#613554</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/613554"><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="#inheritance">Inheritance</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#otherFeatures">Other Features</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#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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<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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</ul>
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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<div 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 id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://clinicaltrials.gov/search?cond=VON WILLEBRAND DISEASE, TYPE" 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="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17612&Typ=Pat" title="Von Willebrand disease type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Von Willebrand disease typ… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17613&Typ=Pat" title="Von Willebrand disease type 2A" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Von Willebrand disease typ… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17614&Typ=Pat" title="Von Willebrand disease type 2B" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Von Willebrand disease typ… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17615&Typ=Pat" title="Von Willebrand disease type 2M" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Von Willebrand disease typ… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17616&Typ=Pat" title="Von Willebrand disease type 2N" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Von Willebrand disease typ… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3497&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Von Willebrand disease </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK7014/" 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/9461" 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/von-willebrand-disease" 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=613554[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166081" title="Von Willebrand disease type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Von Willebrand disease typ…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166084" title="Von Willebrand disease type 2A" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Von Willebrand disease typ…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166087" title="Von Willebrand disease type 2B" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Von Willebrand disease typ…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166090" title="Von Willebrand disease type 2M" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Von Willebrand disease typ…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166093" title="Von Willebrand disease type 2N" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Von Willebrand disease typ…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Von Willebrand disease</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0060574" 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/613554" 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/OMIA001339/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0060574" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 128107007, 359711001, 359717002, 359732009<br />
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<strong>ICD10CM:</strong> D68.02, D68.020, D68.021, D68.022, D68.023, D68.029<br />
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 166081, 166084, 166087, 166090, 166093, 903<br />
|
|
|
|
|
|
<strong>DO:</strong> 0060574<br />
|
|
|
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|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
613554
|
|
</span>
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</span>
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</div>
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</div>
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<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
VON WILLEBRAND DISEASE, TYPE 2; VWD2
|
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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>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
VON WILLEBRAND DISEASE, TYPE II<br />
|
|
VWD, TYPE 2
|
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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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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
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|
</p>
|
|
</div>
|
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<div>
|
|
<span class="h3 mim-font">
|
|
VON WILLEBRAND DISEASE, TYPE 2A, INCLUDED; VWD2A, INCLUDED
|
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</span>
|
|
</div>
|
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|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
VON WILLEBRAND DISEASE, TYPE 2B, INCLUDED; VWD2B, INCLUDED<br />
|
|
VON WILLEBRAND DISEASE, TYPE 2M, INCLUDED; VWD2M, INCLUDED<br />
|
|
VON WILLEBRAND DISEASE, TYPE 2N, INCLUDED; VWD2N, INCLUDED
|
|
</span>
|
|
</div>
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/12/45?start=-3&limit=10&highlight=45">
|
|
12p13.31
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
von Willebrand disease, types 2A, 2B, 2M, and 2N
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613554"> 613554 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
VWF
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613160"> 613160 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/613554" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/613554" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613554" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- 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 /> -
|
|
Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Epistaxis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249366005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249366005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R04.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R04.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/784.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014591&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014591</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000421</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000421</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Easy bruising <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/425075004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">425075004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/424131007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">424131007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423798</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000978" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000978</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000978" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000978</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Prolonged bleeding due to a qualitative defect in the VWF protein <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552804&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552804</a>]</span><br /> -
|
|
Defect in platelet aggregation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855853&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855853</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003540</a>]</span><br /> -
|
|
Mucocutaneous bleeding <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3150070&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3150070</a>]</span><br /> -
|
|
Menorrhagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386692008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386692008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N92.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N92.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025323&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025323</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000132" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000132</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000132" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000132</a>]</span><br /> -
|
|
Patients with type 2B develop thrombocytopenia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552805&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552805</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Decreased levels of plasma factor VIII in patients with type 2N <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552803&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552803</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
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</span>
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Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
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Type 2CB is characterized by defective binding affinity for collagen types I and III<br />
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- Caused by mutation in the von Willebrand factor gene (VWF, <a href="/entry/613160#0001">613160.0001</a>)<br />
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>A number sign (#) is used with this entry because von Willebrand disease (VWD) type 2 is caused by mutation in the gene encoding von Willebrand factor (VWF; <a href="/entry/613160">613160</a>), which maps to chromosome 12p13.</p>
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<p>Von Willebrand disease is the most common inherited bleeding disorder. It is characterized clinically by mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. It results from a defect in platelet aggregation due to defects in the von Willebrand factor. Von Willebrand factor is a large, multimeric protein that plays a role in platelet adhesion and also serves as a carrier for the thrombotic protein factor VIII (F8; <a href="/entry/300841">300841</a>). F8 is mutated in hemophilia A (<a href="/entry/306700">306700</a>) (review by <a href="#11" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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>Whereas von Willebrand disease types 1 (<a href="/entry/193400">193400</a>) and 3 (<a href="/entry/277480">277480</a>) are characterized by quantitative defects in the VWF gene, von Willebrand disease type 2, which is divided in subtypes 2A, 2B, 2M, and 2N, is characterized by qualitative abnormalities of the VWF protein. The mutant VWF protein in types 2A, 2B, and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind F8. VWD2 accounts for 20 to 30% of cases of VWD (<a href="#27" class="mim-tip-reference" title="Mannucci, P. M. <strong>Treatment of von Willebrand's disease.</strong> New Eng. J. Med. 351: 683-694, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15306670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15306670</a>] [<a href="https://doi.org/10.1056/NEJMra040403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15306670">Mannucci, 2004</a>; <a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>; <a href="#25" class="mim-tip-reference" title="Lillicrap, D. <strong>Genotype/phenotype association in von Willebrand disease: is the glass half full or empty?</strong> J. Thromb. Haemost. 7 (suppl. 1): 65-70, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19630771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19630771</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2009.03367.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19630771">Lillicrap, 2009</a>; <a href="#11" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20409624+19630771+15306670+16889557" 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>For a general discussion and a classification of the types of von Willebrand disease, see VWD type 1 (<a href="/entry/193400">193400</a>).</p>
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<p>Von Willebrand disease type 2, like VWD type 1, is characterized by excessive mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery (<a href="#27" class="mim-tip-reference" title="Mannucci, P. M. <strong>Treatment of von Willebrand's disease.</strong> New Eng. J. Med. 351: 683-694, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15306670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15306670</a>] [<a href="https://doi.org/10.1056/NEJMra040403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15306670">Mannucci, 2004</a>). The delineation of different subtypes of VWD type 2 does not reflect clinical differences, but rather different mutant VWF protein phenotypes, which may affect diagnosis, treatment, and counseling (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15306670+16889557" 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>Inheritance of VWD type 2 is generally autosomal dominant, although some cases are characterized by autosomal recessive transmission (<a href="#27" class="mim-tip-reference" title="Mannucci, P. M. <strong>Treatment of von Willebrand's disease.</strong> New Eng. J. Med. 351: 683-694, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15306670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15306670</a>] [<a href="https://doi.org/10.1056/NEJMra040403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15306670">Mannucci, 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15306670" 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><strong><em>Von Willebrand Disease Type 2A</em></strong></p><p>
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The mutant VWF protein in von Willebrand disease type 2A has decreased platelet adhesion due to a selective deficiency of high molecular weight multimers. The decrease in large multimers can be due to (1) a failure to synthesize the multimers ('group 1') or (2) enhanced ADAMTS13 (<a href="/entry/604134">604134</a>)-mediated proteolysis of the secreted high molecular weight protein ('group 2'). Regardless of mechanism in type 2A, the loss of large multimers is associated with decreased VWF-platelet interactions and/or decreased VWF-connective tissue interactions (reviews by <a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a> and <a href="#25" class="mim-tip-reference" title="Lillicrap, D. <strong>Genotype/phenotype association in von Willebrand disease: is the glass half full or empty?</strong> J. Thromb. Haemost. 7 (suppl. 1): 65-70, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19630771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19630771</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2009.03367.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19630771">Lillicrap, 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19630771+16889557" 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>Historically, type 2A was subclassified into types IIA, IIC, IID, and IIE. The mutant VWF in type IIA showed increased proteolysis by ADAMTS13; type IIC showed impaired multimerization in the Golgi apparatus due to mutation in the VWF propeptide (<a href="#62" class="mim-tip-reference" title="Zimmerman, T. S., Ruggeri, Z. M. <strong>Von Willebrand disease.</strong> Hum. Path. 18: 140-152, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3100416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3100416</a>] [<a href="https://doi.org/10.1016/s0046-8177(87)80332-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3100416">Zimmerman and Ruggeri, 1987</a>); type IID showed impaired dimerization in the endoplasmic reticulum due to mutations in the C-terminal domain; and type IIE showed impaired intersubunit disulfide bond formation in the Golgi apparatus (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>) and a lack of outer proteolytic bands on gel electrophoresis, indicating reduced proteolysis (<a href="#61" class="mim-tip-reference" title="Zimmerman, T. S., Dent, J. A., Ruggeri, Z. M., Nannini, L. H. <strong>Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE).</strong> J. Clin. Invest. 77: 947-951, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485111</a>] [<a href="https://doi.org/10.1172/JCI112394" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3485111">Zimmerman et al., 1986</a>). All these subtypes showed dominant inheritance except for IIC, which showed recessive inheritance. These subtypes of type 2A are no longer used because the discrimination has not shown clinical utility; all are now referred to as type 2A (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3485111+16889557+3100416" 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="Gralnick, H. R., Williams, S. B., McKeown, L. P., Rick, M. E., Maisonneuve, P., Jenneau, C., Sultan, Y. <strong>Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.</strong> J. Clin. Invest. 76: 1522-1529, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2932469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2932469</a>] [<a href="https://doi.org/10.1172/JCI112132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2932469">Gralnick et al. (1985)</a> found that in VWD type 2A, inhibition of a calcium-dependent protease in vitro resulted in correction of the abnormal multimeric structure. This suggested that an abnormal VWF protein synthesized in this disorder is susceptible to proteolytic degradation, a process which may play an important role in phenotypic expression of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2932469" 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>Von Willebrand Disease Type 2B</em></strong></p><p>
