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Entry
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- #147060 - HYPER-IgE SYNDROME 1, AUTOSOMAL DOMINANT, WITH RECURRENT INFECTIONS; HIES1
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- OMIM
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<p>
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<span class="h4">#147060</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/147060"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS147060"> <strong>Phenotypic Series</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="#pathogenesis">Pathogenesis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#diagnosis">Diagnosis</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="#nomenclature">Nomenclature</a>
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<a href="#history">History</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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<div style="display: table-cell;">External Links</div>
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</h4>
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<div style="display: table-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=HYPER-IgE SYNDROME 1, AUTOSOMAL DOMINANT, WITH RECURRENT INFECTIONS" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=839&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK25507/" 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/8588" 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/autosomal-dominant-hyper-ige-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=147060[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2314" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/38d19ddd-9484-4ced-bdc5-b3456a856005/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div 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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<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:3261" 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/147060" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:3261" 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 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="mimCellLines">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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<div id="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:147060" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 50926003<br />
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<strong>ICD10CM:</strong> D82.4<br />
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<strong>ORPHA:</strong> 2314<br />
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<strong>DO:</strong> 3261<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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147060
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</span>
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</span>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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HYPER-IgE SYNDROME 1, AUTOSOMAL DOMINANT, WITH RECURRENT INFECTIONS; HIES1
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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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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT<br />
|
|
HYPER-IgE SYNDROME, AUTOSOMAL DOMINANT<br />
|
|
HIES, AUTOSOMAL DOMINANT<br />
|
|
JOB SYNDROME
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
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|
|
|
|
|
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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/17/576?start=-3&limit=10&highlight=576">
|
|
17q21.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hyper-IgE syndrome 1, autosomal dominant, with recurrent infections
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/147060"> 147060 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
STAT3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/102582"> 102582 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/147060" 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">
|
|
|
|
<a href="/phenotypicSeries/PS147060" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</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/147060" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/147060" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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 />
|
|
|
|
</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> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Coarse facies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span><br /> -
|
|
Asymmetric face <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15253005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15253005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1306710&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1306710</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000324</a>]</span><br /> -
|
|
Prominent forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837260</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011220</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011220</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=a2091161c29564b62e12b608022a4044" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Forehead,Prominent-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=a2091161c29564b62e12b608022a4044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Mild prognathism <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675138&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675138</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/72855002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">72855002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109504005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109504005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22810007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22810007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.213" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.213</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.23</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2aaef6d7371d3478c5adcef40ea1e36f" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Prognathism-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2aaef6d7371d3478c5adcef40ea1e36f" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Broad nose <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249321001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249321001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000445" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000445</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000445" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000445</a>]</span><br /> -
|
|
Thickening of the soft tissue of the nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675139&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675139</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- High-arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Teeth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Retained primary teeth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57650002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57650002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1172951004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1172951004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266050&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266050</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006335" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006335</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006335" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006335</a>]</span><br /> -
|
|
Reduced resorption of primary tooth roots <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675140&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675140</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
|
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|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Recurrent sinopulmonary infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846546&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846546</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005425" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005425</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005425" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005425</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Lung </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pneumatocele formation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675145&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675145</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
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|
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Joint hyperextensibility <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span><br /> -
|
|
Decreased bone mineral density <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312894000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312894000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2674432&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2674432</a>, <a href="https://bioportal.bioontology.org/search?q=C0029453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029453</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000938" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000938</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004349" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004349</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004349" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004349</a>]</span><br /> -
|
|
Recurrent fractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788192009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788192009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771485007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771485007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5468008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5468008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016655&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016655</a>, <a href="https://bioportal.bioontology.org/search?q=C3805574&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805574</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002757" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002757</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002757" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002757</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skull </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Craniosynostosis (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57219006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57219006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1421244&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1421244</a>, <a href="https://bioportal.bioontology.org/search?q=C5848303&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848303</a>, <a href="https://bioportal.bioontology.org/search?q=C0010278&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010278</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001363" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001363</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0005458" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005458</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001363" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001363</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br /> -
|
|
Vertebral body abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857648&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857648</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">
|
|
|
|
- Eczema, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673465&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673465</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43116000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43116000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L30.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L30.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000964" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000964</a>]</span><br /> -
|
|
Recurrent skin abscesses <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675144&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675144</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> IMMUNOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Recurrent Staphylococcus aureus infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673462&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673462</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002726</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002726</a>]</span><br /> -
|
|
Abscesses are 'cold,' lacking erythema, heat, and swelling <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675141&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675141</a>]</span><br /> -
|
|
Recurrent fungal infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844384&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844384</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002841" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002841</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002841" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002841</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased serum IgE <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673464</a>]</span><br /> -
|
|
Eosinophilia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386789004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386789004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.10</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014457&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014457</a>, <a href="https://bioportal.bioontology.org/search?q=C2240374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240374</a>, <a href="https://bioportal.bioontology.org/search?q=C1306759&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1306759</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001880" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001880</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001880" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001880</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the signal transducer and activator of transcription-3 gene (STAT3, <a href="/entry/102582#0001">102582.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<h5>
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Hyper-IgE recurrent infection syndrome
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- <a href="/phenotypicSeries/PS147060">PS147060</a>
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- 6 Entries
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</h5>
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
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<thead>
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<tr>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Location</strong>
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</th>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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<strong>Phenotype</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Inheritance</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />mapping key</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />MIM number</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Gene/Locus</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Gene/Locus<br />MIM number</strong>
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/1190?start=-3&limit=10&highlight=1190"> 1q21.3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/618944"> Hyper-IgE syndrome 5, autosomal recessive, with recurrent infections </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/618944"> 618944 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/147880"> IL6R </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/147880"> 147880 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/5/177?start=-3&limit=10&highlight=177"> 5q11.2 </a>
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|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/618523"> Hyper-IgE syndrome 4B, autosomal recessive, with recurrent infections </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/618523"> 618523 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/600694"> IL6ST </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/600694"> 600694 </a>
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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|
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<a href="/geneMap/5/177?start=-3&limit=10&highlight=177"> 5q11.2 </a>
|
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|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/619752"> Hyper-IgE syndrome 4A, autosomal dominant, with recurrent infections </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619752"> 619752 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600694"> IL6ST </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600694"> 600694 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/9?start=-3&limit=10&highlight=9"> 9p24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/243700"> Hyper-IgE syndrome 2, autosomal recessive, with recurrent infections </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/243700"> 243700 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611432"> DOCK8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611432"> 611432 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/576?start=-3&limit=10&highlight=576"> 17q21.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/147060"> Hyper-IgE syndrome 1, autosomal dominant, with recurrent infections </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/147060"> 147060 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/102582"> STAT3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/102582"> 102582 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/20/219?start=-3&limit=10&highlight=219"> 20q11.22 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618282"> Hyper-IgE syndrome 3, autosomal recessive, with recurrent infections </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618282"> 618282 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