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The mutant VWF protein in VWD type 2B shows increased affinity to platelet GP1BA (<a href="/entry/606672">606672</a>), resulting in increased platelet aggregation, and increased proteolysis of VWF subunits causing a decrease of large VWF multimers. Patients often have secondary thrombocytopenia due to platelet consumption (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" 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="#38" class="mim-tip-reference" title="Othman, M., Favaloro, E. J. <strong>Genetics of type 2B von Willebrand disease: 'true 2B,' 'tricky 2B,' or 'not 2B.' What are the modifiers of the phenotype?</strong> Semin. Thromb. Hemost. 34: 520-531, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19085651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19085651</a>] [<a href="https://doi.org/10.1055/s-0028-1103363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19085651">Othman and Favaloro (2008)</a> reviewed the complexity of VWD type 2B, noting that atypical forms with complete VWF monomers, no mutations in the A1 domain, or with giant platelets have also been reported, suggesting the presence of phenotypic modifiers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19085651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#46" class="mim-tip-reference" title="Saba, H. I., Saba, S. R., Dent, J., Ruggeri, Z. M., Zimmerman, T. S. <strong>Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.</strong> Blood 66: 282-286, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3926021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3926021</a>]" pmid="3926021">Saba et al. (1985)</a> found chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro in affected members of a family with VWD type 2B. The 4 affected family members identified were a man and 2 sons and a daughter by 2 different wives. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3926021" 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="Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M. <strong>Von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong> Blood 68: 668-672, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>]" pmid="3488775">Holmberg et al. (1986)</a> reported a Swedish family in which 8 members had a variant of VWD type 2B, referred to as 'type 2 Malmo.' There was a mild bleeding disorder, and laboratory studies showed that platelets aggregated at much lower ristocetin concentrations than normal. The bleeding time was variously prolonged, and VWF:Ag, VWF activity, and F8 were decreased. All VWF multimers were present, and there was no thrombocytopenia. The defect in this family, inherited as an autosomal dominant, resembled that of type 2B because of the response to ristocetin, but differed because all VWF multimers were present. <a href="#58" class="mim-tip-reference" title="Weiss, J. G., Sussman, I. I. <strong>A new von Willebrand variant (type I, New York): increased ristocetin-induced platelet aggregation and plasma von Willebrand factor containing the full range of multimers.</strong> Blood 68: 149-156, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3487353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3487353</a>]" pmid="3487353">Weiss and Sussman (1986)</a> reported a similarly affected family, and referred to this variant as 'type I New York' (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="#59" class="mim-tip-reference" title="Wylie, B., Gibson, J., Uhr, E., Kronenberg, H. <strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong> Pathology 20: 62-63, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259690</a>] [<a href="https://doi.org/10.3109/00313028809085199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3259690">Wylie et al. (1988)</a> also described this variant and noted that there was no spontaneous aggregation of platelets. <a href="#16" class="mim-tip-reference" title="Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M. <strong>Von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong> J. Clin. Invest. 91: 2169-2177, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486782</a>] [<a href="https://doi.org/10.1172/JCI116443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8486782">Holmberg et al. (1993)</a> reviewed the family reported by <a href="#15" class="mim-tip-reference" title="Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M. <strong>Von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong> Blood 68: 668-672, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>]" pmid="3488775">Holmberg et al. (1986)</a> and reported another affected German family. Affected individuals had only mild bleeding. <a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> emphasized that the variant reported by <a href="#59" class="mim-tip-reference" title="Wylie, B., Gibson, J., Uhr, E., Kronenberg, H. <strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong> Pathology 20: 62-63, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259690</a>] [<a href="https://doi.org/10.3109/00313028809085199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3259690">Wylie et al. (1988)</a> and others was a form of VWD type 2B, with increased sensitivity to ristocetin in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3487353+8486782+16889557+3259690+3488775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Donner, M., Holmberg, L., Nilsson, I. M. <strong>Type IIB von Willebrand's disease with probable autosomal recessive inheritance and presenting as thrombocytopenia in infancy.</strong> Brit. J. Haemat. 66: 349-354, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3497666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3497666</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1987.tb06922.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3497666">Donner et al. (1987)</a> described 2 families with an apparently autosomal recessive form of type 2B von Willebrand disease. The patients presented in infancy with thrombocytopenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3497666" 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="#36" class="mim-tip-reference" title="Murray, E. W., Giles, A. R., Bridge, P. J., Peake, I. R., Lillicrap, D. P. <strong>Cosegregation of von Willebrand factor gene polymorphisms and possible germinal mosaicism in type IIB von Willebrand disease.</strong> Blood 77: 1476-1483, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2009368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2009368</a>]" pmid="2009368">Murray et al. (1991)</a> found evidence of gonadal mosaicism in the father of 2 sibs with VWD type 2B who had inherited the same VWF gene, as marked by polymorphisms, i.e., haplotype, as did 7 unaffected sibs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2009368" 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="Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C. <strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong> Blood 113: 3348-3351, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19060241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19060241</a>] [<a href="https://doi.org/10.1182/blood-2008-06-165233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19060241">Jackson et al. (2009)</a> identified a heterozygous V1316M substitution (<a href="/entry/613160#0007">613160.0007</a>) in affected members of a large French Canadian family with VWD type 2B that had been described originally by <a href="#22" class="mim-tip-reference" title="Lacombe, M., D'Angelo, G. <strong>Etudes sur une thrombopathie familiale.</strong> Nouv. Rev. Franc. Hemat. 3: 611-614, 1963.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14091541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14091541</a>]" pmid="14091541">Lacombe and D'Angelo (1963)</a>; <a href="#33" class="mim-tip-reference" title="Milton, J. G., Frojmovic, M. M. <strong>Shape-changing agents produce abnormally large platelets in a hereditary 'giant platelets syndrome (MPS)'.</strong> J. Lab. Clin. Med. 93: 154-161, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/759524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">759524</a>]" pmid="759524">Milton and Frojmovic (1979)</a>, and <a href="#32" class="mim-tip-reference" title="Milton, J. G., Frojmovic, M. M., Tang, S. S., White, J. G. <strong>Spontaneous platelet aggregation in a hereditary giant platelet syndrome (MPS).</strong> Am. J. Path. 114: 336-345, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6696046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6696046</a>]" pmid="6696046">Milton et al. (1984)</a> referred to the disorder in the family as 'Montreal platelet syndrome.' Affected individuals had lifelong bruising; some patients had severe postoperative bleeding, postpartum hemorrhage, and gastrointestinal bleeding. A significant proportion of platelets occurred in microaggregates typically containing 2 to 6 platelets, and the aggregation could be increased by stirring. <a href="#33" class="mim-tip-reference" title="Milton, J. G., Frojmovic, M. M. <strong>Shape-changing agents produce abnormally large platelets in a hereditary 'giant platelets syndrome (MPS)'.</strong> J. Lab. Clin. Med. 93: 154-161, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/759524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">759524</a>]" pmid="759524">Milton and Frojmovic (1979)</a> suggested that the appearance of abnormally large platelets was related to a defect in the mechanism that regulates platelet size and shape during shape change. <a href="#19" class="mim-tip-reference" title="Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C. <strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong> Blood 113: 3348-3351, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19060241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19060241</a>] [<a href="https://doi.org/10.1182/blood-2008-06-165233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19060241">Jackson et al. (2009)</a> found that affected family members had macrothrombocytopenia, borderline to normal VWF antigen, low ristocetin cofactor activity, and normal factor VIII coagulant activity, all consistent with VWD type 2B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14091541+19060241+759524+6696046" 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>Von Willebrand Disease Type 2M</em></strong></p><p>
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The mutant VWF protein in VWD type 2M shows decreased platelet adhesion without a deficiency of high molecular weight multimers. This functional defect is caused by mutations that disrupt VWF binding to platelets or to subendothelium, consistent with a loss of function (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" 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="#52" class="mim-tip-reference" title="Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D. <strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong> Brit. J. Haemat. 120: 643-651, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588351</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2003.04168.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12588351">Stepanian et al. (2003)</a> reported a French mother and son with VWD type 2M. Both patients had a moderate bleeding syndrome with epistaxis and easy bruising. Laboratory studies showed mildly decreased VWF antigen levels, normal multimers, and severely decreased VWF functional activity. Factor VIII was mildly decreased and platelet counts were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588351" 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>Von Willebrand Disease Type 2N</em></strong></p><p>
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The mutant VWF protein in VWD type 2N shows markedly decreased binding affinity for factor VIII, and this may be confused with mild hemophilia A (<a href="/entry/306700">306700</a>) (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). The phenotype is characterized by a disproportionate decrease in F8 compared to VWF:Ag. VWD type 2N usually shows autosomal recessive inheritance (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="#8" class="mim-tip-reference" title="Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C. <strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong> Blood 77: 1937-1941, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2018834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2018834</a>]" pmid="2018834">Gaucher et al. (1991)</a> noted that the phenotype resembled hemophilia A, or F8 deficiency, but showed autosomal recessive instead of X-linked inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2018834+16889557" 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="#28" class="mim-tip-reference" title="Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M. <strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong> Blood 75: 20-26, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104761</a>]" pmid="2104761">Mazurier et al. (1990)</a> reported a 50-year-old French woman, born of consanguineous parents, with VWD type 2N (previously designated the 'Normandy' variant). She had a lifelong history of excessive bleeding, and laboratory data showed decreased factor VIII, subnormal bleeding time, and normal VWF multimers. VWF isolated from patient plasma was unable to bind factor VIII. <a href="#26" class="mim-tip-reference" title="Lopez-Fernandez, M. F., Blanco-Lopez, M. J., Castineira, M. P., Batlle, J. <strong>Further evidence for recessive inheritance of von Willebrand disease with abnormal binding of von Willebrand factor to factor VIII.</strong> Am. J. Hemat. 40: 20-27, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1566742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1566742</a>] [<a href="https://doi.org/10.1002/ajh.2830400105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1566742">Lopez-Fernandez et al. (1992)</a> described a brother and sister with VWD characterized by abnormal binding of von Willebrand factor to factor VIII. They were presumably homozygous for a recessive VWF defect. <a href="#14" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> reported 2 unrelated French patients with VWD type 2N. Both were adults with lifelong histories of mucocutaneous bleeding and menorrhagia. Laboratory studies showed a dramatic decrease in VWF F8-binding capacity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15461624+2104761+1566742" 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>Von Willebrand Disease Type 2CB</em></strong></p><p>
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<a href="#41" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> proposed a new subtype of VWF characterized by clinically significant bleeding episodes due to a mutant VWF protein with defective collagen binding, termed 'VWF 2CB.' Laboratory studies showed normal values of VWF:RCo to VWF:Ag (RCo:Ag), normal VWF multimer analysis, and normal ristocetin-induced platelet aggregation, but markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) against type III collagen and type I collagen. <a href="#41" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> concluded that the defect was distinct from VWF type 2M, in that type 2M is also characterized by impaired binding to platelet GP1BA and can show a full range of associated VWF multimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" 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>An association between aortic stenosis and hemorrhage from gastrointestinal angiodysplasia has long been recognized. Remarkably, aortic valve replacement, rather than bowel resection, corrects the bleeding. <a href="#56" class="mim-tip-reference" title="Warkentin, T. E., Moore, J. C., Morgan, D. G. <strong>Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link?</strong> Lancet 340: 35-37, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1351610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1351610</a>] [<a href="https://doi.org/10.1016/0140-6736(92)92434-h" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1351610">Warkentin et al. (1992)</a> pointed out that aortic stenosis can be complicated by acquired von Willebrand disease type 2A which is corrected by valve replacement, and hypothesized that acquired VWD was the link. They suggested that in patients with aortic stenosis there is an accelerated clearance of the largest VWF multimers as a result of accelerated platelet/VWF interactions in blood flowing through the stenotic aortic valve. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1351610" 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="#2" class="mim-tip-reference" title="Chey, W. D., Hasler, W. L., Bockenstedt, P. L. <strong>Angiodysplasia and von Willebrand's disease type IIB treated with estrogen/progesterone therapy.</strong> Am. J. Hemat. 41: 276-279, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1288289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1288289</a>] [<a href="https://doi.org/10.1002/ajh.2830410410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1288289">Chey et al. (1992)</a> described gastric angiodysplasia in association with type 2B VWD. Endoscopic electrocautery performed acutely and followed by long-term estrogen/progesterone therapy was accompanied by no recurrence of bleeding during 11 months of follow-up. <a href="#23" class="mim-tip-reference" title="Lavabre-Bertrand, T., Navarro, M., Blanc, P., Larrey, D., Michel, H., Rouanet, C. <strong>Von Willebrand's disease, digestive angiodysplasia, and estrogen-progesterone treatment. (Letter)</strong> Am. J. Hemat. 46: 254-255, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8192164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8192164</a>] [<a href="https://doi.org/10.1002/ajh.2830460325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8192164">Lavabre-Bertrand et al. (1994)</a> corroborated the usefulness of estrogen-progesterone therapy for the bleeding of digestive angiodysplasia on the basis of observations in a 59-year-old man with VWD and life-threatening digestive bleeding. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8192164+1288289" 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>Von Willebrand disease is often treated with the vasopressin analog desmopressin acetate (1-desamino-8-D-arginine vasopressin; dDAVP), which raises the level of factor VIII/von Willebrand factor in plasma. <a href="#17" class="mim-tip-reference" title="Holmberg, L., Nilsson, I. M., Borge, L., Gunnarsson, M., Sjorin, E. <strong>Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in type IIB von Willebrand's disease.</strong> New Eng. J. Med. 309: 816-821, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6412139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6412139</a>] [<a href="https://doi.org/10.1056/NEJM198310063091402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6412139">Holmberg et al. (1983)</a> showed that dDAVP is contraindicated in type 2B VWD because it produces thrombocytopenia in such patients by release of an abnormal factor VIII/von Willebrand factor with platelet-aggregating properties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6412139" 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="#13" class="mim-tip-reference" title="Hall, J. D., Willis, D. W., Evatt, B. L., Jackson, D. W. <strong>Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.</strong> Thromb. Haemost. 57: 332-336, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3116703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3116703</a>]" pmid="3116703">Hall et al. (1987)</a> described 3 monoclonal antibodies produced against von Willebrand factor antigen by conventional hybridoma technique. These antibodies inhibited factor VIII ristocetin cofactor activity but did not inhibit factor VIII coagulant activity. <a href="#13" class="mim-tip-reference" title="Hall, J. D., Willis, D. W., Evatt, B. L., Jackson, D. W. <strong>Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.</strong> Thromb. Haemost. 57: 332-336, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3116703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3116703</a>]" pmid="3116703">Hall et al. (1987)</a> found that the antibodies were useful in differentiating types 1 and 2 VWD. Since desmopressin may be ineffective or even contraindicated in treating patients with type 2 VWD, the differentiation is of clinical importance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3116703" 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 a review of VWD type 2N, <a href="#31" class="mim-tip-reference" title="Mazurier, C. <strong>Von Willebrand disease masquerading as haemophilia A.</strong> Thromb. Haemost. 67: 391-396, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631785</a>]" pmid="1631785">Mazurier (1992)</a> stated that the deficiency of factor VIII could be corrected by infusion of a VWF concentrate almost devoid of factor VIII coagulant activity, and that this treatment was more effective than infusion of factor VIII itself. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631785" 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="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> noted that patients with VWF type 2CB, which is characterized by clinically significant bleeding episodes due to a mutant VWF protein with defective collagen binding, show good functional response to treatment with DDAVP. DDAVP causes a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" 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="#55" class="mim-tip-reference" title="Verweij, C. L., Quadt, R., Briet, E., Dubbeldam, K., van Ommen, G. B., Pannekoek, H. <strong>Genetic linkage of two intragenic restriction fragment length polymorphisms with von Willebrand's disease type IIA: evidence for a defect in the von Willebrand factor gene.</strong> J. Clin. Invest. 81: 1116-1121, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2895123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2895123</a>] [<a href="https://doi.org/10.1172/JCI113425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2895123">Verweij et al. (1988)</a> used RFLPs to demonstrate that the mutation in von Willebrand disease type 2A is in the gene for von Willebrand factor on chromosome 12p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2895123" 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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Mutations causing the enhanced proteolysis phenotype lie within or near domain A2 (exon 28) of the VWF gene, which is the site of the ADAMTS13 (<a href="/entry/604134">604134</a>) cleavage sequence between residues tyr1605 and met1606. Mutations interfering with multimerization occur in regions involved in dimer or multimer assembly, such as the VWF propeptide, the N-terminal D3 domain, the A2 domain, and the C terminus (<a href="#20" class="mim-tip-reference" title="James, P., Lillicrap, D. <strong>The role of molecular genetics in diagnosing von Willebrand disease.</strong> Semin. Thromb. Hemost. 34: 502-508, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19085649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19085649</a>] [<a href="https://doi.org/10.1055/s-0028-1103361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19085649">James and Lillicrap, 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19085649" 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 affected members of a family with von Willebrand disease type 2A, <a href="#18" class="mim-tip-reference" title="Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D. <strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong> Am. J. Hum. Genet. 48: 757-763, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673047</a>]" pmid="1673047">Iannuzzi et al. (1991)</a> identified a 4883T-C heterozygous mutation in the VWF (I865T; <a href="/entry/613160#0001">613160.0001</a>). The I865R substitution was located immediately adjacent to 2 other previously identified mutations that also result in type 2A von Willebrand disease (R834W, <a href="/entry/613160#0002">613160.0002</a> and V844D, <a href="/entry/613160#0003">613160.0003</a>; <a href="#9" class="mim-tip-reference" title="Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y. <strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong> Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786201</a>] [<a href="https://doi.org/10.1073/pnas.86.10.3723" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2786201">Ginsburg et al., 1989</a>), suggesting a clustering for these mutations in a portion of the protein critical for proteolysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1673047+2786201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Dent, J. A., Berkowitz, S. D., Ware, J., Kasper, C. K., Ruggeri, Z. M. <strong>Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.</strong> Proc. Nat. Acad. Sci. 87: 6306-6310, 1990. Note: Erratum: Proc. Nat. Acad. Sci. 87: 9508 only, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385594</a>] [<a href="https://doi.org/10.1073/pnas.87.16.6306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2385594">Dent et al. (1990)</a> noted that the I865T, R834W, and V844D mutations are located within a 32-amino acid segment in the midportion of the 2,813-amino acid VWF coding sequence. Type 2A von Willebrand disease is characterized by normal or only moderately decreased levels of von Willebrand factor, the absence of large and intermediate VWF multimers, and increased VWF proteolysis with an increase in the plasma levels of the 176-kD VWF proteolytic fragment. The ADAMTS13 (<a href="/entry/604134">604134</a>) proteolytic-cleavage site is located between tyr842 and met843 (numbering based on the mature protein). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2385594" 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>Von Willebrand Disease Type 2A/IIE</em></strong></p><p>
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<a href="#50" class="mim-tip-reference" title="Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U. <strong>:A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong> Blood 115: 4894-4901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>] [<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20351307">Schneppenheim et al. (2010)</a> reported a high frequency (29%) of VWD type 2A subtype IIE among patients with type 2A studied in their laboratory. Type IIE is associated with a reduction of high molecular weight (HMW) VWF multimers and a lack of outer proteolytic bands on gel electrophoresis, indicating reduced proteolysis. Genetic analysis of 38 such index cases identified 22 different mutations in the VWF gene, most of them affecting cysteine residues clustered in the D3 domain. The most common mutation was Y1146C (<a href="/entry/613160#0039">613160.0039</a>), which was found in 12 (32%) probands. In vitro expression studies indicated that the Y1146C-mutant protein caused a severe reduction in or lack of HMW monomers and decreased secreted VWF antigen levels. However, clinical symptoms were heterogeneous among carriers, ranging from mild to severe bleeding. <a href="#50" class="mim-tip-reference" title="Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U. <strong>:A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong> Blood 115: 4894-4901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>] [<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20351307">Schneppenheim et al. (2010)</a> suggested that several mechanisms likely act in concert to produce subtype IIE, including decreased secretion of VWF, the change of a cysteine residue which may impact multimerization, and decreased half-life of the mutant protein. Altered ADAMTS13-mediated proteolysis did not appear to be a major primary factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20351307" 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>Von Willebrand Disease Type 2B</em></strong></p><p>
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Mutations causing VWD type 2B tend to cluster within or near the A1 domain of the VWF gene, which mediates platelet GP1BA (<a href="/entry/606672">606672</a>) binding. The mutations appear to enhance platelet binding of VWF by stabilizing the bound conformation (<a href="#47" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" 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 patients with VWD type 2B, <a href="#39" class="mim-tip-reference" title="Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E. <strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong> J. Clin. Invest. 87: 1220-1226, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>] [<a href="https://doi.org/10.1172/JCI115122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2010538">Randi et al. (1991)</a> identified 3 different heterozygous mutations in exon 28 of the VWF gene (<a href="/entry/613160#0005">613160.0005</a>-<a href="/entry/613160#0007">613160.0007</a>) within the domain that interacts with platelet glycoprotein GP1BA, resulting in a loss of function. Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. The region of VWF that binds to GP1BA has been localized to a peptide including amino acids 480 to 718 of the mature subunit that is encoded by exon 28. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2010538" 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 affected members of a Swedish family (<a href="#15" class="mim-tip-reference" title="Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M. <strong>Von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong> Blood 68: 668-672, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>]" pmid="3488775">Holmberg et al., 1986</a>) and a German family with a variant of VWD type 2B, <a href="#16" class="mim-tip-reference" title="Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M. <strong>Von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong> J. Clin. Invest. 91: 2169-2177, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486782</a>] [<a href="https://doi.org/10.1172/JCI116443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8486782">Holmberg et al. (1993)</a> identified a heterozygous mutation in the VWF gene (P1266L; <a href="/entry/613160#0033">613160.0033</a>). The phenotype was unique in that there was a mild bleeding disorder, and laboratory studies showed that platelets aggregated at much lower ristocetin concentrations than normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8486782+3488775" 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>Von Willebrand Disease Type 2M</em></strong></p><p>
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In a French mother and son with VWD type 2M, <a href="#52" class="mim-tip-reference" title="Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D. <strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong> Brit. J. Haemat. 120: 643-651, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588351</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2003.04168.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12588351">Stepanian et al. (2003)</a> identified a heterozygous mutation in the VWF gene (S1285F; <a href="/entry/613160#0030">613160.0030</a>) that altered the folding of the A1 loop and prevented the correct exposure of VWF binding sites to GP1BA. The findings were consistent with a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588351" 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>Von Willebrand Disease Type 2N</em></strong></p><p>
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Mutations that cause VWD type 2N usually occur in the F8-binding site of VWF, which lies between ser764 and arg1035. However, mutations outside of this region have also been reported (<a href="#14" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" 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 a 50-year-old French woman with VWD type 2N reported by <a href="#28" class="mim-tip-reference" title="Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M. <strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong> Blood 75: 20-26, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104761</a>]" pmid="2104761">Mazurier et al. (1990)</a>, <a href="#8" class="mim-tip-reference" title="Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C. <strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong> Blood 77: 1937-1941, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2018834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2018834</a>]" pmid="2018834">Gaucher et al. (1991)</a> identified a homozygous mutation in the VWF gene (T28M in the mature subunit; <a href="/entry/613160#0011">613160.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2018834+2104761" 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="#30" class="mim-tip-reference" title="Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J. <strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong> Brit. J. Haemat. 119: 390-392, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12406074">Mazurier et al. (2002)</a> reported a 20-year-old French woman with VWD type 2N who was compound heterozygosity for 2 mutations in the VWF gene (Y357X, <a href="/entry/613160#0035">613160.0035</a> and C1060R, <a href="/entry/613160#0036">613160.0036</a>). She had very low levels of VWF and F8, and absent binding of VWF to F8. Clinical features included epistaxis, hematomas, and hematemesis throughout childhood. The diagnosis was complicated at first because 2 male first cousins had F8 deficiency (<a href="/entry/306700">306700</a>) due to a hemizygous mutation in the F8 gene (C179G; <a href="/entry/300841#0268">300841.0268</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" 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="#14" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> reported 2 unrelated French patients with type 2N VWD who were compound heterozygous for R854Q (<a href="/entry/613160#0013">613160.0013</a>) and another pathogenic mutation (Y795C, <a href="/entry/613160#0031">613160.0031</a> and C804F, <a href="/entry/613160#0032">613160.0032</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" 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>Von Willebrand Disease Type 2CB</em></strong></p><p>