|
|
<a href="/entry/618269"> ZNF341 </a>
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618269"> 618269 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
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</tbody>
|
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</table>
|
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</div>
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<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
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</div>
|
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
|
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<div id="mimTextFold" class="collapse in ">
|
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant hyper-IgE syndrome-1 with recurrent infections (HIES1) is caused by heterozygous mutation in the STAT3 gene (<a href="/entry/102582">102582</a>) on chromosome 17q21. The mutations cause a dominant-negative effect.</p><p>Heterozygous gain-of-function mutations in the STAT3 gene cause an infantile-onset multisystem autoimmune disease (ADMIO1; <a href="/entry/615952">615952</a>).</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
|
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Hyper-IgE syndrome-1 with recurrent infections (HIES1) is an autosomal dominant immunologic disorder characterized by chronic eczema (atopy), recurrent Staphylococcal infections, increased serum IgE, and eosinophilia. Other more variable immunologic abnormalities include defective granulocyte chemotaxis, abnormalities in T-lymphocyte subgroups, impaired antibody production, and decreased production of or response to certain cytokines. Importantly, the same immune system defects are not found in all patients. Some patients may have a distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures (<a href="#9" class="mim-tip-reference" title="Buckley, R. H., Wray, B. B., Belmaker, E. Z. <strong>Extreme hyperimmunoglobulin E and undue susceptibility to infection.</strong> Pediatrics 49: 59-70, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5059313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5059313</a>]" pmid="5059313">Buckley et al., 1972</a>; <a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10053178+5059313" 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>Genetic Heterogeneity of Hyper-IgE Syndrome</em></strong></p><p>
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See also HIES2 (<a href="/entry/243700">243700</a>), caused by mutation in the DOCK8 gene (<a href="/entry/611432">611432</a>); HIES3 (<a href="/entry/618282">618282</a>), caused by mutation in the ZNF341 gene (<a href="/entry/618269">618269</a>); HIES4A (<a href="/entry/619752">619752</a>) and HIES4B (<a href="/entry/618523">618523</a>), both caused by mutation in the IL6ST gene (<a href="/entry/600694">600694</a>); HIES5 (<a href="/entry/618944">618944</a>), caused by mutation in the IL6R gene (<a href="/entry/147880">147880</a>); and HIES6 (<a href="/entry/620532">620532</a>), caused by mutation in the STAT6 gene (<a href="/entry/601512">601512</a>).</p>
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<p><a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a> reported 2 unrelated girls with lifelong histories of indolent Staphylococcal abscesses. Both had eczema soon after birth and had persistent weeping lesions on the ears and face. The abscesses were characterized as 'cold' because of the lack of surrounding warmth, erythema, or tenderness. Both girls had red hair and were fair-skinned. The authors suggested a defect in local resistance to Staphylococcal infection. Further study of these girls by <a href="#41" class="mim-tip-reference" title="White, L. R., Iannetta, A., Kaplan, E. L., Davis, S. D., Wedgwood, R. J. <strong>Leucocytes in Job's syndrome. (Letter)</strong> Lancet 293: 630 only, 1969. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4180157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4180157</a>] [<a href="https://doi.org/10.1016/s0140-6736(69)91577-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4180157">White et al. (1969)</a> revealed normal leukocyte functions. However, <a href="#20" class="mim-tip-reference" title="Hill, H. R., Ochs, H. D., Quie, P. G., Clark, R. A., Pabst, H. F., Klebanoff, S. J., Wedgwood, R. J. <strong>Defect in neutrophil granulocyte chemotaxis in Job's syndrome of recurrent 'cold' staphylococcal abscesses.</strong> Lancet 304: 617-619, 1974. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4137601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4137601</a>] [<a href="https://doi.org/10.1016/s0140-6736(74)91942-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4137601">Hill et al. (1974)</a> and <a href="#21" class="mim-tip-reference" title="Hill, H. R., Quie, P. G. <strong>Raised serum-IgE levels and defective neutrophil chemotaxis in three children with eczema and recurrent bacterial infections.</strong> Lancet 303: 183-187, 1974. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4129875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4129875</a>] [<a href="https://doi.org/10.1016/s0140-6736(74)92493-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4129875">Hill and Quie (1974)</a> found a defect in neutrophil granulocyte chemotaxis and very high serum IgE levels in 4 girls with the disorder; 2 of the girls had been reported by <a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4180157+4161105+4137601+4129875" 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="#35" class="mim-tip-reference" title="Renner, E. D., Torgerson, T. R., Rylaarsdam, S., Anover-Sombke, S., Golob, K., LaFlam, T., Zhu, Q., Ochs, H. D. <strong>STAT3 mutation in the original patient with Job's syndrome. (Letter)</strong> New Eng. J. Med. 357: 1667-1668, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17942886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17942886</a>] [<a href="https://doi.org/10.1056/NEJMc076367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17942886">Renner et al. (2007)</a> provided a follow-up of 1 of the patients reported by <a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a>. At 50 years of age, the woman had had lifelong eczema, multiple atraumatic fractures, hyperkeratotic fingernails due to candida infection, recurrent Staphylococcal abscesses, and pneumonia with lung abscesses and pneumatocele formation. Two of her 3 sons and 1 grandson were also affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4161105+17942886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Buckley, R. H., Wray, B. B., Belmaker, E. Z. <strong>Extreme hyperimmunoglobulin E and undue susceptibility to infection.</strong> Pediatrics 49: 59-70, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5059313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5059313</a>]" pmid="5059313">Buckley et al. (1972)</a> described 2 male patients with features of Job syndrome as originally described by <a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a>. Each boy had extremely high serum IgE levels as well as immediate cutaneous hypersensitivity reactions to Staphylococcus aureus and Candida albicans. The authors also noted joint hyperextensibility and asymmetric facies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4161105+5059313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Van Scoy, R. E., Hill, H. R., Ritts, R. E., Jr., Quie, P. G. <strong>Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.</strong> Ann. Intern. Med. 82: 766-771, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1138587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1138587</a>] [<a href="https://doi.org/10.7326/0003-4819-82-6-766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1138587">Van Scoy et al. (1975)</a> described a 20-year-old woman and her daughter who had recurrent bacterial infections and chronic mucocutaneous candidiasis. Laboratory studies showed marked elevation of serum IgE, defective neutrophil chemotaxis, and impaired lymphocyte response to candida antigen. The mother's brother, father, and paternal grandfather showed mild increases in IgE and mildly depressed chemotactic activity of neutrophils. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1138587" 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="#24" class="mim-tip-reference" title="Jacobs, J. C., Norman, M. E. <strong>A familial defect of neutrophil chemotaxis with asthma, eczema, and recurrent skin infections.</strong> Pediat. Res. 11: 732-736, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/865918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">865918</a>] [<a href="https://doi.org/10.1203/00006450-197706000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="865918">Jacobs and Norman (1977)</a> found a cellular chemotactic defect in the neutrophils of both parents and 3 of 4 their children who suffered from unusually severe bacterial eczema, asthma, and recurrent bacterial skin infections, all starting in the first month of life. The parents were less severely affected. Those with severe eczema had increased IgE. All affected members had HLA-B12; the unaffected child did not. The 2 most severely affected children were homozygous for HLA-B12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=865918" 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>Osteoporosis and a propensity to bone fracture, referred to by <a href="#6" class="mim-tip-reference" title="Brestel, E. P., Klingberg, W. G., Veltri, R. W., Dorn, J. S. <strong>Osteogenesis imperfecta tarda in a child with hyper IgE syndrome.</strong> Am. J. Dis. Child. 136: 774-776, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6981344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6981344</a>] [<a href="https://doi.org/10.1001/archpedi.1982.03970450016003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6981344">Brestel et al. (1982)</a> as 'osteogenesis imperfecta tarda,' was a recognized feature of hyper-IgE syndrome. <a href="#26" class="mim-tip-reference" title="Kirchner, S. G., Sivit, C. J., Wright, P. F. <strong>Hyperimmunoglobulinemia E syndrome: association with osteoporosis and recurrent fractures.</strong> Radiology 156: 362 only, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4011897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4011897</a>] [<a href="https://doi.org/10.1148/radiology.156.2.4011897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4011897">Kirchner et al. (1985)</a> also noted the association of hyper-IgE syndrome with osteoporosis and recurrent fractures. <a href="#22" class="mim-tip-reference" title="Hoger, P. H., Boltshauser, E., Hitzig, W. H. <strong>Craniosynostosis in hyper-IgE-syndrome.</strong> Europ. J. Pediat. 144: 414-417, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4076261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4076261</a>] [<a href="https://doi.org/10.1007/BF00441793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4076261">Hoger et al. (1985)</a> described the association with craniosynostosis and discussed 3 reported cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6981344+4011897+4076261" 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="Robinson, M. F., McGregor, R., Collins, R., Cheung, K. <strong>Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease.</strong> Am. J. Med. 73: 63-70, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6979928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6979928</a>] [<a href="https://doi.org/10.1016/0002-9343(82)90927-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6979928">Robinson et al. (1982)</a> described a kindred brought to attention because of a 6-year-old girl who showed features of both the hyper-IgE syndrome and chronic granulomatous disease. Inheritance was possibly autosomal dominant. Laboratory studies showed impaired T cell responses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6979928" 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="Donabedian, H., Gallin, J. I. <strong>Mononuclear cells from patients with the hyperimmunoglobulin E-recurrent-infection syndrome produce an inhibitor of leukocyte chemotaxis.</strong> J. Clin. Invest. 69: 1155-1163, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7068851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7068851</a>] [<a href="https://doi.org/10.1172/jci110551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7068851">Donabedian and Gallin (1982)</a> presented evidence suggesting that mononuclear cells from patients with the hyper-IgE recurrent infection syndrome produced an inhibitor of leukocyte chemotaxis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7068851" 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="Donabedian, H., Gallin, J. I. <strong>The hyperimmunoglobulin E recurrent-infection (Job's) syndrome: a review of the NIH experience and the literature.</strong> Medicine 62: 195-208, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6348470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6348470</a>] [<a href="https://doi.org/10.1097/00005792-198307000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6348470">Donabedian and Gallin (1983)</a> provided a review of 13 patients with hyper-IgE syndrome examined at the National Institutes of Health. Nine of the 13 had coarse facies, with broad nasal bridge, prominent nose, and irregularly proportioned cheeks and jaws. All had recurrent skin infections, most by 3 months of age. All patients, except 1, had recurrent pneumonias, and most had recurrent bronchitis and otitis. Many patients developed pneumatoceles and most required chest tube drainage and/or lobectomies. Seven of the 13 had Candidal infections of the nails, vagina, or mouth. Three additional patients were described as having a 'variant' of the disorder due to lack of cold abscesses and serious sinopulmonary infection, declining serum IgE levels, and first appearance of infection at age 17 years, respectively. Laboratory studies showed mild to moderate eosinophilia. Impaired neutrophil chemotaxis was not a constant feature, and it was not severe when it occurred. There was some evidence for a chemotactic inhibitor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6348470" 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 hyper-IgE syndrome, <a href="#16" class="mim-tip-reference" title="Dreskin, S. C., Goldsmith, P. K., Gallin, J. I. <strong>Immunoglobulins in the hyperimmunoglobulin E and recurrent infection (Job's) syndrome: deficiency of anti-Staphylococcus aureus immunoglobulin A.</strong> J. Clin. Invest. 75: 26-34, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3871199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3871199</a>] [<a href="https://doi.org/10.1172/JCI111683" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3871199">Dreskin et al. (1985)</a> demonstrated deficiency of serum anti-Staph aureus IgA, salivary IgA, and salivary anti-Staph aureus IgA. There was an inverse correlation between the number of infections at mucosal surfaces and in adjacent lymph nodes and the levels of these substances as well as of total serum IgE and total serum IgD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3871199" 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="#29" class="mim-tip-reference" title="Lui, R. C., Inculet, R. I. <strong>Job's syndrome: a rare cause of recurrent lung abscess in childhood.</strong> Ann. Thorac. Surg. 50: 992-994, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2241394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2241394</a>] [<a href="https://doi.org/10.1016/0003-4975(90)91144-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2241394">Lui and Inculet (1990)</a> described a patient with presumed Job syndrome and recurrent lung abscess necessitating lung resection. Serum IgE levels were markedly elevated. Some of the lung abscesses appeared to be due to Staph aureus; the resected right lower lobe showed an abscess cavity with aspergilloma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2241394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Borges, W. G., Hensley, T., Carey, J. C., Petrak, B. A., Hill, H. R. <strong>The face of Job.</strong> J. Pediat. 133: 303-305, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709729</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70243-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9709729">Borges et al. (1998)</a> evaluated the facial features of 9 patients from 7 kindreds with Job syndrome. Consistent features included prominent forehead with deep-set eyes, increased width of the nose, a full lower lip, and thickening of the nose and ears. The mean alar width and outer canthal distance were significantly increased. The authors concluded that there is a recognizable face of Job syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709729" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The study of <a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al. (1999)</a> established that the hyper-IgE syndrome is a multisystem disorder. <a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al. (1999)</a> studied 30 patients with hyper-IgE syndrome and 70 of their relatives. In addition to the recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum, there are associated facial, dental, and skeletal features. Nonimmunologic features of the hyper-IgE syndrome were present in all patients older than 8 years. Failure or delay of shedding of the primary teeth owing to lack of root resorption was observed in 72%. Common findings among patients were recurrent fractures (57%), hyperextensible joints (68%), and scoliosis (in 76% of patients over 16 years of age). The classic triad of abscesses, pneumonia, and an elevated IgE level was identified in 77% of all patients and in 85% of those older than 8 years. In 6 (26%) of 23 adults, IgE levels declined over time and came closer to or fell within the normal range. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10053178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al. (1999)</a> noted the unusual facial phenotype of the hyper-IgE syndrome, which had been commented on by <a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a> and by <a href="#5" class="mim-tip-reference" title="Borges, W. G., Hensley, T., Carey, J. C., Petrak, B. A., Hill, H. R. <strong>The face of Job.</strong> J. Pediat. 133: 303-305, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709729</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70243-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9709729">Borges et al. (1998)</a>. By the age of 16 years, all of the patients studied by <a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al. (1999)</a> showed distinctive facial characteristics, including facial asymmetry with a suggestion of hemihypertrophy, prominent forehead, deep-set eyes, broad nasal bridge, wide, fleshy nasal tip, and mild prognathism. The facial skin was rough, with prominent pores. The interalar distance was increased. Head circumference also tended to be larger than normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10053178+9709729+4161105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Crosby, K., Swender, D., Chernin, L., Hafez-Khayyata, S., Ochs, H., Tcheurekdjian, H., Hostoffer, R. <strong>Signal transducer and activator of transcription 3 mutation with invasive eosinophilic disease.</strong> Allergy Rhinol. (Providence) 3: e94-e97, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23342295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23342295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23342295[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.2500/ar.2012.3.0035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23342295">Crosby et al. (2012)</a> reported a 35-year-old African-American male who presented with dysphagia that was resistant to proton pump inhibitors. The patient had a normal blood cell count and differential with 12% eosinophils and total IgE of 2728 kU/L. Additional complaints included constipation with soy and hives after eating fish. The patient had a history of recurrent infections, including staphylococcal pneumonia, as well as skin abscesses, fractures, and esophageal candidiasis. He had undergone left lung pneumonectomy secondary to pneumatocele formation after severe pneumonia. The patient had coarse facies, broad nasal bridge, moderate eczema, and hyperextensibility, and his HIES score was 53. He was found to have a ringed esophagus. Histopathologic analysis of the middle third of the esophagus revealed elevated eosinophil numbers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23342295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Asano, T., Khourieh, J., Zhang, P., Rapaport, F., Spaan, A. N., Li, J., Lei, W.-T., Pelham, S. J., Hum, D., Chrabieh, M., Han, J. E., Guerin, A., and 24 others. <strong>Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.</strong> J. Exp. Med. 218: e20202592, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34137790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34137790</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34137790[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20202592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34137790">Asano et al. (2021)</a> reported 10 patients from 7 unrelated families with HIES1 confirmed by genetic analysis. The patients, who ranged from childhood to middle age, had typical features of the disorder, including recurrent sinopulmonary infections due to bacteria and fungus, variable inflammatory skin disease, bronchiectasis, increased serum IgE, and increased eosinophils. A few patients had atypical features of the disorder, such as tuberculosis or only slightly elevated IgE. Connective tissue abnormalities and dysmorphic facies were not described, although 1 had poor overall growth and another had osteopenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34137790" 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 retrospective review of the histories of 158 patients with HIES1 with dominant-negative mutations in the STAT3 gene (STAT3DN) who were enrolled in a large natural history study, <a href="#39" class="mim-tip-reference" title="Urban, A., NCI Lymphoma Physicians Consortium, Pittaluga, S., Case Western Physicians Consortium, Freeman, A. F. <strong>Malignancy in STAT3 deficient hyper IgE syndrome.</strong> J. Clin. Immun. 42: 699-702, 2022. Note: Erratum: J. Clin. Immun. 42: 1348 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35059947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35059947</a>] [<a href="https://doi.org/10.1007/s10875-021-01197-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35059947">Urban et al. (2022)</a> identified 13 malignancies in 11 patients, giving an incidence of 8.2%. The median age of the full cohort was 25 years. The age at cancer diagnosis ranged from 4 to 65 years. Among the 13 malignancies, 8 were non-Hodgkin lymphomas (NHL) (5.1%), 2 were thyroid carcinomas (1.3%), and 3 were nonmelanoma skin cancers (1.9%). One patient had both a papillary thyroid cancer and NHL, and 1 patient had 2 types of skin cancers (basal cell and squamous cell carcinomas). All patients tolerated their cancer treatments and had achieved full remission. <a href="#39" class="mim-tip-reference" title="Urban, A., NCI Lymphoma Physicians Consortium, Pittaluga, S., Case Western Physicians Consortium, Freeman, A. F. <strong>Malignancy in STAT3 deficient hyper IgE syndrome.</strong> J. Clin. Immun. 42: 699-702, 2022. Note: Erratum: J. Clin. Immun. 42: 1348 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35059947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35059947</a>] [<a href="https://doi.org/10.1007/s10875-021-01197-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35059947">Urban et al. (2022)</a> emphasized the importance of monitoring patients with HIES1 for cancer, with consideration of a cancer diagnosis in patients with persistent or progressive lymphadenopathy or thyroid nodules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35059947" 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="#33" class="mim-tip-reference" title="Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., Davis, J., Hsu, A., Asher, A. I., O'Shea, J., Holland, S. M., Paul, W. E., Douek, D. C. <strong>Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome.</strong> Nature 452: 773-776, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337720</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337720[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337720">Milner et al. (2008)</a> showed that interleukin-17 (IL17; see <a href="/entry/603149">603149</a>) production by T cells is absent in individuals with hyper-IgE syndrome (HIES). They observed that ex vivo T cells from subjects with HIES failed to produce IL17, but not IL2 (<a href="/entry/147680">147680</a>), TNF (<a href="/entry/191160">191160</a>), or IFNG (<a href="/entry/147570">147570</a>), on mitogenic stimulation with staphylococcal enterotoxin B or on antigenic stimulation with Candida albicans or streptokinase. Purified naive T cells were unable to differentiate into IL17-producing (TH17) T helper cells in vitro and had lower expression of retinoid-related orphan receptor (ROR)-gamma-t (<a href="/entry/602943">602943</a>), which is consistent with a crucial role for STAT3 (<a href="/entry/102582">102582</a>) signaling in the generation of TH17 cells. TH17 cells are an important subset of helper T cells that are believed to be critical in the clearance of fungal and extracellular bacterial infections. Thus, <a href="#33" class="mim-tip-reference" title="Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., Davis, J., Hsu, A., Asher, A. I., O'Shea, J., Holland, S. M., Paul, W. E., Douek, D. C. <strong>Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome.</strong> Nature 452: 773-776, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337720</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337720[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337720">Milner et al. (2008)</a> concluded that the inability to produce TH17 cells is a mechanism underlying the susceptibility to recurrent infections commonly seen in HIES. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337720" 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>Independently, <a href="#31" class="mim-tip-reference" title="Ma, C. S., Chew, G. Y. J., Simpson, N., Priyadarshi, A., Wong, M., Grimbacher, B., Fulcher, D. A., Tangye, S. G., Cook, M. C. <strong>Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3.</strong> J. Exp. Med. 205: 1551-1557, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18591410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18591410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18591410[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20080218" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18591410">Ma et al. (2008)</a> and <a href="#12" class="mim-tip-reference" title="de Beaucoudrey, L., Puel, A., Filipe-Santos, O., Cobat, A., Ghandil, P., Chrabieh, M., Feinberg, J., von Bernuth, H., Samarina, A., Janniere, L., Fieschi, C., Stephan, J.-L., Boileau, C., and 33 others. <strong>Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.</strong> J. Exp. Med. 205: 1543-1550, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18591412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18591412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18591412[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20080321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18591412">de Beaucoudrey et al. (2008)</a> presented findings similar to those of <a href="#33" class="mim-tip-reference" title="Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., Davis, J., Hsu, A., Asher, A. I., O'Shea, J., Holland, S. M., Paul, W. E., Douek, D. C. <strong>Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome.</strong> Nature 452: 773-776, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337720</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337720[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337720">Milner et al. (2008)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18591410+18591412+18337720" 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>Using flow cytometric analysis, <a href="#37" class="mim-tip-reference" title="Siegel, A. M., Heimall, J., Freeman, A. F., Hsu, A. P., Brittain, E., Brenchley, J. M., Douek, D. C., Fahle, G. H., Cohen, J. I., Holland, S. M., Milner, J. D. <strong>A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.</strong> Immunity 35: 806-818, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22118528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22118528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22118528[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.immuni.2011.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22118528">Siegel et al. (2011)</a> demonstrated a significant reduction in central memory (i.e., expressing CD27, <a href="/entry/186711">186711</a>, and CD45RO, <a href="/entry/151460">151460</a>) CD4 (<a href="/entry/186940">186940</a>)-positive and CD8 (see <a href="/entry/186910">186910</a>)-positive T cells in autosomal dominant HIES patients that was not due to apoptosis or cell turnover. Stimulation of naive T cells in the presence of IL7 (<a href="/entry/146660">146660</a>) or IL15 (<a href="/entry/600554">600554</a>) failed to restore memory cell generation in HIES patients. Impaired differentiation was associated with decreased expression of 2 STAT3-responsive transcription factors, BCL6 (<a href="/entry/109565">109565</a>) and SOCS3 (<a href="/entry/604176">604176</a>). <a href="#37" class="mim-tip-reference" title="Siegel, A. M., Heimall, J., Freeman, A. F., Hsu, A. P., Brittain, E., Brenchley, J. M., Douek, D. C., Fahle, G. H., Cohen, J. I., Holland, S. M., Milner, J. D. <strong>A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.</strong> Immunity 35: 806-818, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22118528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22118528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22118528[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.immuni.2011.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22118528">Siegel et al. (2011)</a> found that HIES patients had increased risk for reactivation of varicella zoster that was associated with poor CD4-positive T-cell responses. HIES patients also had greater detectable Epstein-Barr virus (EBV) viremia that was associated with compromised T-cell memory to EBV. <a href="#37" class="mim-tip-reference" title="Siegel, A. M., Heimall, J., Freeman, A. F., Hsu, A. P., Brittain, E., Brenchley, J. M., Douek, D. C., Fahle, G. H., Cohen, J. I., Holland, S. M., Milner, J. D. <strong>A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.</strong> Immunity 35: 806-818, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22118528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22118528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22118528[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.immuni.2011.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22118528">Siegel et al. (2011)</a> concluded that STAT3 has a specific role in central memory T-cell formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22118528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Berglund, L. J., Avery, D. T., Ma, C. S., Moens, L., Deenick, E. K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P. D., Bacchetta, R., Bezrodnik, L., and 12 others. <strong>IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts.</strong> Blood 122: 3940-3950, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24159173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24159173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24159173[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2013-06-506865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24159173">Berglund et al. (2013)</a> noted that a feature of autosomal dominant HIES due to STAT3 deficiency is impaired humoral immunity following infection and vaccination. Using microarray analysis, they analyzed STAT3-deficient and normal human naive B cells after stimulation with CD40L (TNFSF5; <a href="/entry/300386">300386</a>) alone or with IL21 (<a href="/entry/605384">605384</a>). The authors observed upregulation of IL2RA (<a href="/entry/147730">147730</a>) and IL10 (<a href="/entry/124092">124092</a>) production in normal cells, but not STAT3-deficient cells. IL2 enhanced differentiation of plasma cells and Ig secretion from IL21-stimulated naive B cells. <a href="#3" class="mim-tip-reference" title="Berglund, L. J., Avery, D. T., Ma, C. S., Moens, L., Deenick, E. K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P. D., Bacchetta, R., Bezrodnik, L., and 12 others. <strong>IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts.</strong> Blood 122: 3940-3950, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24159173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24159173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24159173[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2013-06-506865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24159173">Berglund et al. (2013)</a> concluded that IL21, via STAT3, sensitizes B cells to the stimulatory effects of IL2, which may play an active role in IL21-induced B-cell differentiation. They proposed that lack of this secondary effect of IL21 may amplify humoral immunodeficiency in patients with mutations in STAT3, IL2RG (<a href="/entry/308380">308380</a>), or IL21R (<a href="/entry/605383">605383</a>) due to impaired IL21 responsiveness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24159173" 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="Lyons, J. J., Liu, Y., Ma, C. A., Yu, X., O'Connell, M. P., Lawrence, M. G., Zhang, Y., Karpe, K., Zhao, M., Siegel, A. M., Stone, K. D., Nelson, C., and 13 others. <strong>ERBIN deficiency links STAT3 and TGF-beta pathway defects with atopy in humans.</strong> J. Exp. Med. 214: 669-680, 2017. Note: Erratum: J. Exp. Med. 214: 1201 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28126831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28126831</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28126831[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20161435" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28126831">Lyons et al. (2017)</a> found that dominant-negative STAT3 mutations abolished the suppressive effect of the STAT3/ERBIN (<a href="/entry/606944">606944</a>)/SMAD2/SMAD3 complex on TGF-beta (TGFB; <a href="/entry/190180">190180</a>) signaling in vitro. Dominant-negative STAT3 mutations reduced ERBIN expression, which was associated with increased nuclear localization of SMAD2/SMAD3. Loss of ERBIN expression or presence of dominant-negative STAT3 variants in patient CD4+ T cells resulted in increased FOXP3 (<a href="/entry/300292">300292</a>) expression with increased levels of Treg cells that was dose-dependent on TGF-beta levels. SMAD3 activation and STAT3 knockdown also potentiated the transcriptional activity of GATA3 (<a href="/entry/131320">131320</a>), the canonical Th2 transcription factor, and induced expression of IL4R (<a href="/entry/147781">147781</a>). Lymphocytes from patients with dominant-negative STAT3 mutations and from individuals with decreased ERBIN expression had increased IL4R levels and increased STAT6 phosphorylation and activation in response to IL4 (<a href="/entry/147780">147780</a>), ultimately promoting B-cell development and activation, class switching to IgE, and differentiation of Th2 cells through increased GATA3 expression. Inhibition of SMAD3, TGFBR1 (<a href="/entry/190181">190181</a>), or IL4 normalized GATA3 expression in mutant lymphocytes, and the authors suggested that IL4R blockade would also be effective in reducing TGF-beta signaling. The findings linked increased TGF-beta pathway activation in both ERBIN-deficient and STAT3 mutant lymphocytes, resulting in increased Th2 cytokine expression and elevated IgE, which contribute to immune dysregulation and the atopic/allergic phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28126831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Blum, R., Geller, G., Fish, L. A. <strong>Recurrent severe staphylococcal infections, eczematoid rash: extreme elevations of IgE, eosinophilia and different chemotactic responses in two generations.