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In affected members of 2 unrelated families with von Willebrand disease type 2CB, <a href="#41" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> identified heterozygous mutations in the collagen-binding A3 domain of the VWF gene (W1745C; <a href="/entry/613160#0040">613160.0040</a> and S1783A; <a href="/entry/613160#0042">613160.0042</a>, respectively). The authors noted that VWD type 2M is associated with mutations in the A1 domain of VWF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" 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="#40" class="mim-tip-reference" title="Rayes, J., Hollestelle, M. J., Legendre, P., Marx, I., de Groot, P. G., Christophe, O. D., Lenting, P. J., Denis, C. V. <strong>Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B.</strong> Blood 115: 4870-4877, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20200350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20200350</a>] [<a href="https://doi.org/10.1182/blood-2009-11-254193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20200350">Rayes et al. (2010)</a> and <a href="#10" class="mim-tip-reference" title="Golder, M., Pruss, C. M., Hegadorn, C., Mewburn, J., Laverty, K., Sponagle, K., Lillicrap, D. <strong>Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.</strong> Blood 115: 4862-4869, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20371742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20371742</a>] [<a href="https://doi.org/10.1182/blood-2009-11-253120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20371742">Golder et al. (2010)</a> independently developed mouse models of VWD type 2B that recapitulated the human phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20371742+20200350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Asakura1987" class="mim-tip-reference" title="Asakura, A., Harrison, J., Gomperts, E., Abildgaard, C. <strong>Type IIA von Willebrand disease with apparent recessive inheritance.</strong> Blood 69: 1419-1420, 1987.">Asakura et al. (1987)</a>; <a href="#Cooney1991" class="mim-tip-reference" title="Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D. <strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong> J. Clin. Invest. 87: 1227-1233, 1991.">Cooney et al. (1991)</a>; <a href="#Donner1991" class="mim-tip-reference" title="Donner, M., Andersson, A.-M., Kristoffersson, A.-C., Nilsson, I. M., Dahlback, B., Holmberg, L. <strong>An arg545-to-cys substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease.</strong> Europ. J. Haemat. 47: 342-345, 1991.">Donner et al. (1991)</a>; <a href="#Donner1992" class="mim-tip-reference" title="Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L. <strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong> Brit. J. Haemat. 82: 58-65, 1992.">Donner et al. (1992)</a>; <a href="#Kyrle1988" class="mim-tip-reference" title="Kyrle, P. A., Niessner, H., Dent, J., Panzer, S., Brenner, B., Zimmerman, T. S., Lechner, K. <strong>IIB von Willebrand's disease: pathogenetic and therapeutic studies.</strong> Brit. J. Haemat. 69: 55-59, 1988.">Kyrle et al. (1988)</a>; <a href="#Lavergne1992" class="mim-tip-reference" title="Lavergne, J.-M., De Paillette, L., Bahnak, B. R., Ribba, A.-S., Fressinaud, E., Meyer, D., Pietu, G. <strong>Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.</strong> Brit. J. Haemat. 82: 66-72, 1992.">Lavergne et al. (1992)</a>; <a href="#Mazurier1990" class="mim-tip-reference" title="Mazurier, C., Gaucher, C., Jorieux, S., Parquet-Gernez, A., Goudemand, M. <strong>Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.</strong> Brit. J. Haemat. 76: 372-379, 1990.">Mazurier et al. (1990)</a>; <a href="#Montgomery1982" class="mim-tip-reference" title="Montgomery, R. R., Hathaway, W. E., Johnson, J., Jacobson, L., Muntean, W. <strong>A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity.</strong> Blood 60: 201-207, 1982.">Montgomery et al. (1982)</a>; <a href="#Montgomery1978" class="mim-tip-reference" title="Montgomery, R. R., Zimmerman, T. S. <strong>Von Willebrand's disease antigen II: a new plasma and platelet antigen deficient in severe von Willebrand's disease.</strong> J. Clin. Invest. 61: 1498-1507, 1978.">Montgomery and
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Zimmerman (1978)</a>; <a href="#Murray1992" class="mim-tip-reference" title="Murray, E. W., Giles, A. R., Lillicrap, D. <strong>Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease.</strong> Am. J. Hum. Genet. 50: 199-207, 1992.">Murray et al. (1992)</a>; <a href="#Ruggeri1982" class="mim-tip-reference" title="Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S. <strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong> J. Clin. Invest. 70: 1124-1127, 1982.">Ruggeri et al. (1982)</a>; <a href="#Ruggeri1982" class="mim-tip-reference" title="Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S. <strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong> J. Clin. Invest. 70: 1124-1127, 1982.">Ruggeri et al. (1982)</a>; <a href="#Ruggeri1980" class="mim-tip-reference" title="Ruggeri, Z. M., Zimmerman, T. S. <strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong> J. Clin. Invest. 65: 1318-1325, 1980.">Ruggeri et al. (1980)</a>; <a href="#Ruggeri1980" class="mim-tip-reference" title="Ruggeri, Z. M., Zimmerman, T. S. <strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong> J. Clin. Invest. 65: 1318-1325, 1980.">Ruggeri and Zimmerman
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(1980)</a>; <a href="#Schneppenheim1996" class="mim-tip-reference" title="Schneppenheim, R., Brassard, J., Krey, S., Budde, U., Kunicki, T. J., Holmberg, L., Ware, J., Ruggeri, Z. M. <strong>Defective dimerization of von Willebrand factor subunits due to a cys-to-arg mutation in type IID von Willebrand disease.</strong> Proc. Nat. Acad. Sci. 93: 3581-3586, 1996.">Schneppenheim et al. (1996)</a>; <a href="#Schneppenheim2000" class="mim-tip-reference" title="Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R. <strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong> Thromb. Haemost. 83: 136-140, 2000.">Schneppenheim et al. (2000)</a>; <a href="#Schneppenheim1995" class="mim-tip-reference" title="Schneppenheim, R., Thomas, K. B., Krey, S., Budde, U., Jessat, U., Sutor, A. H., Zieger, B. <strong>Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.</strong> Hum. Genet. 95: 681-686, 1995.">Schneppenheim et al. (1995)</a>; <a href="#Takahashi1980" class="mim-tip-reference" title="Takahashi, H., Sakuragawa, N., Shibata, A. <strong>Von Willebrand disease with an increased ristocetin-induced platelet aggregation and a qualitative abnormality of the factor VIII protein.</strong> Am. J. Hemat. 8: 299-308, 1980.">Takahashi et al. (1980)</a>; <a href="#Tuley1991" class="mim-tip-reference" title="Tuley, E. A., Gaucher, C., Jorieux, S., Worrall, N. K., Sadler, J. E., Mazurier, C. <strong>Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A.</strong> Proc. Nat. Acad. Sci. 88: 6377-6381, 1991.">Tuley et al.
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(1991)</a>; <a href="#Weinger1981" class="mim-tip-reference" title="Weinger, R. S., Cimo, P. L., Moake, J. L., Olson, J. D., Heller, M. S. <strong>Type IIB von Willebrand's disease: unusual response to cryoprecipitate infusion.</strong> Ann. Intern. Med. 94: 47-50, 1981.">Weinger et al. (1981)</a>; <a href="#Zieger1997" class="mim-tip-reference" title="Zieger, B., Budde, U., Jessat, U., Zimmermann, R., Simon, M., Katzel, R., Sutor, A. H. <strong>New families with von Willebrand disease type 2M (Vicenza).</strong> Thromb. Res. 87: 57-64, 1997.">Zieger et al. (1997)</a>
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Asakura, A., Harrison, J., Gomperts, E., Abildgaard, C.
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<strong>Type IIA von Willebrand disease with apparent recessive inheritance.</strong>
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Blood 69: 1419-1420, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3105622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3105622</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3105622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Chey, W. D., Hasler, W. L., Bockenstedt, P. L.
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<strong>Angiodysplasia and von Willebrand's disease type IIB treated with estrogen/progesterone therapy.</strong>
|
|
Am. J. Hemat. 41: 276-279, 1992.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1288289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1288289</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1288289" 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/ajh.2830410410" target="_blank">Full Text</a>]
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<a id="Cooney1991" class="mim-anchor"></a>
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Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D.
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<strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong>
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J. Clin. Invest. 87: 1227-1233, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672694</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1672694" 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/10.1172/JCI115123" target="_blank">Full Text</a>]
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Dent, J. A., Berkowitz, S. D., Ware, J., Kasper, C. K., Ruggeri, Z. M.
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<strong>Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 6306-6310, 1990. Note: Erratum: Proc. Nat. Acad. Sci. 87: 9508 only, 1990.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2385594" 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/10.1073/pnas.87.16.6306" target="_blank">Full Text</a>]
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Donner, M., Andersson, A.-M., Kristoffersson, A.-C., Nilsson, I. M., Dahlback, B., Holmberg, L.
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<strong>An arg545-to-cys substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease.</strong>
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Europ. J. Haemat. 47: 342-345, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1761120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1761120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1761120" 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/10.1111/j.1600-0609.1991.tb01858.x" target="_blank">Full Text</a>]
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Donner, M., Holmberg, L., Nilsson, I. M.
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<strong>Type IIB von Willebrand's disease with probable autosomal recessive inheritance and presenting as thrombocytopenia in infancy.</strong>
|
|
Brit. J. Haemat. 66: 349-354, 1987.
|
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3497666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3497666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3497666" 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/10.1111/j.1365-2141.1987.tb06922.x" target="_blank">Full Text</a>]
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Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L.
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<strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong>
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Brit. J. Haemat. 82: 58-65, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419803</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419803" 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/10.1111/j.1365-2141.1992.tb04594.x" target="_blank">Full Text</a>]
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Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C.
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<strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong>
|
|
Blood 77: 1937-1941, 1991.
|
|
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|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2018834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2018834</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2018834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y.
|
|
<strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2786201" 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/10.1073/pnas.86.10.3723" target="_blank">Full Text</a>]
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Golder, M., Pruss, C. M., Hegadorn, C., Mewburn, J., Laverty, K., Sponagle, K., Lillicrap, D.
|
|
<strong>Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.</strong>
|
|
Blood 115: 4862-4869, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20371742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20371742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20371742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-11-253120" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Goodeve2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goodeve, A. C.
|
|
<strong>The genetic basis of von Willebrand disease.</strong>
|
|
Blood Rev. 24: 123-134, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Gralnick1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gralnick, H. R., Williams, S. B., McKeown, L. P., Rick, M. E., Maisonneuve, P., Jenneau, C., Sultan, Y.
|
|
<strong>Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.</strong>
|
|
J. Clin. Invest. 76: 1522-1529, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2932469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2932469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2932469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112132" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hall1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, J. D., Willis, D. W., Evatt, B. L., Jackson, D. W.
|
|
<strong>Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.</strong>
|
|
Thromb. Haemost. 57: 332-336, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3116703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3116703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3116703" 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="14" class="mim-anchor"></a>
|
|
<a id="Hilbert2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease.
|
|
<strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong>
|
|
Brit. J. Haemat. 127: 184-189, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" 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.1365-2141.2004.05187.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Holmberg1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M.
|
|
<strong>Von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong>
|
|
Blood 68: 668-672, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3488775" 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="Holmberg1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M.
|
|
<strong>Von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong>
|
|
J. Clin. Invest. 91: 2169-2177, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8486782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI116443" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Holmberg1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Nilsson, I. M., Borge, L., Gunnarsson, M., Sjorin, E.
|
|
<strong>Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in type IIB von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 309: 816-821, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6412139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6412139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6412139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198310063091402" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Iannuzzi1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D.
|
|
<strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong>
|
|
Am. J. Hum. Genet. 48: 757-763, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Jackson2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C.
|
|
<strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong>
|
|
Blood 113: 3348-3351, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19060241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19060241</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19060241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-06-165233" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="James2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
James, P., Lillicrap, D.
|
|
<strong>The role of molecular genetics in diagnosing von Willebrand disease.</strong>
|
|
Semin. Thromb. Hemost. 34: 502-508, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19085649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19085649</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19085649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1055/s-0028-1103361" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Kyrle1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kyrle, P. A., Niessner, H., Dent, J., Panzer, S., Brenner, B., Zimmerman, T. S., Lechner, K.
|
|
<strong>IIB von Willebrand's disease: pathogenetic and therapeutic studies.</strong>
|
|
Brit. J. Haemat. 69: 55-59, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3132965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3132965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3132965" 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.1365-2141.1988.tb07602.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lacombe1963" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lacombe, M., D'Angelo, G.
|
|
<strong>Etudes sur une thrombopathie familiale.</strong>
|
|
Nouv. Rev. Franc. Hemat. 3: 611-614, 1963.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14091541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14091541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14091541" 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="23" class="mim-anchor"></a>
|
|
<a id="Lavabre-Bertrand1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lavabre-Bertrand, T., Navarro, M., Blanc, P., Larrey, D., Michel, H., Rouanet, C.
|
|
<strong>Von Willebrand's disease, digestive angiodysplasia, and estrogen-progesterone treatment. (Letter)</strong>
|
|
Am. J. Hemat. 46: 254-255, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8192164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8192164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8192164" 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/ajh.2830460325" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Lavergne1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lavergne, J.-M., De Paillette, L., Bahnak, B. R., Ribba, A.-S., Fressinaud, E., Meyer, D., Pietu, G.