</strong> J. Pediat. 90: 607-609, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/839376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">839376</a>] [<a href="https://doi.org/10.1016/s0022-3476(77)80380-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="839376">Blum et al. (1977)</a> reported hyper-IgE syndrome with recurrent severe Staphylococcal infections, eczematoid rash, and eosinophilia in 2 successive generations of a family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=839376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Buckley, R. H., Becker, W. G. <strong>Abnormalities in the regulation of human IgE synthesis.</strong> Immun. Rev. 41: 288-314, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/360511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">360511</a>] [<a href="https://doi.org/10.1111/j.1600-065x.1978.tb01469.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="360511">Buckley and Becker (1978)</a> reviewed 20 patients with HIE syndrome. Since both males and females were affected in successive generations, they suggested autosomal dominant inheritance with incomplete penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=360511" 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="Leung, D. Y. M., Geha, R. S. <strong>Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome.</strong> Hemat. Oncol. Clin. North Am. 2: 81-100, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3279022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3279022</a>]" pmid="3279022">Leung and Geha (1988)</a> reported 9 patients with the disorder. None of the patients had a family history of recurrent infections or consanguinity, indicating de novo or sporadic occurrence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3279022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al. (1999)</a> concluded that the hyper-IgE syndrome is inherited as an autosomal dominant disorder with variable expressivity. They presented pedigrees of 6 families, 4 of which had definitely affected cases in 2 successive generations. One family had affected father and son. Of 27 relatives at risk for inheriting the disorder, 10 were fully affected, 11 were unaffected, and 6 had combinations of mild immunologic, dental, and skeletal features of the hyper-IgE syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10053178" 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="#28" class="mim-tip-reference" title="Leung, D. Y. M., Geha, R. S. <strong>Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome.</strong> Hemat. Oncol. Clin. North Am. 2: 81-100, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3279022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3279022</a>]" pmid="3279022">Leung and Geha (1988)</a> reviewed cases of HIE syndrome and concluded that the most distinctive feature of the disorder is elevated serum IgE levels. They also emphasized the necessity to distinguish the HIE syndrome from atopic dermatitis (see, e.g., <a href="/entry/603165">603165</a>), a disorder with which it is frequently confused. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3279022" 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>Distinction from Atopic Dermatitis</em></strong></p><p>
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<a href="#18" class="mim-tip-reference" title="Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M. <strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong> New Eng. J. Med. 340: 692-702, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>] [<a href="https://doi.org/10.1056/NEJM199903043400904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053178">Grimbacher et al. (1999)</a> noted several distinguishing features of HIE syndrome and severe atopic dermatitis. In HIE syndrome, Staphylococcus aureus infections are deep seeded and serious, non-Staph aureus infections are frequent, respiratory allergy is rare, and onset occurs between 1 and 8 weeks. In atopic dermatitis, Staphylococcus aureus infections are superficial and involve only the skin, non-Staph aureus infections are rare, respiratory allergy is common, and onset occurs after age 2 months. Patients with HIE often have coarse facies, which is not present in patients with atopic dermatitis. Severe atopic dermatitis is at least 10 times more common than HIE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10053178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a prospective trial of levamisole in a large group of patients with Job syndrome, <a href="#13" class="mim-tip-reference" title="Donabedian, H., Alling, D. W., Gallin, J. I. <strong>Levamisole is inferior to placebo in the hyperimmunoglobulin E recurrent-infection (Job's) syndrome.</strong> New Eng. J. Med. 307: 290-292, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6806658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6806658</a>] [<a href="https://doi.org/10.1056/NEJM198207293070506" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6806658">Donabedian et al. (1982)</a> found no decrease in the propensity to infection, despite the fact that the drug clearly reversed the chemotactic defect. In a response to this report, <a href="#38" class="mim-tip-reference" title="Swim, A. T., Bradac, C., Craddock, P. R. <strong>Levamisole in Job's syndrome. (Letter)</strong> New Eng. J. Med. 307: 1528-1529, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7144828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7144828</a>] [<a href="https://doi.org/10.1056/NEJM198212093072424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7144828">Swim et al. (1982)</a> suggested that the leukocyte defect and the proneness to infection in Job syndrome may be unrelated. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7144828+6806658" 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>HIES1 is caused by mutation in the STAT3 gene, which maps to chromosome 17q21.</p><p><strong><em>Genetic Heterogeneity</em></strong></p><p>
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<a href="#19" class="mim-tip-reference" title="Grimbacher, B., Schaffer, A. A., Holland, S. M., Davis, J., Gallin, J. I., Malech, H. L., Atkinson, T. P., Belohradsky, B. H., Buckley, R. H., Cossu, F., Espanol, T., Garty, B.-Z., Matamoros, N., Myers, L. A., Nelson, R. P., Ochs, H. D., Renner, E. D., Wellinghausen, N., Puck, J. M. <strong>Genetic linkage of hyper-IgE syndrome to chromosome 4.</strong> Am. J. Hum. Genet. 65: 735-744, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441580</a>] [<a href="https://doi.org/10.1086/302547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441580">Grimbacher et al. (1999)</a> scored 19 kindreds with multiple cases of HIES for clinical and laboratory findings and genotyped the members of these 19 kindreds with polymorphic markers in a candidate region on chromosome 4. This region was selected because 1 patient with sporadic HIES plus autism and mental retardation was found to have a supernumerary marker chromosome, derived from a 15- to 20-cM interstitial deletion in 4q21. Linkage analysis in the 19 kindreds showed a maximum 2-point lod score of 3.61 at a recombination fraction of 0.0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES. Six kindreds did not show linkage to 4q, indicating genetic heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441580" 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="#34" class="mim-tip-reference" title="Minegishi, Y., Saito, M., Tsuchiya, S., Tsuge, I., Takada, H., Hara, T., Kawamura, N., Ariga, T., Pasic, S., Stojkovic, O., Metin, A., Karasuyama, H. <strong>Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.</strong> Nature 448: 1058-1062, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17676033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17676033</a>] [<a href="https://doi.org/10.1038/nature06096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17676033">Minegishi et al. (2007)</a> found that 8 of 15 unrelated nonfamilial HIES patients had heterozygous mutations in the STAT3 gene (see, e.g., <a href="/entry/102582#0001">102582.0001</a>-<a href="/entry/102582#0003">102582.0003</a>). None of the parents or sibs of the patients had the mutant STAT3 allele, suggesting that these were de novo mutations. All 5 identified mutations were located in the DNA-binding domain of STAT3. The peripheral blood cells showed defective responses to cytokines, including interleukin-6 (IL6; <a href="/entry/147620">147620</a>) and IL10, and the DNA-binding ability of STAT3 in these cells was greatly diminished. All 5 mutants were nonfunctional by themselves and showed dominant-negative effects when coexpressed with wildtype STAT3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17676033" 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="#23" class="mim-tip-reference" title="Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N., Freeman, A. F., Demidowich, A., Davis, J., Turner, M. L., Anderson, V. L., Darnell, D. N., and 13 others. <strong>STAT3 mutations in the hyper-IgE syndrome.</strong> New Eng. J. Med. 357: 1608-1619, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881745</a>] [<a href="https://doi.org/10.1056/NEJMoa073687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17881745">Holland et al. (2007)</a> collected longitudinal clinical data on patients with the hyper-IgE syndrome and their families and assayed the levels of cytokine secreted by stimulated leukocytes and the gene expression in resting and stimulated cells. These data implicated STAT3 as a candidate gene, which they then sequenced. They identified missense mutations and single-codon in-frame deletions in STAT3 in 50 familial and sporadic cases of the hyper-IgE syndrome. Eighteen discrete mutations, 5 of which were hotspots, were predicted to affect directly the DNA-binding and SRC homology-2 (SH2) domains (see, e.g., <a href="/entry/102582#0001">102582.0001</a>-<a href="/entry/102582#0006">102582.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881745" 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="#35" class="mim-tip-reference" title="Renner, E. D., Torgerson, T. R., Rylaarsdam, S., Anover-Sombke, S., Golob, K., LaFlam, T., Zhu, Q., Ochs, H. D. <strong>STAT3 mutation in the original patient with Job's syndrome. (Letter)</strong> New Eng. J. Med. 357: 1667-1668, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17942886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17942886</a>] [<a href="https://doi.org/10.1056/NEJMc076367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17942886">Renner et al. (2007)</a> demonstrated that one of the original patients with Job syndrome described by <a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a> had a heterozygous arg382-to-trp mutation (R382W; <a href="/entry/102582#0002">102582.0002</a>) in the STAT3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4161105+17942886" 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 the patient they reported with food allergies, a high score for HIES, and eosinophilic esophagitis, <a href="#10" class="mim-tip-reference" title="Crosby, K., Swender, D., Chernin, L., Hafez-Khayyata, S., Ochs, H., Tcheurekdjian, H., Hostoffer, R. <strong>Signal transducer and activator of transcription 3 mutation with invasive eosinophilic disease.</strong> Allergy Rhinol. (Providence) 3: e94-e97, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23342295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23342295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23342295[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.2500/ar.2012.3.0035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23342295">Crosby et al. (2012)</a> identified a thr389-to-ile (T389I; <a href="/entry/102582#0007">102582.0007</a>) mutation in the STAT3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23342295" 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 10 patients from 7 unrelated families with HIES1, <a href="#1" class="mim-tip-reference" title="Asano, T., Khourieh, J., Zhang, P., Rapaport, F., Spaan, A. N., Li, J., Lei, W.-T., Pelham, S. J., Hum, D., Chrabieh, M., Han, J. E., Guerin, A., and 24 others. <strong>Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.</strong> J. Exp. Med. 218: e20202592, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34137790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34137790</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34137790[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20202592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34137790">Asano et al. (2021)</a> identified heterozygous nonsense or frameshift mutations in the STAT3 gene. The patients were ascertained from several large cohorts of patients with immune disorders, and the mutations were found by exome sequencing. Detailed in vitro functional expression studies of 150 STAT3 mutations that had been identified in patients with autosomal dominant HIES1 showed that most of the canonical transcripts (95.3%) of these variants encoded STAT3 proteins with little or no STAT3 activity. Fifteen variants were putative loss-of-function alleles. Many of the variants were found to encode truncated proteins that were expressed, produced neoproteins from translation reinitiation codons, or generated isoforms from alternative transcripts. Functional studies using a luciferase assay indicated that autosomal dominant HEIS1 due to STAT3 deficiency is caused by a dominant-negative effect rather than haploinsufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34137790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between autosomal dominant hyper-IgE syndrome and variation in the ERBIN gene, see <a href="/entry/606944#0001">606944.0001</a>.</p>
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<p><a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al. (1966)</a> called the disorder 'Job syndrome' because of phenotypic similarity to the biblical figure Job: 'Satan...smote Job with sore boils from the sole of his foot unto his crown' (Job 2:7). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4161105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The first description of hyper-IgE syndrome (<a href="#11" class="mim-tip-reference" title="Davis, S. D., Schaller, J., Wedgwood, R. J. <strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong> Lancet 287: 1013-1015, 1966. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>] [<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4161105">Davis et al., 1966</a>) in girls with fair skin and red hair suggested an association with pigmentation. Later studies showed that the disorder is not associated with red hair or fair skin and that it occurs in both males and females (<a href="#15" class="mim-tip-reference" title="Donabedian, H., Gallin, J. I. <strong>The hyperimmunoglobulin E recurrent-infection (Job's) syndrome: a review of the NIH experience and the literature.</strong> Medicine 62: 195-208, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6348470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6348470</a>] [<a href="https://doi.org/10.1097/00005792-198307000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6348470">Donabedian and Gallin, 1983</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4161105+6348470" 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="Bannatyne, R. M., Skowron, P. N., Weber, J. L. <strong>Job's syndrome, a variant of chronic granulomatous disease.</strong> J. Pediat. 75: 236-242, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5815897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5815897</a>] [<a href="https://doi.org/10.1016/s0022-3476(69)80394-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5815897">Bannatyne et al. (1969)</a> described 2 affected sisters whose parents were second cousins. Despite the fact that their parents were dark-skinned and dark-haired southern Italian immigrants, the proband had red hair, fair skin, and reddish-brown eyes. A sister was clinically well, but had red hair and a mild leukocyte defect demonstrated in vitro. <a href="#15" class="mim-tip-reference" title="Donabedian, H., Gallin, J. I. <strong>The hyperimmunoglobulin E recurrent-infection (Job's) syndrome: a review of the NIH experience and the literature.</strong> Medicine 62: 195-208, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6348470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6348470</a>] [<a href="https://doi.org/10.1097/00005792-198307000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6348470">Donabedian and Gallin (1983)</a> concluded that the patients reported by <a href="#2" class="mim-tip-reference" title="Bannatyne, R. M., Skowron, P. N., Weber, J. L. <strong>Job's syndrome, a variant of chronic granulomatous disease.</strong> J. Pediat. 75: 236-242, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5815897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5815897</a>] [<a href="https://doi.org/10.1016/s0022-3476(69)80394-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5815897">Bannatyne et al. (1969)</a> likely did not have HIES because neutrophils from those patients were unable to kill Staphylococci. Neutrophils isolated from patients with HIES do not show an inability to kill Staph bacteria. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6348470+5815897" 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="#42" class="mim-tip-reference" title="Witemeyer, S., Van Epps, D. E. <strong>A familial defect in cellular chemotaxis associated with redheadedness and recurrent infection.</strong> J. Pediat. 89: 33-37, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/932900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">932900</a>] [<a href="https://doi.org/10.1016/s0022-3476(76)80922-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="932900">Witemeyer and Van Epps (1976)</a> reported a brother and sister with defective cellular chemotaxis, recurrent infection, and red hair. However, neutrophil random mobility and bactericidal activity were normal, suggesting a different disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=932900" 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="#25" class="mim-tip-reference" title="Jung, L. K. L., Engelhard, D., Kapoor, N., Pih, K., Good, R. A. <strong>Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.</strong> Lancet 322: 185-187, 1983. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6135027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6135027</a>] [<a href="https://doi.org/10.1016/s0140-6736(83)90171-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6135027">Jung et al. (1983)</a> identified a familial immunodeficiency disease characterized by recurrent and persistent pyoderma, folliculitis, and atopic dermatitis. An affected father, aged 39 years, and his affected 11-year-old son were studied. The father's father, who had died, was alleged to have had a similar disease in childhood. Abnormalities of lymphocyte function (defective proliferative responses to phytomitogens and subnormal response in immunoglobulin production after stimulation of lymphocytes by pokeweed mitogen) and defective leukocyte chemiluminescence responses were associated with defective intracellular killing of microbial organisms. Chemotaxis was normal. The clinical manifestations and abnormalities of lymphocyte and leukocyte function responded dramatically to treatment with the histamine-1 antagonist chlorpheniramine, suggesting to the authors a defect in histamine metabolism or abnormality of histamine receptors on lymphocytes and leukocytes. The son had corneal ulcerations; the father had had corneal transplants several times for scarring due to herpetic lesions. <a href="#25" class="mim-tip-reference" title="Jung, L. K. L., Engelhard, D., Kapoor, N., Pih, K., Good, R. A. <strong>Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.</strong> Lancet 322: 185-187, 1983. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6135027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6135027</a>] [<a href="https://doi.org/10.1016/s0140-6736(83)90171-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6135027">Jung et al. (1983)</a> pointed out similarities to families reported by <a href="#40" class="mim-tip-reference" title="Van Scoy, R. E., Hill, H. R., Ritts, R. E., Jr., Quie, P. G. <strong>Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.</strong> Ann. Intern. Med. 82: 766-771, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1138587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1138587</a>] [<a href="https://doi.org/10.7326/0003-4819-82-6-766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1138587">Van Scoy et al. (1975)</a>, <a href="#24" class="mim-tip-reference" title="Jacobs, J. C., Norman, M. E. <strong>A familial defect of neutrophil chemotaxis with asthma, eczema, and recurrent skin infections.</strong> Pediat. Res. 11: 732-736, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/865918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">865918</a>] [<a href="https://doi.org/10.1203/00006450-197706000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="865918">Jacobs and Norman (1977)</a>, and <a href="#36" class="mim-tip-reference" title="Robinson, M. F., McGregor, R., Collins, R., Cheung, K. <strong>Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease.</strong> Am. J. Med. 73: 63-70, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6979928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6979928</a>] [<a href="https://doi.org/10.1016/0002-9343(82)90927-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6979928">Robinson et al. (1982)</a>. <a href="#25" class="mim-tip-reference" title="Jung, L. K. L., Engelhard, D., Kapoor, N., Pih, K., Good, R. A. <strong>Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.</strong> Lancet 322: 185-187, 1983. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6135027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6135027</a>] [<a href="https://doi.org/10.1016/s0140-6736(83)90171-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6135027">Jung et al. (1983)</a> also noted that <a href="#32" class="mim-tip-reference" title="Mawhinney, H., Killen, M., Fleming, W. A., Roy, D. A. <strong>The hyper-immunoglobulin E syndrome--a neutrophil chemotactic defect reversible by histamine H2 receptor blockade?</strong> Clin. Immun. Immunopath. 17: 483-491, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6108173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6108173</a>] [<a href="https://doi.org/10.1016/0090-1229(80)90144-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6108173">Mawhinney et al. (1980)</a> had described a patient with hyper-IgE syndrome, recurrent abscesses, and a chemotactic abnormality whose chemotactic defect and clinical disorder improved with treatment with cimetidine, an H2 blocker. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6135027+6979928+1138587+6108173+865918" 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="#Buckley1981" class="mim-tip-reference" title="Buckley, R. H., Sampson, H. A. <strong>The hyperimmunoglobulinemia E syndrome. In: Franklin, E. C.: Clinical Immunology Update.</strong> New York: Elsevier/North Holland Biomedical Press (pub.) 1981. Pp. 148-167.">Buckley and Sampson (1981)</a>; <a href="#Geha1981" class="mim-tip-reference" title="Geha, R. S., Reinherz, E., Leung, D., McKee, K. T., Jr., Schlossman, S., Rosen, F. S. <strong>Deficiency of suppressor T cells in the hyperimmunoglobulin E syndrome.</strong> J. Clin. Invest. 68: 783-791, 1981.">Geha et al. (1981)</a>; <a href="#Leung1986" class="mim-tip-reference" title="Leung, D. Y. M., Frankel, R., Wood, N., Geha, R. S. <strong>Potentiation of human immunoglobulin E synthesis by plasma immunoglobulin E binding factors from patients with the hyperimmunoglobulin E syndrome.</strong> J. Clin. Invest. 77: 952-957, 1986.">Leung et al. (1986)</a>
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<ol>
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<li>
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<a id="1" class="mim-anchor"></a>
|
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<a id="Asano2021" class="mim-anchor"></a>
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Asano, T., Khourieh, J., Zhang, P., Rapaport, F., Spaan, A. N., Li, J., Lei, W.-T., Pelham, S. J., Hum, D., Chrabieh, M., Han, J. E., Guerin, A., and 24 others.
|
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<strong>Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.</strong>
|
|
J. Exp. Med. 218: e20202592, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34137790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34137790</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34137790[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34137790" 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/10.1084/jem.20202592" target="_blank">Full Text</a>]
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<a id="Bannatyne1969" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Bannatyne, R. M., Skowron, P. N., Weber, J. L.
|
|
<strong>Job's syndrome, a variant of chronic granulomatous disease.</strong>
|
|
J. Pediat. 75: 236-242, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5815897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5815897</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5815897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(69)80394-x" target="_blank">Full Text</a>]
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</li>
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<a id="3" class="mim-anchor"></a>
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<a id="Berglund2013" class="mim-anchor"></a>
|
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Berglund, L. J., Avery, D. T., Ma, C. S., Moens, L., Deenick, E. K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P. D., Bacchetta, R., Bezrodnik, L., and 12 others.
|
|
<strong>IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts.</strong>
|
|
Blood 122: 3940-3950, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24159173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24159173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24159173[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24159173" 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/10.1182/blood-2013-06-506865" target="_blank">Full Text</a>]
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|
|
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|
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Blum, R., Geller, G., Fish, L. A.
|
|
<strong>Recurrent severe staphylococcal infections, eczematoid rash: extreme elevations of IgE, eosinophilia and different chemotactic responses in two generations.</strong>
|
|
J. Pediat. 90: 607-609, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/839376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">839376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=839376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(77)80380-6" target="_blank">Full Text</a>]
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
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|
<a id="Borges1998" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Borges, W. G., Hensley, T., Carey, J. C., Petrak, B. A., Hill, H. R.
|
|
<strong>The face of Job.</strong>
|
|
J. Pediat. 133: 303-305, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709729</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709729" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(98)70243-4" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
|
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<a id="6" class="mim-anchor"></a>
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<a id="Brestel1982" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Brestel, E. P., Klingberg, W. G., Veltri, R. W., Dorn, J. S.
|
|
<strong>Osteogenesis imperfecta tarda in a child with hyper IgE syndrome.</strong>
|
|
Am. J. Dis. Child. 136: 774-776, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6981344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6981344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6981344" 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/10.1001/archpedi.1982.03970450016003" target="_blank">Full Text</a>]
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<li>
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<a id="7" class="mim-anchor"></a>
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|
|
<div class="">
|
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<p class="mim-text-font">
|
|
Buckley, R. H., Becker, W. G.
|
|
<strong>Abnormalities in the regulation of human IgE synthesis.</strong>
|
|
Immun. Rev. 41: 288-314, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/360511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">360511</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=360511" 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.1600-065x.1978.tb01469.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Buckley1981" class="mim-anchor"></a>
|
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<div class="">
|
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Buckley, R. H., Sampson, H. A.
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<strong>The hyperimmunoglobulinemia E syndrome. In: Franklin, E. C.: Clinical Immunology Update.</strong>
|
|
New York: Elsevier/North Holland Biomedical Press (pub.) 1981. Pp. 148-167.
|
|
|
|
|
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</p>
|
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</div>
|
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</li>
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<li>
|
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<a id="9" class="mim-anchor"></a>
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<a id="Buckley1972" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
|
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Buckley, R. H., Wray, B. B., Belmaker, E. Z.
|
|
<strong>Extreme hyperimmunoglobulin E and undue susceptibility to infection.</strong>
|
|
Pediatrics 49: 59-70, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5059313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5059313</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5059313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Crosby2012" class="mim-anchor"></a>
|
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|
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Crosby, K., Swender, D., Chernin, L., Hafez-Khayyata, S., Ochs, H., Tcheurekdjian, H., Hostoffer, R.
|
|
<strong>Signal transducer and activator of transcription 3 mutation with invasive eosinophilic disease.</strong>
|
|
Allergy Rhinol. (Providence) 3: e94-e97, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23342295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23342295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23342295[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23342295" 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/10.2500/ar.2012.3.0035" target="_blank">Full Text</a>]
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</div>
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<a id="Davis1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davis, S. D., Schaller, J., Wedgwood, R. J.
|
|
<strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong>
|
|
Lancet 287: 1013-1015, 1966. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4161105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4161105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4161105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(66)90119-x" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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|
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de Beaucoudrey, L., Puel, A., Filipe-Santos, O., Cobat, A., Ghandil, P., Chrabieh, M., Feinberg, J., von Bernuth, H., Samarina, A., Janniere, L., Fieschi, C., Stephan, J.-L., Boileau, C., and 33 others.
|
|
<strong>Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.</strong>
|
|
J. Exp. Med. 205: 1543-1550, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18591412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18591412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18591412[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18591412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20080321" target="_blank">Full Text</a>]
|
|
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|
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|
|
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|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Donabedian1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donabedian, H., Alling, D. W., Gallin, J. I.
|
|
<strong>Levamisole is inferior to placebo in the hyperimmunoglobulin E recurrent-infection (Job's) syndrome.</strong>
|
|
New Eng. J. Med. 307: 290-292, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6806658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6806658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6806658" 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/NEJM198207293070506" target="_blank">Full Text</a>]
|
|
|
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|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Donabedian1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donabedian, H., Gallin, J. I.
|
|
<strong>Mononuclear cells from patients with the hyperimmunoglobulin E-recurrent-infection syndrome produce an inhibitor of leukocyte chemotaxis.</strong>
|
|
J. Clin. Invest. 69: 1155-1163, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7068851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7068851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7068851" 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/jci110551" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Donabedian1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donabedian, H., Gallin, J. I.
|
|
<strong>The hyperimmunoglobulin E recurrent-infection (Job's) syndrome: a review of the NIH experience and the literature.</strong>
|
|
Medicine 62: 195-208, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6348470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6348470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6348470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00005792-198307000-00001" target="_blank">Full Text</a>]
|
|
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|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Dreskin1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dreskin, S. C., Goldsmith, P. K., Gallin, J. I.
|
|
<strong>Immunoglobulins in the hyperimmunoglobulin E and recurrent infection (Job's) syndrome: deficiency of anti-Staphylococcus aureus immunoglobulin A.</strong>
|
|
J. Clin. Invest. 75: 26-34, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3871199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3871199</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3871199" 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/JCI111683" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Geha1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Geha, R. S., Reinherz, E., Leung, D., McKee, K. T., Jr., Schlossman, S., Rosen, F. S.