|
|
<strong>Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.</strong>
|
|
Brit. J. Haemat. 82: 66-72, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419804" 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.1365-2141.1992.tb04595.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Lillicrap2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lillicrap, D.
|
|
<strong>Genotype/phenotype association in von Willebrand disease: is the glass half full or empty?</strong>
|
|
J. Thromb. Haemost. 7 (suppl. 1): 65-70, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19630771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19630771</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19630771" 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.1538-7836.2009.03367.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Lopez-Fernandez1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lopez-Fernandez, M. F., Blanco-Lopez, M. J., Castineira, M. P., Batlle, J.
|
|
<strong>Further evidence for recessive inheritance of von Willebrand disease with abnormal binding of von Willebrand factor to factor VIII.</strong>
|
|
Am. J. Hemat. 40: 20-27, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1566742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1566742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1566742" 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/ajh.2830400105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Mannucci2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mannucci, P. M.
|
|
<strong>Treatment of von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 351: 683-694, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15306670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15306670</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15306670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMra040403" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Mazurier1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M.
|
|
<strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong>
|
|
Blood 75: 20-26, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104761" 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="29" class="mim-anchor"></a>
|
|
<a id="Mazurier1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Gaucher, C., Jorieux, S., Parquet-Gernez, A., Goudemand, M.
|
|
<strong>Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.</strong>
|
|
Brit. J. Haemat. 76: 372-379, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2124499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2124499</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2124499" 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.1365-2141.1990.tb06371.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Mazurier2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J.
|
|
<strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong>
|
|
Brit. J. Haemat. 119: 390-392, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Mazurier1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C.
|
|
<strong>Von Willebrand disease masquerading as haemophilia A.</strong>
|
|
Thromb. Haemost. 67: 391-396, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631785" 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="32" class="mim-anchor"></a>
|
|
<a id="Milton1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Milton, J. G., Frojmovic, M. M., Tang, S. S., White, J. G.
|
|
<strong>Spontaneous platelet aggregation in a hereditary giant platelet syndrome (MPS).</strong>
|
|
Am. J. Path. 114: 336-345, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6696046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6696046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6696046" 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="33" class="mim-anchor"></a>
|
|
<a id="Milton1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Milton, J. G., Frojmovic, M. M.
|
|
<strong>Shape-changing agents produce abnormally large platelets in a hereditary 'giant platelets syndrome (MPS)'.</strong>
|
|
J. Lab. Clin. Med. 93: 154-161, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/759524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">759524</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=759524" 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="34" class="mim-anchor"></a>
|
|
<a id="Montgomery1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montgomery, R. R., Hathaway, W. E., Johnson, J., Jacobson, L., Muntean, W.
|
|
<strong>A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity.</strong>
|
|
Blood 60: 201-207, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6805535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6805535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6805535" 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="Montgomery1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montgomery, R. R., Zimmerman, T. S.
|
|
<strong>Von Willebrand's disease antigen II: a new plasma and platelet antigen deficient in severe von Willebrand's disease.</strong>
|
|
J. Clin. Invest. 61: 1498-1507, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/307007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">307007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=307007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI109070" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Murray1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murray, E. W., Giles, A. R., Bridge, P. J., Peake, I. R., Lillicrap, D. P.
|
|
<strong>Cosegregation of von Willebrand factor gene polymorphisms and possible germinal mosaicism in type IIB von Willebrand disease.</strong>
|
|
Blood 77: 1476-1483, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2009368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2009368</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2009368" 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="Murray1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murray, E. W., Giles, A. R., Lillicrap, D.
|
|
<strong>Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease.</strong>
|
|
Am. J. Hum. Genet. 50: 199-207, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1729889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1729889</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1729889" 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="Othman2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Othman, M., Favaloro, E. J.
|
|
<strong>Genetics of type 2B von Willebrand disease: 'true 2B,' 'tricky 2B,' or 'not 2B.' What are the modifiers of the phenotype?</strong>
|
|
Semin. Thromb. Hemost. 34: 520-531, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19085651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19085651</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19085651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1055/s-0028-1103363" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Randi1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E.
|
|
<strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong>
|
|
J. Clin. Invest. 87: 1220-1226, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2010538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115122" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Rayes2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rayes, J., Hollestelle, M. J., Legendre, P., Marx, I., de Groot, P. G., Christophe, O. D., Lenting, P. J., Denis, C. V.
|
|
<strong>Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B.</strong>
|
|
Blood 115: 4870-4877, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20200350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20200350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20200350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-11-254193" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Riddell2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A.
|
|
<strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong>
|
|
Blood 114: 3489-3496, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Ruggeri1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Lombardi, R., Gatti, L., Bader, R., Valsecchi, C., Zimmerman, T. S.
|
|
<strong>Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von Willebrand factor.</strong>
|
|
Blood 60: 1453-1456, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982737" 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="43" class="mim-anchor"></a>
|
|
<a id="Ruggeri1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S.
|
|
<strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong>
|
|
J. Clin. Invest. 70: 1124-1127, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/jci110700" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Ruggeri1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Pareti, F. I., Mannucci, P. M., Ciavarella, N., Zimmerman, T. S.
|
|
<strong>Heightened interaction between platelets and factor VIII von Willebrand factor in a new subtype of von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 302: 1047-1051, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6767976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6767976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6767976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198005083021902" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Ruggeri1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong>
|
|
J. Clin. Invest. 65: 1318-1325, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6773982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6773982</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6773982" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI109795" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Saba1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saba, H. I., Saba, S. R., Dent, J., Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.</strong>
|
|
Blood 66: 282-286, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3926021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3926021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3926021" 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="47" class="mim-anchor"></a>
|
|
<a id="Sadler2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others.
|
|
<strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong>
|
|
J. Thromb. Haemost. 4: 2103-2114, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" 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.1538-7836.2006.02146.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Schneppenheim1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Brassard, J., Krey, S., Budde, U., Kunicki, T. J., Holmberg, L., Ware, J., Ruggeri, Z. M.
|
|
<strong>Defective dimerization of von Willebrand factor subunits due to a cys-to-arg mutation in type IID von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 3581-3586, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8622978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8622978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8622978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.93.8.3581" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Schneppenheim2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R.
|
|
<strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong>
|
|
Thromb. Haemost. 83: 136-140, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10669167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10669167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10669167" 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="50" class="mim-anchor"></a>
|
|
<a id="Schneppenheim2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U.
|
|
<strong>:A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong>
|
|
Blood 115: 4894-4901, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20351307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Schneppenheim1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Thomas, K. B., Krey, S., Budde, U., Jessat, U., Sutor, A. H., Zieger, B.
|
|
<strong>Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.</strong>
|
|
Hum. Genet. 95: 681-686, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00209487" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Stepanian2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D.
|
|
<strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 120: 643-651, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2003.04168.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Takahashi1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takahashi, H., Sakuragawa, N., Shibata, A.
|
|
<strong>Von Willebrand disease with an increased ristocetin-induced platelet aggregation and a qualitative abnormality of the factor VIII protein.</strong>
|
|
Am. J. Hemat. 8: 299-308, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6774612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6774612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6774612" 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/ajh.2830080308" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Tuley1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tuley, E. A., Gaucher, C., Jorieux, S., Worrall, N. K., Sadler, J. E., Mazurier, C.
|
|
<strong>Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 6377-6381, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1906179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1906179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.88.14.6377" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Verweij1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verweij, C. L., Quadt, R., Briet, E., Dubbeldam, K., van Ommen, G. B., Pannekoek, H.
|
|
<strong>Genetic linkage of two intragenic restriction fragment length polymorphisms with von Willebrand's disease type IIA: evidence for a defect in the von Willebrand factor gene.</strong>
|
|
J. Clin. Invest. 81: 1116-1121, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2895123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2895123</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2895123" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI113425" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Warkentin1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Warkentin, T. E., Moore, J. C., Morgan, D. G.
|
|
<strong>Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link?</strong>
|
|
Lancet 340: 35-37, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1351610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1351610</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1351610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0140-6736(92)92434-h" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Weinger1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weinger, R. S., Cimo, P. L., Moake, J. L., Olson, J. D., Heller, M. S.
|
|
<strong>Type IIB von Willebrand's disease: unusual response to cryoprecipitate infusion.</strong>
|
|
Ann. Intern. Med. 94: 47-50, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6778284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6778284</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6778284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-94-1-47" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Weiss1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weiss, J. G., Sussman, I. I.
|
|
<strong>A new von Willebrand variant (type I, New York): increased ristocetin-induced platelet aggregation and plasma von Willebrand factor containing the full range of multimers.</strong>
|
|
Blood 68: 149-156, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3487353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3487353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3487353" 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="59" class="mim-anchor"></a>
|
|
<a id="Wylie1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wylie, B., Gibson, J., Uhr, E., Kronenberg, H.
|
|
<strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong>
|
|
Pathology 20: 62-63, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3259690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3109/00313028809085199" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Zieger1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zieger, B., Budde, U., Jessat, U., Zimmermann, R., Simon, M., Katzel, R., Sutor, A. H.
|
|
<strong>New families with von Willebrand disease type 2M (Vicenza).</strong>
|
|
Thromb. Res. 87: 57-64, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9253800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9253800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9253800" 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/s0049-3848(97)00104-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Zimmerman1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zimmerman, T. S., Dent, J. A., Ruggeri, Z. M., Nannini, L. H.
|
|
<strong>Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE).</strong>
|
|
J. Clin. Invest. 77: 947-951, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485111</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112394" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Zimmerman1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zimmerman, T. S., Ruggeri, Z. M.
|
|
<strong>Von Willebrand disease.</strong>
|
|
Hum. Path. 18: 140-152, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3100416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3100416</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3100416" 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/s0046-8177(87)80332-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
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Cassandra L. Kniffin - updated : 4/29/2013
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Cassandra L. Kniffin - updated : 5/10/2011<br>Cassandra L. Kniffin - updated : 10/8/2010
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Cassandra L. Kniffin : 9/8/2010
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carol : 02/22/2022
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carol : 08/07/2019<br>alopez : 08/06/2019<br>carol : 10/21/2016<br>alopez : 05/03/2013<br>ckniffin : 5/1/2013<br>ckniffin : 4/29/2013<br>terry : 8/9/2012<br>wwang : 6/13/2011<br>ckniffin : 5/10/2011<br>carol : 4/7/2011<br>terry : 1/7/2011<br>terry : 11/24/2010<br>wwang : 11/2/2010<br>ckniffin : 10/8/2010<br>terry : 10/8/2010<br>carol : 10/4/2010<br>ckniffin : 9/29/2010
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<span class="mim-font">
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<strong>#</strong> 613554
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VON WILLEBRAND DISEASE, TYPE 2; VWD2
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<em>Alternative titles; symbols</em>
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VON WILLEBRAND DISEASE, TYPE II<br />
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VWD, TYPE 2
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Other entities represented in this entry:
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VON WILLEBRAND DISEASE, TYPE 2A, INCLUDED; VWD2A, INCLUDED
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VON WILLEBRAND DISEASE, TYPE 2B, INCLUDED; VWD2B, INCLUDED<br />
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VON WILLEBRAND DISEASE, TYPE 2M, INCLUDED; VWD2M, INCLUDED<br />
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VON WILLEBRAND DISEASE, TYPE 2N, INCLUDED; VWD2N, INCLUDED
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<strong>SNOMEDCT:</strong> 128107007, 359711001, 359717002, 359732009;
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<strong>ICD10CM:</strong> D68.02, D68.020, D68.021, D68.022, D68.023, D68.029;
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<strong>ORPHA:</strong> 166081, 166084, 166087, 166090, 166093, 903;
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<strong>DO:</strong> 0060574;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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12p13.31
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von Willebrand disease, types 2A, 2B, 2M, and 2N
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613554
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Autosomal dominant; Autosomal recessive
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<span class="mim-font">
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3
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VWF
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613160
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<p>A number sign (#) is used with this entry because von Willebrand disease (VWD) type 2 is caused by mutation in the gene encoding von Willebrand factor (VWF; 613160), which maps to chromosome 12p13.</p>
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<strong>Description</strong>
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<p>Von Willebrand disease is the most common inherited bleeding disorder. It is characterized clinically by mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. It results from a defect in platelet aggregation due to defects in the von Willebrand factor. Von Willebrand factor is a large, multimeric protein that plays a role in platelet adhesion and also serves as a carrier for the thrombotic protein factor VIII (F8; 300841). F8 is mutated in hemophilia A (306700) (review by Goodeve, 2010). </p><p>Whereas von Willebrand disease types 1 (193400) and 3 (277480) are characterized by quantitative defects in the VWF gene, von Willebrand disease type 2, which is divided in subtypes 2A, 2B, 2M, and 2N, is characterized by qualitative abnormalities of the VWF protein. The mutant VWF protein in types 2A, 2B, and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind F8. VWD2 accounts for 20 to 30% of cases of VWD (Mannucci, 2004; Sadler et al., 2006; Lillicrap, 2009; Goodeve, 2010). </p><p>For a general discussion and a classification of the types of von Willebrand disease, see VWD type 1 (193400).</p>
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<strong>Clinical Features</strong>
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<p>Von Willebrand disease type 2, like VWD type 1, is characterized by excessive mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery (Mannucci, 2004). The delineation of different subtypes of VWD type 2 does not reflect clinical differences, but rather different mutant VWF protein phenotypes, which may affect diagnosis, treatment, and counseling (Sadler et al., 2006). </p>
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<strong>Inheritance</strong>
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<p>Inheritance of VWD type 2 is generally autosomal dominant, although some cases are characterized by autosomal recessive transmission (Mannucci, 2004). </p>
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<strong>Pathogenesis</strong>
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<p><strong><em>Von Willebrand Disease Type 2A</em></strong></p><p>
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The mutant VWF protein in von Willebrand disease type 2A has decreased platelet adhesion due to a selective deficiency of high molecular weight multimers. The decrease in large multimers can be due to (1) a failure to synthesize the multimers ('group 1') or (2) enhanced ADAMTS13 (604134)-mediated proteolysis of the secreted high molecular weight protein ('group 2'). Regardless of mechanism in type 2A, the loss of large multimers is associated with decreased VWF-platelet interactions and/or decreased VWF-connective tissue interactions (reviews by Sadler et al., 2006 and Lillicrap, 2009). </p><p>Historically, type 2A was subclassified into types IIA, IIC, IID, and IIE. The mutant VWF in type IIA showed increased proteolysis by ADAMTS13; type IIC showed impaired multimerization in the Golgi apparatus due to mutation in the VWF propeptide (Zimmerman and Ruggeri, 1987); type IID showed impaired dimerization in the endoplasmic reticulum due to mutations in the C-terminal domain; and type IIE showed impaired intersubunit disulfide bond formation in the Golgi apparatus (Sadler et al., 2006) and a lack of outer proteolytic bands on gel electrophoresis, indicating reduced proteolysis (Zimmerman et al., 1986). All these subtypes showed dominant inheritance except for IIC, which showed recessive inheritance. These subtypes of type 2A are no longer used because the discrimination has not shown clinical utility; all are now referred to as type 2A (Sadler et al., 2006). </p><p>Gralnick et al. (1985) found that in VWD type 2A, inhibition of a calcium-dependent protease in vitro resulted in correction of the abnormal multimeric structure. This suggested that an abnormal VWF protein synthesized in this disorder is susceptible to proteolytic degradation, a process which may play an important role in phenotypic expression of the disease. </p><p><strong><em>Von Willebrand Disease Type 2B</em></strong></p><p>
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The mutant VWF protein in VWD type 2B shows increased affinity to platelet GP1BA (606672), resulting in increased platelet aggregation, and increased proteolysis of VWF subunits causing a decrease of large VWF multimers. Patients often have secondary thrombocytopenia due to platelet consumption (Sadler et al., 2006). </p><p>Othman and Favaloro (2008) reviewed the complexity of VWD type 2B, noting that atypical forms with complete VWF monomers, no mutations in the A1 domain, or with giant platelets have also been reported, suggesting the presence of phenotypic modifiers. </p><p>Saba et al. (1985) found chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro in affected members of a family with VWD type 2B. The 4 affected family members identified were a man and 2 sons and a daughter by 2 different wives. </p><p>Holmberg et al. (1986) reported a Swedish family in which 8 members had a variant of VWD type 2B, referred to as 'type 2 Malmo.' There was a mild bleeding disorder, and laboratory studies showed that platelets aggregated at much lower ristocetin concentrations than normal. The bleeding time was variously prolonged, and VWF:Ag, VWF activity, and F8 were decreased. All VWF multimers were present, and there was no thrombocytopenia. The defect in this family, inherited as an autosomal dominant, resembled that of type 2B because of the response to ristocetin, but differed because all VWF multimers were present. Weiss and Sussman (1986) reported a similarly affected family, and referred to this variant as 'type I New York' (Sadler et al., 2006). Wylie et al. (1988) also described this variant and noted that there was no spontaneous aggregation of platelets. Holmberg et al. (1993) reviewed the family reported by Holmberg et al. (1986) and reported another affected German family. Affected individuals had only mild bleeding. Sadler et al. (2006) emphasized that the variant reported by Wylie et al. (1988) and others was a form of VWD type 2B, with increased sensitivity to ristocetin in vivo. </p><p>Donner et al. (1987) described 2 families with an apparently autosomal recessive form of type 2B von Willebrand disease. The patients presented in infancy with thrombocytopenia. </p><p>Murray et al. (1991) found evidence of gonadal mosaicism in the father of 2 sibs with VWD type 2B who had inherited the same VWF gene, as marked by polymorphisms, i.e., haplotype, as did 7 unaffected sibs. </p><p>Jackson et al. (2009) identified a heterozygous V1316M substitution (613160.0007) in affected members of a large French Canadian family with VWD type 2B that had been described originally by Lacombe and D'Angelo (1963); Milton and Frojmovic (1979), and Milton et al. (1984) referred to the disorder in the family as 'Montreal platelet syndrome.' Affected individuals had lifelong bruising; some patients had severe postoperative bleeding, postpartum hemorrhage, and gastrointestinal bleeding. A significant proportion of platelets occurred in microaggregates typically containing 2 to 6 platelets, and the aggregation could be increased by stirring. Milton and Frojmovic (1979) suggested that the appearance of abnormally large platelets was related to a defect in the mechanism that regulates platelet size and shape during shape change. Jackson et al. (2009) found that affected family members had macrothrombocytopenia, borderline to normal VWF antigen, low ristocetin cofactor activity, and normal factor VIII coagulant activity, all consistent with VWD type 2B. </p><p><strong><em>Von Willebrand Disease Type 2M</em></strong></p><p>
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The mutant VWF protein in VWD type 2M shows decreased platelet adhesion without a deficiency of high molecular weight multimers. This functional defect is caused by mutations that disrupt VWF binding to platelets or to subendothelium, consistent with a loss of function (Sadler et al., 2006). </p><p>Stepanian et al. (2003) reported a French mother and son with VWD type 2M. Both patients had a moderate bleeding syndrome with epistaxis and easy bruising. Laboratory studies showed mildly decreased VWF antigen levels, normal multimers, and severely decreased VWF functional activity. Factor VIII was mildly decreased and platelet counts were normal. </p><p><strong><em>Von Willebrand Disease Type 2N</em></strong></p><p>
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The mutant VWF protein in VWD type 2N shows markedly decreased binding affinity for factor VIII, and this may be confused with mild hemophilia A (306700) (Sadler et al., 2006). The phenotype is characterized by a disproportionate decrease in F8 compared to VWF:Ag. VWD type 2N usually shows autosomal recessive inheritance (Sadler et al., 2006). Gaucher et al. (1991) noted that the phenotype resembled hemophilia A, or F8 deficiency, but showed autosomal recessive instead of X-linked inheritance. </p><p>Mazurier et al. (1990) reported a 50-year-old French woman, born of consanguineous parents, with VWD type 2N (previously designated the 'Normandy' variant). She had a lifelong history of excessive bleeding, and laboratory data showed decreased factor VIII, subnormal bleeding time, and normal VWF multimers. VWF isolated from patient plasma was unable to bind factor VIII. Lopez-Fernandez et al. (1992) described a brother and sister with VWD characterized by abnormal binding of von Willebrand factor to factor VIII. They were presumably homozygous for a recessive VWF defect. Hilbert et al. (2004) reported 2 unrelated French patients with VWD type 2N. Both were adults with lifelong histories of mucocutaneous bleeding and menorrhagia. Laboratory studies showed a dramatic decrease in VWF F8-binding capacity. </p><p><strong><em>Von Willebrand Disease Type 2CB</em></strong></p><p>
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Riddell et al. (2009) proposed a new subtype of VWF characterized by clinically significant bleeding episodes due to a mutant VWF protein with defective collagen binding, termed 'VWF 2CB.' Laboratory studies showed normal values of VWF:RCo to VWF:Ag (RCo:Ag), normal VWF multimer analysis, and normal ristocetin-induced platelet aggregation, but markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) against type III collagen and type I collagen. Riddell et al. (2009) concluded that the defect was distinct from VWF type 2M, in that type 2M is also characterized by impaired binding to platelet GP1BA and can show a full range of associated VWF multimers. </p>
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<strong>Other Features</strong>
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<p>An association between aortic stenosis and hemorrhage from gastrointestinal angiodysplasia has long been recognized. Remarkably, aortic valve replacement, rather than bowel resection, corrects the bleeding. Warkentin et al. (1992) pointed out that aortic stenosis can be complicated by acquired von Willebrand disease type 2A which is corrected by valve replacement, and hypothesized that acquired VWD was the link. They suggested that in patients with aortic stenosis there is an accelerated clearance of the largest VWF multimers as a result of accelerated platelet/VWF interactions in blood flowing through the stenotic aortic valve. </p><p>Chey et al. (1992) described gastric angiodysplasia in association with type 2B VWD. Endoscopic electrocautery performed acutely and followed by long-term estrogen/progesterone therapy was accompanied by no recurrence of bleeding during 11 months of follow-up. Lavabre-Bertrand et al. (1994) corroborated the usefulness of estrogen-progesterone therapy for the bleeding of digestive angiodysplasia on the basis of observations in a 59-year-old man with VWD and life-threatening digestive bleeding. </p>