|
|
<strong>Deficiency of suppressor T cells in the hyperimmunoglobulin E syndrome.</strong>
|
|
J. Clin. Invest. 68: 783-791, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6456275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6456275</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6456275" 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/jci110315" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Grimbacher1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M.
|
|
<strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong>
|
|
New Eng. J. Med. 340: 692-702, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10053178" 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/NEJM199903043400904" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Grimbacher1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grimbacher, B., Schaffer, A. A., Holland, S. M., Davis, J., Gallin, J. I., Malech, H. L., Atkinson, T. P., Belohradsky, B. H., Buckley, R. H., Cossu, F., Espanol, T., Garty, B.-Z., Matamoros, N., Myers, L. A., Nelson, R. P., Ochs, H. D., Renner, E. D., Wellinghausen, N., Puck, J. M.
|
|
<strong>Genetic linkage of hyper-IgE syndrome to chromosome 4.</strong>
|
|
Am. J. Hum. Genet. 65: 735-744, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302547" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Hill1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hill, H. R., Ochs, H. D., Quie, P. G., Clark, R. A., Pabst, H. F., Klebanoff, S. J., Wedgwood, R. J.
|
|
<strong>Defect in neutrophil granulocyte chemotaxis in Job's syndrome of recurrent 'cold' staphylococcal abscesses.</strong>
|
|
Lancet 304: 617-619, 1974. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4137601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4137601</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4137601" 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/s0140-6736(74)91942-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Hill1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hill, H. R., Quie, P. G.
|
|
<strong>Raised serum-IgE levels and defective neutrophil chemotaxis in three children with eczema and recurrent bacterial infections.</strong>
|
|
Lancet 303: 183-187, 1974. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4129875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4129875</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4129875" 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/s0140-6736(74)92493-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Hoger1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoger, P. H., Boltshauser, E., Hitzig, W. H.
|
|
<strong>Craniosynostosis in hyper-IgE-syndrome.</strong>
|
|
Europ. J. Pediat. 144: 414-417, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4076261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4076261</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4076261" 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/BF00441793" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Holland2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N., Freeman, A. F., Demidowich, A., Davis, J., Turner, M. L., Anderson, V. L., Darnell, D. N., and 13 others.
|
|
<strong>STAT3 mutations in the hyper-IgE syndrome.</strong>
|
|
New Eng. J. Med. 357: 1608-1619, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17881745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17881745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17881745" 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/NEJMoa073687" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Jacobs1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jacobs, J. C., Norman, M. E.
|
|
<strong>A familial defect of neutrophil chemotaxis with asthma, eczema, and recurrent skin infections.</strong>
|
|
Pediat. Res. 11: 732-736, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/865918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">865918</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=865918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-197706000-00007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Jung1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jung, L. K. L., Engelhard, D., Kapoor, N., Pih, K., Good, R. A.
|
|
<strong>Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.</strong>
|
|
Lancet 322: 185-187, 1983. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6135027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6135027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6135027" 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/s0140-6736(83)90171-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Kirchner1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kirchner, S. G., Sivit, C. J., Wright, P. F.
|
|
<strong>Hyperimmunoglobulinemia E syndrome: association with osteoporosis and recurrent fractures.</strong>
|
|
Radiology 156: 362 only, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4011897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4011897</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4011897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1148/radiology.156.2.4011897" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Leung1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leung, D. Y. M., Frankel, R., Wood, N., Geha, R. S.
|
|
<strong>Potentiation of human immunoglobulin E synthesis by plasma immunoglobulin E binding factors from patients with the hyperimmunoglobulin E syndrome.</strong>
|
|
J. Clin. Invest. 77: 952-957, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3485112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3485112</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3485112" 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/JCI112395" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Leung1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leung, D. Y. M., Geha, R. S.
|
|
<strong>Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome.</strong>
|
|
Hemat. Oncol. Clin. North Am. 2: 81-100, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3279022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3279022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3279022" 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="Lui1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lui, R. C., Inculet, R. I.
|
|
<strong>Job's syndrome: a rare cause of recurrent lung abscess in childhood.</strong>
|
|
Ann. Thorac. Surg. 50: 992-994, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2241394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2241394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2241394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0003-4975(90)91144-z" target="_blank">Full Text</a>]
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<a id="30" class="mim-anchor"></a>
|
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<a id="Lyons2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Lyons, J. J., Liu, Y., Ma, C. A., Yu, X., O'Connell, M. P., Lawrence, M. G., Zhang, Y., Karpe, K., Zhao, M., Siegel, A. M., Stone, K. D., Nelson, C., and 13 others.
|
|
<strong>ERBIN deficiency links STAT3 and TGF-beta pathway defects with atopy in humans.</strong>
|
|
J. Exp. Med. 214: 669-680, 2017. Note: Erratum: J. Exp. Med. 214: 1201 only, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28126831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28126831</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28126831[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28126831" 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/10.1084/jem.20161435" target="_blank">Full Text</a>]
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|
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<a id="Ma2008" class="mim-anchor"></a>
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|
|
Ma, C. S., Chew, G. Y. J., Simpson, N., Priyadarshi, A., Wong, M., Grimbacher, B., Fulcher, D. A., Tangye, S. G., Cook, M. C.
|
|
<strong>Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3.</strong>
|
|
J. Exp. Med. 205: 1551-1557, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18591410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18591410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18591410[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18591410" 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/10.1084/jem.20080218" target="_blank">Full Text</a>]
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<a id="32" class="mim-anchor"></a>
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<a id="Mawhinney1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mawhinney, H., Killen, M., Fleming, W. A., Roy, D. A.
|
|
<strong>The hyper-immunoglobulin E syndrome--a neutrophil chemotactic defect reversible by histamine H2 receptor blockade?</strong>
|
|
Clin. Immun. Immunopath. 17: 483-491, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6108173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6108173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6108173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1016/0090-1229(80)90144-0" target="_blank">Full Text</a>]
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|
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|
|
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|
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<a id="33" class="mim-anchor"></a>
|
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<a id="Milner2008" class="mim-anchor"></a>
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<div class="">
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|
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Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., Davis, J., Hsu, A., Asher, A. I., O'Shea, J., Holland, S. M., Paul, W. E., Douek, D. C.
|
|
<strong>Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome.</strong>
|
|
Nature 452: 773-776, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337720</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337720[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature06764" target="_blank">Full Text</a>]
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|
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|
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<a id="34" class="mim-anchor"></a>
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<a id="Minegishi2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Minegishi, Y., Saito, M., Tsuchiya, S., Tsuge, I., Takada, H., Hara, T., Kawamura, N., Ariga, T., Pasic, S., Stojkovic, O., Metin, A., Karasuyama, H.
|
|
<strong>Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.</strong>
|
|
Nature 448: 1058-1062, 2007.
|
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17676033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17676033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17676033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature06096" target="_blank">Full Text</a>]
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|
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<a id="35" class="mim-anchor"></a>
|
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<a id="Renner2007" class="mim-anchor"></a>
|
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|
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|
|
Renner, E. D., Torgerson, T. R., Rylaarsdam, S., Anover-Sombke, S., Golob, K., LaFlam, T., Zhu, Q., Ochs, H. D.
|
|
<strong>STAT3 mutation in the original patient with Job's syndrome. (Letter)</strong>
|
|
New Eng. J. Med. 357: 1667-1668, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17942886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17942886</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17942886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMc076367" target="_blank">Full Text</a>]
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<a id="36" class="mim-anchor"></a>
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<a id="Robinson1982" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
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Robinson, M. F., McGregor, R., Collins, R., Cheung, K.
|
|
<strong>Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease.</strong>
|
|
Am. J. Med. 73: 63-70, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6979928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6979928</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6979928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0002-9343(82)90927-5" target="_blank">Full Text</a>]
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<a id="37" class="mim-anchor"></a>
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<a id="Siegel2011" class="mim-anchor"></a>
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<div class="">
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Siegel, A. M., Heimall, J., Freeman, A. F., Hsu, A. P., Brittain, E., Brenchley, J. M., Douek, D. C., Fahle, G. H., Cohen, J. I., Holland, S. M., Milner, J. D.
|
|
<strong>A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.</strong>
|
|
Immunity 35: 806-818, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22118528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22118528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22118528[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22118528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.immuni.2011.09.016" target="_blank">Full Text</a>]
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<a id="38" class="mim-anchor"></a>
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<a id="Swim1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
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Swim, A. T., Bradac, C., Craddock, P. R.
|
|
<strong>Levamisole in Job's syndrome. (Letter)</strong>
|
|
New Eng. J. Med. 307: 1528-1529, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7144828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7144828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7144828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJM198212093072424" target="_blank">Full Text</a>]
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<a id="39" class="mim-anchor"></a>
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<a id="Urban2022" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urban, A., NCI Lymphoma Physicians Consortium, Pittaluga, S., Case Western Physicians Consortium, Freeman, A. F.
|
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<strong>Malignancy in STAT3 deficient hyper IgE syndrome.</strong>
|
|
J. Clin. Immun. 42: 699-702, 2022. Note: Erratum: J. Clin. Immun. 42: 1348 only, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35059947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35059947</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35059947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10875-021-01197-y" target="_blank">Full Text</a>]
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<a id="Van Scoy1975" class="mim-anchor"></a>
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<div class="">
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Van Scoy, R. E., Hill, H. R., Ritts, R. E., Jr., Quie, P. G.
|
|
<strong>Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.</strong>
|
|
Ann. Intern. Med. 82: 766-771, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1138587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1138587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1138587" 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/10.7326/0003-4819-82-6-766" target="_blank">Full Text</a>]
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White, L. R., Iannetta, A., Kaplan, E. L., Davis, S. D., Wedgwood, R. J.
|
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<strong>Leucocytes in Job's syndrome. (Letter)</strong>
|
|
Lancet 293: 630 only, 1969. Note: Originally Volume 1.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4180157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4180157</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4180157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(69)91577-3" target="_blank">Full Text</a>]
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<a id="Witemeyer1976" class="mim-anchor"></a>
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<div class="">
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Witemeyer, S., Van Epps, D. E.
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<strong>A familial defect in cellular chemotaxis associated with redheadedness and recurrent infection.</strong>
|
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J. Pediat. 89: 33-37, 1976.