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<strong>Clinical Management</strong>
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<p>Von Willebrand disease is often treated with the vasopressin analog desmopressin acetate (1-desamino-8-D-arginine vasopressin; dDAVP), which raises the level of factor VIII/von Willebrand factor in plasma. Holmberg et al. (1983) showed that dDAVP is contraindicated in type 2B VWD because it produces thrombocytopenia in such patients by release of an abnormal factor VIII/von Willebrand factor with platelet-aggregating properties. </p><p>Hall et al. (1987) described 3 monoclonal antibodies produced against von Willebrand factor antigen by conventional hybridoma technique. These antibodies inhibited factor VIII ristocetin cofactor activity but did not inhibit factor VIII coagulant activity. Hall et al. (1987) found that the antibodies were useful in differentiating types 1 and 2 VWD. Since desmopressin may be ineffective or even contraindicated in treating patients with type 2 VWD, the differentiation is of clinical importance. </p><p>In a review of VWD type 2N, Mazurier (1992) stated that the deficiency of factor VIII could be corrected by infusion of a VWF concentrate almost devoid of factor VIII coagulant activity, and that this treatment was more effective than infusion of factor VIII itself. </p><p>Riddell et al. (2009) noted that patients with VWF type 2CB, which is characterized by clinically significant bleeding episodes due to a mutant VWF protein with defective collagen binding, show good functional response to treatment with DDAVP. DDAVP causes a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remains. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Verweij et al. (1988) used RFLPs to demonstrate that the mutation in von Willebrand disease type 2A is in the gene for von Willebrand factor on chromosome 12p13. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Von Willebrand Disease Type 2A</em></strong></p><p>
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Mutations causing the enhanced proteolysis phenotype lie within or near domain A2 (exon 28) of the VWF gene, which is the site of the ADAMTS13 (604134) cleavage sequence between residues tyr1605 and met1606. Mutations interfering with multimerization occur in regions involved in dimer or multimer assembly, such as the VWF propeptide, the N-terminal D3 domain, the A2 domain, and the C terminus (James and Lillicrap, 2008). </p><p>In affected members of a family with von Willebrand disease type 2A, Iannuzzi et al. (1991) identified a 4883T-C heterozygous mutation in the VWF (I865T; 613160.0001). The I865R substitution was located immediately adjacent to 2 other previously identified mutations that also result in type 2A von Willebrand disease (R834W, 613160.0002 and V844D, 613160.0003; Ginsburg et al., 1989), suggesting a clustering for these mutations in a portion of the protein critical for proteolysis. </p><p>Dent et al. (1990) noted that the I865T, R834W, and V844D mutations are located within a 32-amino acid segment in the midportion of the 2,813-amino acid VWF coding sequence. Type 2A von Willebrand disease is characterized by normal or only moderately decreased levels of von Willebrand factor, the absence of large and intermediate VWF multimers, and increased VWF proteolysis with an increase in the plasma levels of the 176-kD VWF proteolytic fragment. The ADAMTS13 (604134) proteolytic-cleavage site is located between tyr842 and met843 (numbering based on the mature protein). </p><p><strong><em>Von Willebrand Disease Type 2A/IIE</em></strong></p><p>
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Schneppenheim et al. (2010) reported a high frequency (29%) of VWD type 2A subtype IIE among patients with type 2A studied in their laboratory. Type IIE is associated with a reduction of high molecular weight (HMW) VWF multimers and a lack of outer proteolytic bands on gel electrophoresis, indicating reduced proteolysis. Genetic analysis of 38 such index cases identified 22 different mutations in the VWF gene, most of them affecting cysteine residues clustered in the D3 domain. The most common mutation was Y1146C (613160.0039), which was found in 12 (32%) probands. In vitro expression studies indicated that the Y1146C-mutant protein caused a severe reduction in or lack of HMW monomers and decreased secreted VWF antigen levels. However, clinical symptoms were heterogeneous among carriers, ranging from mild to severe bleeding. Schneppenheim et al. (2010) suggested that several mechanisms likely act in concert to produce subtype IIE, including decreased secretion of VWF, the change of a cysteine residue which may impact multimerization, and decreased half-life of the mutant protein. Altered ADAMTS13-mediated proteolysis did not appear to be a major primary factor. </p><p><strong><em>Von Willebrand Disease Type 2B</em></strong></p><p>
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Mutations causing VWD type 2B tend to cluster within or near the A1 domain of the VWF gene, which mediates platelet GP1BA (606672) binding. The mutations appear to enhance platelet binding of VWF by stabilizing the bound conformation (Sadler et al., 2006). </p><p>In patients with VWD type 2B, Randi et al. (1991) identified 3 different heterozygous mutations in exon 28 of the VWF gene (613160.0005-613160.0007) within the domain that interacts with platelet glycoprotein GP1BA, resulting in a loss of function. Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. The region of VWF that binds to GP1BA has been localized to a peptide including amino acids 480 to 718 of the mature subunit that is encoded by exon 28. </p><p>In affected members of a Swedish family (Holmberg et al., 1986) and a German family with a variant of VWD type 2B, Holmberg et al. (1993) identified a heterozygous mutation in the VWF gene (P1266L; 613160.0033). The phenotype was unique in that there was a mild bleeding disorder, and laboratory studies showed that platelets aggregated at much lower ristocetin concentrations than normal. </p><p><strong><em>Von Willebrand Disease Type 2M</em></strong></p><p>
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In a French mother and son with VWD type 2M, Stepanian et al. (2003) identified a heterozygous mutation in the VWF gene (S1285F; 613160.0030) that altered the folding of the A1 loop and prevented the correct exposure of VWF binding sites to GP1BA. The findings were consistent with a loss of function. </p><p><strong><em>Von Willebrand Disease Type 2N</em></strong></p><p>
|
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Mutations that cause VWD type 2N usually occur in the F8-binding site of VWF, which lies between ser764 and arg1035. However, mutations outside of this region have also been reported (Hilbert et al., 2004). </p><p>In a 50-year-old French woman with VWD type 2N reported by Mazurier et al. (1990), Gaucher et al. (1991) identified a homozygous mutation in the VWF gene (T28M in the mature subunit; 613160.0011). </p><p>Mazurier et al. (2002) reported a 20-year-old French woman with VWD type 2N who was compound heterozygosity for 2 mutations in the VWF gene (Y357X, 613160.0035 and C1060R, 613160.0036). She had very low levels of VWF and F8, and absent binding of VWF to F8. Clinical features included epistaxis, hematomas, and hematemesis throughout childhood. The diagnosis was complicated at first because 2 male first cousins had F8 deficiency (306700) due to a hemizygous mutation in the F8 gene (C179G; 300841.0268). </p><p>Hilbert et al. (2004) reported 2 unrelated French patients with type 2N VWD who were compound heterozygous for R854Q (613160.0013) and another pathogenic mutation (Y795C, 613160.0031 and C804F, 613160.0032, respectively). </p><p><strong><em>Von Willebrand Disease Type 2CB</em></strong></p><p>
|
|
In affected members of 2 unrelated families with von Willebrand disease type 2CB, Riddell et al. (2009) identified heterozygous mutations in the collagen-binding A3 domain of the VWF gene (W1745C; 613160.0040 and S1783A; 613160.0042, respectively). The authors noted that VWD type 2M is associated with mutations in the A1 domain of VWF. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Rayes et al. (2010) and Golder et al. (2010) independently developed mouse models of VWD type 2B that recapitulated the human phenotype. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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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Asakura et al. (1987); Cooney et al. (1991); Donner et al. (1991);
|
|
Donner et al. (1992); Kyrle et al. (1988); Lavergne et al. (1992);
|
|
Mazurier et al. (1990); Montgomery et al. (1982); Montgomery and
|
|
Zimmerman (1978); Murray et al. (1992); Ruggeri et al. (1982);
|
|
Ruggeri et al. (1982); Ruggeri et al. (1980); Ruggeri and Zimmerman
|
|
(1980); Schneppenheim et al. (1996); Schneppenheim et al. (2000);
|
|
Schneppenheim et al. (1995); Takahashi et al. (1980); Tuley et al.
|
|
(1991); Weinger et al. (1981); Zieger et al. (1997)
|
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>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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Asakura, A., Harrison, J., Gomperts, E., Abildgaard, C.
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<strong>Type IIA von Willebrand disease with apparent recessive inheritance.</strong>
|
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Blood 69: 1419-1420, 1987.
|
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|
|
|
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[PubMed: 3105622]
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|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chey, W. D., Hasler, W. L., Bockenstedt, P. L.
|
|
<strong>Angiodysplasia and von Willebrand's disease type IIB treated with estrogen/progesterone therapy.</strong>
|
|
Am. J. Hemat. 41: 276-279, 1992.
|
|
|
|
|
|
[PubMed: 1288289]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830410410]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D.
|
|
<strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong>
|
|
J. Clin. Invest. 87: 1227-1233, 1991.
|
|
|
|
|
|
[PubMed: 1672694]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115123]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dent, J. A., Berkowitz, S. D., Ware, J., Kasper, C. K., Ruggeri, Z. M.
|
|
<strong>Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 6306-6310, 1990. Note: Erratum: Proc. Nat. Acad. Sci. 87: 9508 only, 1990.
|
|
|
|
|
|
[PubMed: 2385594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.16.6306]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donner, M., Andersson, A.-M., Kristoffersson, A.-C., Nilsson, I. M., Dahlback, B., Holmberg, L.
|
|
<strong>An arg545-to-cys substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease.</strong>
|
|
Europ. J. Haemat. 47: 342-345, 1991.
|
|
|
|
|
|
[PubMed: 1761120]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0609.1991.tb01858.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donner, M., Holmberg, L., Nilsson, I. M.
|
|
<strong>Type IIB von Willebrand's disease with probable autosomal recessive inheritance and presenting as thrombocytopenia in infancy.</strong>
|
|
Brit. J. Haemat. 66: 349-354, 1987.
|
|
|
|
|
|
[PubMed: 3497666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1987.tb06922.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L.
|
|
<strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong>
|
|
Brit. J. Haemat. 82: 58-65, 1992.
|
|
|
|
|
|
[PubMed: 1419803]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb04594.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C.
|
|
<strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong>
|
|
Blood 77: 1937-1941, 1991.
|
|
|
|
|
|
[PubMed: 2018834]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y.
|
|
<strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.
|
|
|
|
|
|
[PubMed: 2786201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.86.10.3723]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Golder, M., Pruss, C. M., Hegadorn, C., Mewburn, J., Laverty, K., Sponagle, K., Lillicrap, D.
|
|
<strong>Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.</strong>
|
|
Blood 115: 4862-4869, 2010.
|
|
|
|
|
|
[PubMed: 20371742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-11-253120]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goodeve, A. C.
|
|
<strong>The genetic basis of von Willebrand disease.</strong>
|
|
Blood Rev. 24: 123-134, 2010.
|
|
|
|
|
|
[PubMed: 20409624]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.blre.2010.03.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gralnick, H. R., Williams, S. B., McKeown, L. P., Rick, M. E., Maisonneuve, P., Jenneau, C., Sultan, Y.
|
|
<strong>Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.</strong>
|
|
J. Clin. Invest. 76: 1522-1529, 1985.
|
|
|
|
|
|
[PubMed: 2932469]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112132]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, J. D., Willis, D. W., Evatt, B. L., Jackson, D. W.
|
|
<strong>Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.</strong>
|
|
Thromb. Haemost. 57: 332-336, 1987.
|
|
|
|
|
|
[PubMed: 3116703]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease.
|
|
<strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong>
|
|
Brit. J. Haemat. 127: 184-189, 2004.
|
|
|
|
|
|
[PubMed: 15461624]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2004.05187.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M.
|
|
<strong>Von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong>
|
|
Blood 68: 668-672, 1986.
|
|
|
|
|
|
[PubMed: 3488775]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M.
|
|
<strong>Von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong>
|
|
J. Clin. Invest. 91: 2169-2177, 1993.
|
|
|
|
|
|
[PubMed: 8486782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI116443]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Nilsson, I. M., Borge, L., Gunnarsson, M., Sjorin, E.
|
|
<strong>Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in type IIB von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 309: 816-821, 1983.
|
|
|
|
|
|
[PubMed: 6412139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198310063091402]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D.
|
|
<strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong>
|
|
Am. J. Hum. Genet. 48: 757-763, 1991.
|
|
|
|
|
|
[PubMed: 1673047]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C.
|
|
<strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong>
|
|
Blood 113: 3348-3351, 2009.
|
|
|
|
|
|
[PubMed: 19060241]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-06-165233]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
James, P., Lillicrap, D.
|
|
<strong>The role of molecular genetics in diagnosing von Willebrand disease.</strong>
|
|
Semin. Thromb. Hemost. 34: 502-508, 2008.
|
|
|
|
|
|
[PubMed: 19085649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1055/s-0028-1103361]
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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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Kyrle, P. A., Niessner, H., Dent, J., Panzer, S., Brenner, B., Zimmerman, T. S., Lechner, K.
|
|
<strong>IIB von Willebrand's disease: pathogenetic and therapeutic studies.</strong>
|
|
Brit. J. Haemat. 69: 55-59, 1988.
|
|
|
|
|
|
[PubMed: 3132965]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb07602.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lacombe, M., D'Angelo, G.