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|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/932900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">932900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=932900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(76)80922-5" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/03/2023
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 06/16/2022<br>Cassandra L. Kniffin - updated : 12/13/2021<br>Cassandra L. Kniffin - updated : 07/23/2020<br>Paul J. Converse - updated : 9/19/2014<br>Paul J. Converse - updated : 12/20/2013<br>Paul J. Converse - updated : 9/13/2013<br>Paul J. Converse - updated : 9/24/2012<br>Ada Hamosh - updated : 5/21/2008<br>Victor A. McKusick - updated : 10/22/2007<br>Cassandra L. Kniffin - reorganized : 10/9/2007<br>Cassandra L. Kniffin - updated : 10/9/2007<br>Victor A. McKusick - updated : 9/20/1999<br>Victor A. McKusick - updated : 3/5/1999
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Victor A. McKusick : 6/2/1986
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carol : 10/06/2023
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carol : 10/05/2023<br>ckniffin : 10/03/2023<br>joanna : 08/29/2023<br>carol : 01/21/2023<br>carol : 06/17/2022<br>carol : 06/16/2022<br>alopez : 02/23/2022<br>ckniffin : 02/17/2022<br>alopez : 12/17/2021<br>ckniffin : 12/13/2021<br>carol : 08/05/2020<br>carol : 07/29/2020<br>carol : 07/28/2020<br>ckniffin : 07/23/2020<br>alopez : 07/21/2020<br>ckniffin : 07/12/2020<br>carol : 07/31/2019<br>ckniffin : 07/29/2019<br>alopez : 01/16/2019<br>ckniffin : 01/15/2019<br>carol : 12/21/2018<br>carol : 12/20/2018<br>carol : 07/08/2016<br>carol : 7/7/2016<br>mgross : 10/2/2014<br>mgross : 10/2/2014<br>mcolton : 9/19/2014<br>mgross : 12/20/2013<br>mcolton : 12/12/2013<br>carol : 11/6/2013<br>mgross : 9/13/2013<br>mgross : 9/13/2013<br>carol : 8/6/2013<br>mgross : 10/4/2012<br>terry : 9/24/2012<br>alopez : 1/7/2010<br>wwang : 11/30/2009<br>terry : 4/29/2009<br>terry : 4/8/2009<br>terry : 2/3/2009<br>alopez : 5/28/2008<br>alopez : 5/28/2008<br>terry : 5/21/2008<br>carol : 3/19/2008<br>ckniffin : 10/26/2007<br>carol : 10/24/2007<br>carol : 10/23/2007<br>terry : 10/22/2007<br>carol : 10/9/2007<br>ckniffin : 10/9/2007<br>mgross : 3/17/2004<br>carol : 3/14/2000<br>terry : 3/14/2000<br>jlewis : 9/29/1999<br>terry : 9/20/1999<br>carol : 3/5/1999<br>terry : 3/5/1999<br>mimadm : 11/5/1994<br>carol : 5/16/1994<br>terry : 1/26/1994<br>carol : 4/27/1992<br>supermim : 3/16/1992<br>supermim : 3/20/1990
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<strong>#</strong> 147060
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HYPER-IgE SYNDROME 1, AUTOSOMAL DOMINANT, WITH RECURRENT INFECTIONS; HIES1
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HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT<br />
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HYPER-IgE SYNDROME, AUTOSOMAL DOMINANT<br />
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HIES, AUTOSOMAL DOMINANT<br />
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JOB SYNDROME
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<strong>SNOMEDCT:</strong> 50926003;
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<strong>ICD10CM:</strong> D82.4;
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<strong>ORPHA:</strong> 2314;
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<strong>DO:</strong> 3261;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus <br /> MIM number
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17q21.2
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Hyper-IgE syndrome 1, autosomal dominant, with recurrent infections
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147060
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Autosomal dominant
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3
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STAT3
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102582
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant hyper-IgE syndrome-1 with recurrent infections (HIES1) is caused by heterozygous mutation in the STAT3 gene (102582) on chromosome 17q21. The mutations cause a dominant-negative effect.</p><p>Heterozygous gain-of-function mutations in the STAT3 gene cause an infantile-onset multisystem autoimmune disease (ADMIO1; 615952).</p>
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<strong>Description</strong>
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<p>Hyper-IgE syndrome-1 with recurrent infections (HIES1) is an autosomal dominant immunologic disorder characterized by chronic eczema (atopy), recurrent Staphylococcal infections, increased serum IgE, and eosinophilia. Other more variable immunologic abnormalities include defective granulocyte chemotaxis, abnormalities in T-lymphocyte subgroups, impaired antibody production, and decreased production of or response to certain cytokines. Importantly, the same immune system defects are not found in all patients. Some patients may have a distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures (Buckley et al., 1972; Grimbacher et al., 1999). </p><p><strong><em>Genetic Heterogeneity of Hyper-IgE Syndrome</em></strong></p><p>
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See also HIES2 (243700), caused by mutation in the DOCK8 gene (611432); HIES3 (618282), caused by mutation in the ZNF341 gene (618269); HIES4A (619752) and HIES4B (618523), both caused by mutation in the IL6ST gene (600694); HIES5 (618944), caused by mutation in the IL6R gene (147880); and HIES6 (620532), caused by mutation in the STAT6 gene (601512).</p>
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<strong>Clinical Features</strong>
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<p>Davis et al. (1966) reported 2 unrelated girls with lifelong histories of indolent Staphylococcal abscesses. Both had eczema soon after birth and had persistent weeping lesions on the ears and face. The abscesses were characterized as 'cold' because of the lack of surrounding warmth, erythema, or tenderness. Both girls had red hair and were fair-skinned. The authors suggested a defect in local resistance to Staphylococcal infection. Further study of these girls by White et al. (1969) revealed normal leukocyte functions. However, Hill et al. (1974) and Hill and Quie (1974) found a defect in neutrophil granulocyte chemotaxis and very high serum IgE levels in 4 girls with the disorder; 2 of the girls had been reported by Davis et al. (1966). </p><p>Renner et al. (2007) provided a follow-up of 1 of the patients reported by Davis et al. (1966). At 50 years of age, the woman had had lifelong eczema, multiple atraumatic fractures, hyperkeratotic fingernails due to candida infection, recurrent Staphylococcal abscesses, and pneumonia with lung abscesses and pneumatocele formation. Two of her 3 sons and 1 grandson were also affected. </p><p>Buckley et al. (1972) described 2 male patients with features of Job syndrome as originally described by Davis et al. (1966). Each boy had extremely high serum IgE levels as well as immediate cutaneous hypersensitivity reactions to Staphylococcus aureus and Candida albicans. The authors also noted joint hyperextensibility and asymmetric facies. </p><p>Van Scoy et al. (1975) described a 20-year-old woman and her daughter who had recurrent bacterial infections and chronic mucocutaneous candidiasis. Laboratory studies showed marked elevation of serum IgE, defective neutrophil chemotaxis, and impaired lymphocyte response to candida antigen. The mother's brother, father, and paternal grandfather showed mild increases in IgE and mildly depressed chemotactic activity of neutrophils. </p><p>Jacobs and Norman (1977) found a cellular chemotactic defect in the neutrophils of both parents and 3 of 4 their children who suffered from unusually severe bacterial eczema, asthma, and recurrent bacterial skin infections, all starting in the first month of life. The parents were less severely affected. Those with severe eczema had increased IgE. All affected members had HLA-B12; the unaffected child did not. The 2 most severely affected children were homozygous for HLA-B12. </p><p>Osteoporosis and a propensity to bone fracture, referred to by Brestel et al. (1982) as 'osteogenesis imperfecta tarda,' was a recognized feature of hyper-IgE syndrome. Kirchner et al. (1985) also noted the association of hyper-IgE syndrome with osteoporosis and recurrent fractures. Hoger et al. (1985) described the association with craniosynostosis and discussed 3 reported cases. </p><p>Robinson et al. (1982) described a kindred brought to attention because of a 6-year-old girl who showed features of both the hyper-IgE syndrome and chronic granulomatous disease. Inheritance was possibly autosomal dominant. Laboratory studies showed impaired T cell responses. </p><p>Donabedian and Gallin (1982) presented evidence suggesting that mononuclear cells from patients with the hyper-IgE recurrent infection syndrome produced an inhibitor of leukocyte chemotaxis. </p><p>Donabedian and Gallin (1983) provided a review of 13 patients with hyper-IgE syndrome examined at the National Institutes of Health. Nine of the 13 had coarse facies, with broad nasal bridge, prominent nose, and irregularly proportioned cheeks and jaws. All had recurrent skin infections, most by 3 months of age. All patients, except 1, had recurrent pneumonias, and most had recurrent bronchitis and otitis. Many patients developed pneumatoceles and most required chest tube drainage and/or lobectomies. Seven of the 13 had Candidal infections of the nails, vagina, or mouth. Three additional patients were described as having a 'variant' of the disorder due to lack of cold abscesses and serious sinopulmonary infection, declining serum IgE levels, and first appearance of infection at age 17 years, respectively. Laboratory studies showed mild to moderate eosinophilia. Impaired neutrophil chemotaxis was not a constant feature, and it was not severe when it occurred. There was some evidence for a chemotactic inhibitor. </p><p>In patients with hyper-IgE syndrome, Dreskin et al. (1985) demonstrated deficiency of serum anti-Staph aureus IgA, salivary IgA, and salivary anti-Staph aureus IgA. There was an inverse correlation between the number of infections at mucosal surfaces and in adjacent lymph nodes and the levels of these substances as well as of total serum IgE and total serum IgD. </p><p>Lui and Inculet (1990) described a patient with presumed Job syndrome and recurrent lung abscess necessitating lung resection. Serum IgE levels were markedly elevated. Some of the lung abscesses appeared to be due to Staph aureus; the resected right lower lobe showed an abscess cavity with aspergilloma. </p><p>Borges et al. (1998) evaluated the facial features of 9 patients from 7 kindreds with Job syndrome. Consistent features included prominent forehead with deep-set eyes, increased width of the nose, a full lower lip, and thickening of the nose and ears. The mean alar width and outer canthal distance were significantly increased. The authors concluded that there is a recognizable face of Job syndrome. </p><p>The study of Grimbacher et al. (1999) established that the hyper-IgE syndrome is a multisystem disorder. Grimbacher et al. (1999) studied 30 patients with hyper-IgE syndrome and 70 of their relatives. In addition to the recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum, there are associated facial, dental, and skeletal features. Nonimmunologic features of the hyper-IgE syndrome were present in all patients older than 8 years. Failure or delay of shedding of the primary teeth owing to lack of root resorption was observed in 72%. Common findings among patients were recurrent fractures (57%), hyperextensible joints (68%), and scoliosis (in 76% of patients over 16 years of age). The classic triad of abscesses, pneumonia, and an elevated IgE level was identified in 77% of all patients and in 85% of those older than 8 years. In 6 (26%) of 23 adults, IgE levels declined over time and came closer to or fell within the normal range. </p><p>Grimbacher et al. (1999) noted the unusual facial phenotype of the hyper-IgE syndrome, which had been commented on by Davis et al. (1966) and by Borges et al. (1998). By the age of 16 years, all of the patients studied by Grimbacher et al. (1999) showed distinctive facial characteristics, including facial asymmetry with a suggestion of hemihypertrophy, prominent forehead, deep-set eyes, broad nasal bridge, wide, fleshy nasal tip, and mild prognathism. The facial skin was rough, with prominent pores. The interalar distance was increased. Head circumference also tended to be larger than normal. </p><p>Crosby et al. (2012) reported a 35-year-old African-American male who presented with dysphagia that was resistant to proton pump inhibitors. The patient had a normal blood cell count and differential with 12% eosinophils and total IgE of 2728 kU/L. Additional complaints included constipation with soy and hives after eating fish. The patient had a history of recurrent infections, including staphylococcal pneumonia, as well as skin abscesses, fractures, and esophageal candidiasis. He had undergone left lung pneumonectomy secondary to pneumatocele formation after severe pneumonia. The patient had coarse facies, broad nasal bridge, moderate eczema, and hyperextensibility, and his HIES score was 53. He was found to have a ringed esophagus. Histopathologic analysis of the middle third of the esophagus revealed elevated eosinophil numbers. </p><p>Asano et al. (2021) reported 10 patients from 7 unrelated families with HIES1 confirmed by genetic analysis. The patients, who ranged from childhood to middle age, had typical features of the disorder, including recurrent sinopulmonary infections due to bacteria and fungus, variable inflammatory skin disease, bronchiectasis, increased serum IgE, and increased eosinophils. A few patients had atypical features of the disorder, such as tuberculosis or only slightly elevated IgE. Connective tissue abnormalities and dysmorphic facies were not described, although 1 had poor overall growth and another had osteopenia. </p><p>In a retrospective review of the histories of 158 patients with HIES1 with dominant-negative mutations in the STAT3 gene (STAT3DN) who were enrolled in a large natural history study, Urban et al. (2022) identified 13 malignancies in 11 patients, giving an incidence of 8.2%. The median age of the full cohort was 25 years. The age at cancer diagnosis ranged from 4 to 65 years. Among the 13 malignancies, 8 were non-Hodgkin lymphomas (NHL) (5.1%), 2 were thyroid carcinomas (1.3%), and 3 were nonmelanoma skin cancers (1.9%). One patient had both a papillary thyroid cancer and NHL, and 1 patient had 2 types of skin cancers (basal cell and squamous cell carcinomas). All patients tolerated their cancer treatments and had achieved full remission. Urban et al. (2022) emphasized the importance of monitoring patients with HIES1 for cancer, with consideration of a cancer diagnosis in patients with persistent or progressive lymphadenopathy or thyroid nodules. </p>