|
|
<strong>Etudes sur une thrombopathie familiale.</strong>
|
|
Nouv. Rev. Franc. Hemat. 3: 611-614, 1963.
|
|
|
|
|
|
[PubMed: 14091541]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lavabre-Bertrand, T., Navarro, M., Blanc, P., Larrey, D., Michel, H., Rouanet, C.
|
|
<strong>Von Willebrand's disease, digestive angiodysplasia, and estrogen-progesterone treatment. (Letter)</strong>
|
|
Am. J. Hemat. 46: 254-255, 1994.
|
|
|
|
|
|
[PubMed: 8192164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830460325]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lavergne, J.-M., De Paillette, L., Bahnak, B. R., Ribba, A.-S., Fressinaud, E., Meyer, D., Pietu, G.
|
|
<strong>Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.</strong>
|
|
Brit. J. Haemat. 82: 66-72, 1992.
|
|
|
|
|
|
[PubMed: 1419804]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb04595.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lillicrap, D.
|
|
<strong>Genotype/phenotype association in von Willebrand disease: is the glass half full or empty?</strong>
|
|
J. Thromb. Haemost. 7 (suppl. 1): 65-70, 2009.
|
|
|
|
|
|
[PubMed: 19630771]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1538-7836.2009.03367.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lopez-Fernandez, M. F., Blanco-Lopez, M. J., Castineira, M. P., Batlle, J.
|
|
<strong>Further evidence for recessive inheritance of von Willebrand disease with abnormal binding of von Willebrand factor to factor VIII.</strong>
|
|
Am. J. Hemat. 40: 20-27, 1992.
|
|
|
|
|
|
[PubMed: 1566742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830400105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mannucci, P. M.
|
|
<strong>Treatment of von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 351: 683-694, 2004.
|
|
|
|
|
|
[PubMed: 15306670]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMra040403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M.
|
|
<strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong>
|
|
Blood 75: 20-26, 1990.
|
|
|
|
|
|
[PubMed: 2104761]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Gaucher, C., Jorieux, S., Parquet-Gernez, A., Goudemand, M.
|
|
<strong>Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.</strong>
|
|
Brit. J. Haemat. 76: 372-379, 1990.
|
|
|
|
|
|
[PubMed: 2124499]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb06371.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J.
|
|
<strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong>
|
|
Brit. J. Haemat. 119: 390-392, 2002.
|
|
|
|
|
|
[PubMed: 12406074]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2002.03819.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C.
|
|
<strong>Von Willebrand disease masquerading as haemophilia A.</strong>
|
|
Thromb. Haemost. 67: 391-396, 1992.
|
|
|
|
|
|
[PubMed: 1631785]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milton, J. G., Frojmovic, M. M., Tang, S. S., White, J. G.
|
|
<strong>Spontaneous platelet aggregation in a hereditary giant platelet syndrome (MPS).</strong>
|
|
Am. J. Path. 114: 336-345, 1984.
|
|
|
|
|
|
[PubMed: 6696046]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milton, J. G., Frojmovic, M. M.
|
|
<strong>Shape-changing agents produce abnormally large platelets in a hereditary 'giant platelets syndrome (MPS)'.</strong>
|
|
J. Lab. Clin. Med. 93: 154-161, 1979.
|
|
|
|
|
|
[PubMed: 759524]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montgomery, R. R., Hathaway, W. E., Johnson, J., Jacobson, L., Muntean, W.
|
|
<strong>A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity.</strong>
|
|
Blood 60: 201-207, 1982.
|
|
|
|
|
|
[PubMed: 6805535]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montgomery, R. R., Zimmerman, T. S.
|
|
<strong>Von Willebrand's disease antigen II: a new plasma and platelet antigen deficient in severe von Willebrand's disease.</strong>
|
|
J. Clin. Invest. 61: 1498-1507, 1978.
|
|
|
|
|
|
[PubMed: 307007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI109070]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murray, E. W., Giles, A. R., Bridge, P. J., Peake, I. R., Lillicrap, D. P.
|
|
<strong>Cosegregation of von Willebrand factor gene polymorphisms and possible germinal mosaicism in type IIB von Willebrand disease.</strong>
|
|
Blood 77: 1476-1483, 1991.
|
|
|
|
|
|
[PubMed: 2009368]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murray, E. W., Giles, A. R., Lillicrap, D.
|
|
<strong>Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease.</strong>
|
|
Am. J. Hum. Genet. 50: 199-207, 1992.
|
|
|
|
|
|
[PubMed: 1729889]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Othman, M., Favaloro, E. J.
|
|
<strong>Genetics of type 2B von Willebrand disease: 'true 2B,' 'tricky 2B,' or 'not 2B.' What are the modifiers of the phenotype?</strong>
|
|
Semin. Thromb. Hemost. 34: 520-531, 2008.
|
|
|
|
|
|
[PubMed: 19085651]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1055/s-0028-1103363]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E.
|
|
<strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong>
|
|
J. Clin. Invest. 87: 1220-1226, 1991.
|
|
|
|
|
|
[PubMed: 2010538]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115122]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rayes, J., Hollestelle, M. J., Legendre, P., Marx, I., de Groot, P. G., Christophe, O. D., Lenting, P. J., Denis, C. V.
|
|
<strong>Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B.</strong>
|
|
Blood 115: 4870-4877, 2010.
|
|
|
|
|
|
[PubMed: 20200350]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-11-254193]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A.
|
|
<strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong>
|
|
Blood 114: 3489-3496, 2009.
|
|
|
|
|
|
[PubMed: 19687512]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-10-184317]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Lombardi, R., Gatti, L., Bader, R., Valsecchi, C., Zimmerman, T. S.
|
|
<strong>Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von Willebrand factor.</strong>
|
|
Blood 60: 1453-1456, 1982.
|
|
|
|
|
|
[PubMed: 6982737]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S.
|
|
<strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong>
|
|
J. Clin. Invest. 70: 1124-1127, 1982.
|
|
|
|
|
|
[PubMed: 6982283]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/jci110700]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Pareti, F. I., Mannucci, P. M., Ciavarella, N., Zimmerman, T. S.
|
|
<strong>Heightened interaction between platelets and factor VIII von Willebrand factor in a new subtype of von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 302: 1047-1051, 1980.
|
|
|
|
|
|
[PubMed: 6767976]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198005083021902]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong>
|
|
J. Clin. Invest. 65: 1318-1325, 1980.
|
|
|
|
|
|
[PubMed: 6773982]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI109795]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saba, H. I., Saba, S. R., Dent, J., Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.</strong>
|
|
Blood 66: 282-286, 1985.
|
|
|
|
|
|
[PubMed: 3926021]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others.
|
|
<strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong>
|
|
J. Thromb. Haemost. 4: 2103-2114, 2006.
|
|
|
|
|
|
[PubMed: 16889557]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1538-7836.2006.02146.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Brassard, J., Krey, S., Budde, U., Kunicki, T. J., Holmberg, L., Ware, J., Ruggeri, Z. M.
|
|
<strong>Defective dimerization of von Willebrand factor subunits due to a cys-to-arg mutation in type IID von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 3581-3586, 1996.
|
|
|
|
|
|
[PubMed: 8622978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.8.3581]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R.
|
|
<strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong>
|
|
Thromb. Haemost. 83: 136-140, 2000.
|
|
|
|
|
|
[PubMed: 10669167]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U.
|
|
<strong>:A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong>
|
|
Blood 115: 4894-4901, 2010.
|
|
|
|
|
|
[PubMed: 20351307]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-07-226324]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Thomas, K. B., Krey, S., Budde, U., Jessat, U., Sutor, A. H., Zieger, B.
|
|
<strong>Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.</strong>
|
|
Hum. Genet. 95: 681-686, 1995.
|
|
|
|
|
|
[PubMed: 7789955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00209487]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D.
|
|
<strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 120: 643-651, 2003.
|
|
|
|
|
|
[PubMed: 12588351]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2003.04168.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takahashi, H., Sakuragawa, N., Shibata, A.
|
|
<strong>Von Willebrand disease with an increased ristocetin-induced platelet aggregation and a qualitative abnormality of the factor VIII protein.</strong>
|
|
Am. J. Hemat. 8: 299-308, 1980.
|
|
|
|
|
|
[PubMed: 6774612]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830080308]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tuley, E. A., Gaucher, C., Jorieux, S., Worrall, N. K., Sadler, J. E., Mazurier, C.
|
|
<strong>Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 6377-6381, 1991.
|
|
|
|
|
|
[PubMed: 1906179]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.14.6377]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verweij, C. L., Quadt, R., Briet, E., Dubbeldam, K., van Ommen, G. B., Pannekoek, H.
|
|
<strong>Genetic linkage of two intragenic restriction fragment length polymorphisms with von Willebrand's disease type IIA: evidence for a defect in the von Willebrand factor gene.</strong>
|
|
J. Clin. Invest. 81: 1116-1121, 1988.
|
|
|
|
|
|
[PubMed: 2895123]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI113425]
|
|
|
|
|
|
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<p class="mim-text-font">
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Warkentin, T. E., Moore, J. C., Morgan, D. G.
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<strong>Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link?</strong>
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|
Lancet 340: 35-37, 1992.
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|
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|
[PubMed: 1351610]
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[Full Text: https://doi.org/10.1016/0140-6736(92)92434-h]
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Weinger, R. S., Cimo, P. L., Moake, J. L., Olson, J. D., Heller, M. S.
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<strong>Type IIB von Willebrand's disease: unusual response to cryoprecipitate infusion.</strong>
|
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Ann. Intern. Med. 94: 47-50, 1981.
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[PubMed: 6778284]
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[Full Text: https://doi.org/10.7326/0003-4819-94-1-47]
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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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Weiss, J. G., Sussman, I. I.
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<strong>A new von Willebrand variant (type I, New York): increased ristocetin-induced platelet aggregation and plasma von Willebrand factor containing the full range of multimers.</strong>
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Blood 68: 149-156, 1986.
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[PubMed: 3487353]
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Wylie, B., Gibson, J., Uhr, E., Kronenberg, H.
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<strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong>
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Pathology 20: 62-63, 1988.
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[PubMed: 3259690]
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[Full Text: https://doi.org/10.3109/00313028809085199]
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Zieger, B., Budde, U., Jessat, U., Zimmermann, R., Simon, M., Katzel, R., Sutor, A. H.
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<strong>New families with von Willebrand disease type 2M (Vicenza).</strong>
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Thromb. Res. 87: 57-64, 1997.
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[PubMed: 9253800]
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[Full Text: https://doi.org/10.1016/s0049-3848(97)00104-7]
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</li>
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<li>
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Zimmerman, T. S., Dent, J. A., Ruggeri, Z. M., Nannini, L. H.
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<strong>Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE).</strong>
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J. Clin. Invest. 77: 947-951, 1986.
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[PubMed: 3485111]
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[Full Text: https://doi.org/10.1172/JCI112394]
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Zimmerman, T. S., Ruggeri, Z. M.
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<strong>Von Willebrand disease.</strong>
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Hum. Path. 18: 140-152, 1987.
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[PubMed: 3100416]
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[Full Text: https://doi.org/10.1016/s0046-8177(87)80332-5]
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Cassandra L. Kniffin - updated : 4/29/2013<br>Cassandra L. Kniffin - updated : 5/10/2011<br>Cassandra L. Kniffin - updated : 10/8/2010
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Cassandra L. Kniffin : 9/8/2010
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carol : 02/22/2022<br>carol : 08/07/2019<br>alopez : 08/06/2019<br>carol : 10/21/2016<br>alopez : 05/03/2013<br>ckniffin : 5/1/2013<br>ckniffin : 4/29/2013<br>terry : 8/9/2012<br>wwang : 6/13/2011<br>ckniffin : 5/10/2011<br>carol : 4/7/2011<br>terry : 1/7/2011<br>terry : 11/24/2010<br>wwang : 11/2/2010<br>ckniffin : 10/8/2010<br>terry : 10/8/2010<br>carol : 10/4/2010<br>ckniffin : 9/29/2010
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