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<strong>Pathogenesis</strong>
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<p>Milner et al. (2008) showed that interleukin-17 (IL17; see 603149) production by T cells is absent in individuals with hyper-IgE syndrome (HIES). They observed that ex vivo T cells from subjects with HIES failed to produce IL17, but not IL2 (147680), TNF (191160), or IFNG (147570), on mitogenic stimulation with staphylococcal enterotoxin B or on antigenic stimulation with Candida albicans or streptokinase. Purified naive T cells were unable to differentiate into IL17-producing (TH17) T helper cells in vitro and had lower expression of retinoid-related orphan receptor (ROR)-gamma-t (602943), which is consistent with a crucial role for STAT3 (102582) signaling in the generation of TH17 cells. TH17 cells are an important subset of helper T cells that are believed to be critical in the clearance of fungal and extracellular bacterial infections. Thus, Milner et al. (2008) concluded that the inability to produce TH17 cells is a mechanism underlying the susceptibility to recurrent infections commonly seen in HIES. </p><p>Independently, Ma et al. (2008) and de Beaucoudrey et al. (2008) presented findings similar to those of Milner et al. (2008). </p><p>Using flow cytometric analysis, Siegel et al. (2011) demonstrated a significant reduction in central memory (i.e., expressing CD27, 186711, and CD45RO, 151460) CD4 (186940)-positive and CD8 (see 186910)-positive T cells in autosomal dominant HIES patients that was not due to apoptosis or cell turnover. Stimulation of naive T cells in the presence of IL7 (146660) or IL15 (600554) failed to restore memory cell generation in HIES patients. Impaired differentiation was associated with decreased expression of 2 STAT3-responsive transcription factors, BCL6 (109565) and SOCS3 (604176). Siegel et al. (2011) found that HIES patients had increased risk for reactivation of varicella zoster that was associated with poor CD4-positive T-cell responses. HIES patients also had greater detectable Epstein-Barr virus (EBV) viremia that was associated with compromised T-cell memory to EBV. Siegel et al. (2011) concluded that STAT3 has a specific role in central memory T-cell formation. </p><p>Berglund et al. (2013) noted that a feature of autosomal dominant HIES due to STAT3 deficiency is impaired humoral immunity following infection and vaccination. Using microarray analysis, they analyzed STAT3-deficient and normal human naive B cells after stimulation with CD40L (TNFSF5; 300386) alone or with IL21 (605384). The authors observed upregulation of IL2RA (147730) and IL10 (124092) production in normal cells, but not STAT3-deficient cells. IL2 enhanced differentiation of plasma cells and Ig secretion from IL21-stimulated naive B cells. Berglund et al. (2013) concluded that IL21, via STAT3, sensitizes B cells to the stimulatory effects of IL2, which may play an active role in IL21-induced B-cell differentiation. They proposed that lack of this secondary effect of IL21 may amplify humoral immunodeficiency in patients with mutations in STAT3, IL2RG (308380), or IL21R (605383) due to impaired IL21 responsiveness. </p><p>Lyons et al. (2017) found that dominant-negative STAT3 mutations abolished the suppressive effect of the STAT3/ERBIN (606944)/SMAD2/SMAD3 complex on TGF-beta (TGFB; 190180) signaling in vitro. Dominant-negative STAT3 mutations reduced ERBIN expression, which was associated with increased nuclear localization of SMAD2/SMAD3. Loss of ERBIN expression or presence of dominant-negative STAT3 variants in patient CD4+ T cells resulted in increased FOXP3 (300292) expression with increased levels of Treg cells that was dose-dependent on TGF-beta levels. SMAD3 activation and STAT3 knockdown also potentiated the transcriptional activity of GATA3 (131320), the canonical Th2 transcription factor, and induced expression of IL4R (147781). Lymphocytes from patients with dominant-negative STAT3 mutations and from individuals with decreased ERBIN expression had increased IL4R levels and increased STAT6 phosphorylation and activation in response to IL4 (147780), ultimately promoting B-cell development and activation, class switching to IgE, and differentiation of Th2 cells through increased GATA3 expression. Inhibition of SMAD3, TGFBR1 (190181), or IL4 normalized GATA3 expression in mutant lymphocytes, and the authors suggested that IL4R blockade would also be effective in reducing TGF-beta signaling. The findings linked increased TGF-beta pathway activation in both ERBIN-deficient and STAT3 mutant lymphocytes, resulting in increased Th2 cytokine expression and elevated IgE, which contribute to immune dysregulation and the atopic/allergic phenotypes. </p>
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<strong>Inheritance</strong>
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<p>Blum et al. (1977) reported hyper-IgE syndrome with recurrent severe Staphylococcal infections, eczematoid rash, and eosinophilia in 2 successive generations of a family. </p><p>Buckley and Becker (1978) reviewed 20 patients with HIE syndrome. Since both males and females were affected in successive generations, they suggested autosomal dominant inheritance with incomplete penetrance. </p><p>Leung and Geha (1988) reported 9 patients with the disorder. None of the patients had a family history of recurrent infections or consanguinity, indicating de novo or sporadic occurrence. </p><p>Grimbacher et al. (1999) concluded that the hyper-IgE syndrome is inherited as an autosomal dominant disorder with variable expressivity. They presented pedigrees of 6 families, 4 of which had definitely affected cases in 2 successive generations. One family had affected father and son. Of 27 relatives at risk for inheriting the disorder, 10 were fully affected, 11 were unaffected, and 6 had combinations of mild immunologic, dental, and skeletal features of the hyper-IgE syndrome. </p>
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<p>Leung and Geha (1988) reviewed cases of HIE syndrome and concluded that the most distinctive feature of the disorder is elevated serum IgE levels. They also emphasized the necessity to distinguish the HIE syndrome from atopic dermatitis (see, e.g., 603165), a disorder with which it is frequently confused. </p><p><strong><em>Distinction from Atopic Dermatitis</em></strong></p><p>
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Grimbacher et al. (1999) noted several distinguishing features of HIE syndrome and severe atopic dermatitis. In HIE syndrome, Staphylococcus aureus infections are deep seeded and serious, non-Staph aureus infections are frequent, respiratory allergy is rare, and onset occurs between 1 and 8 weeks. In atopic dermatitis, Staphylococcus aureus infections are superficial and involve only the skin, non-Staph aureus infections are rare, respiratory allergy is common, and onset occurs after age 2 months. Patients with HIE often have coarse facies, which is not present in patients with atopic dermatitis. Severe atopic dermatitis is at least 10 times more common than HIE. </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>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a prospective trial of levamisole in a large group of patients with Job syndrome, Donabedian et al. (1982) found no decrease in the propensity to infection, despite the fact that the drug clearly reversed the chemotactic defect. In a response to this report, Swim et al. (1982) suggested that the leukocyte defect and the proneness to infection in Job syndrome may be unrelated. </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>HIES1 is caused by mutation in the STAT3 gene, which maps to chromosome 17q21.</p><p><strong><em>Genetic Heterogeneity</em></strong></p><p>
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Grimbacher et al. (1999) scored 19 kindreds with multiple cases of HIES for clinical and laboratory findings and genotyped the members of these 19 kindreds with polymorphic markers in a candidate region on chromosome 4. This region was selected because 1 patient with sporadic HIES plus autism and mental retardation was found to have a supernumerary marker chromosome, derived from a 15- to 20-cM interstitial deletion in 4q21. Linkage analysis in the 19 kindreds showed a maximum 2-point lod score of 3.61 at a recombination fraction of 0.0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES. Six kindreds did not show linkage to 4q, indicating genetic heterogeneity. </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>Minegishi et al. (2007) found that 8 of 15 unrelated nonfamilial HIES patients had heterozygous mutations in the STAT3 gene (see, e.g., 102582.0001-102582.0003). None of the parents or sibs of the patients had the mutant STAT3 allele, suggesting that these were de novo mutations. All 5 identified mutations were located in the DNA-binding domain of STAT3. The peripheral blood cells showed defective responses to cytokines, including interleukin-6 (IL6; 147620) and IL10, and the DNA-binding ability of STAT3 in these cells was greatly diminished. All 5 mutants were nonfunctional by themselves and showed dominant-negative effects when coexpressed with wildtype STAT3. </p><p>Holland et al. (2007) collected longitudinal clinical data on patients with the hyper-IgE syndrome and their families and assayed the levels of cytokine secreted by stimulated leukocytes and the gene expression in resting and stimulated cells. These data implicated STAT3 as a candidate gene, which they then sequenced. They identified missense mutations and single-codon in-frame deletions in STAT3 in 50 familial and sporadic cases of the hyper-IgE syndrome. Eighteen discrete mutations, 5 of which were hotspots, were predicted to affect directly the DNA-binding and SRC homology-2 (SH2) domains (see, e.g., 102582.0001-102582.0006). </p><p>Renner et al. (2007) demonstrated that one of the original patients with Job syndrome described by Davis et al. (1966) had a heterozygous arg382-to-trp mutation (R382W; 102582.0002) in the STAT3 gene. </p><p>In the patient they reported with food allergies, a high score for HIES, and eosinophilic esophagitis, Crosby et al. (2012) identified a thr389-to-ile (T389I; 102582.0007) mutation in the STAT3 gene. </p><p>In 10 patients from 7 unrelated families with HIES1, Asano et al. (2021) identified heterozygous nonsense or frameshift mutations in the STAT3 gene. The patients were ascertained from several large cohorts of patients with immune disorders, and the mutations were found by exome sequencing. Detailed in vitro functional expression studies of 150 STAT3 mutations that had been identified in patients with autosomal dominant HIES1 showed that most of the canonical transcripts (95.3%) of these variants encoded STAT3 proteins with little or no STAT3 activity. Fifteen variants were putative loss-of-function alleles. Many of the variants were found to encode truncated proteins that were expressed, produced neoproteins from translation reinitiation codons, or generated isoforms from alternative transcripts. Functional studies using a luciferase assay indicated that autosomal dominant HEIS1 due to STAT3 deficiency is caused by a dominant-negative effect rather than haploinsufficiency. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
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For discussion of a possible association between autosomal dominant hyper-IgE syndrome and variation in the ERBIN gene, see 606944.0001.</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>Nomenclature</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>Davis et al. (1966) called the disorder 'Job syndrome' because of phenotypic similarity to the biblical figure Job: 'Satan...smote Job with sore boils from the sole of his foot unto his crown' (Job 2:7). </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>History</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>The first description of hyper-IgE syndrome (Davis et al., 1966) in girls with fair skin and red hair suggested an association with pigmentation. Later studies showed that the disorder is not associated with red hair or fair skin and that it occurs in both males and females (Donabedian and Gallin, 1983). </p><p>Bannatyne et al. (1969) described 2 affected sisters whose parents were second cousins. Despite the fact that their parents were dark-skinned and dark-haired southern Italian immigrants, the proband had red hair, fair skin, and reddish-brown eyes. A sister was clinically well, but had red hair and a mild leukocyte defect demonstrated in vitro. Donabedian and Gallin (1983) concluded that the patients reported by Bannatyne et al. (1969) likely did not have HIES because neutrophils from those patients were unable to kill Staphylococci. Neutrophils isolated from patients with HIES do not show an inability to kill Staph bacteria. </p><p>Witemeyer and Van Epps (1976) reported a brother and sister with defective cellular chemotaxis, recurrent infection, and red hair. However, neutrophil random mobility and bactericidal activity were normal, suggesting a different disorder. </p><p>Jung et al. (1983) identified a familial immunodeficiency disease characterized by recurrent and persistent pyoderma, folliculitis, and atopic dermatitis. An affected father, aged 39 years, and his affected 11-year-old son were studied. The father's father, who had died, was alleged to have had a similar disease in childhood. Abnormalities of lymphocyte function (defective proliferative responses to phytomitogens and subnormal response in immunoglobulin production after stimulation of lymphocytes by pokeweed mitogen) and defective leukocyte chemiluminescence responses were associated with defective intracellular killing of microbial organisms. Chemotaxis was normal. The clinical manifestations and abnormalities of lymphocyte and leukocyte function responded dramatically to treatment with the histamine-1 antagonist chlorpheniramine, suggesting to the authors a defect in histamine metabolism or abnormality of histamine receptors on lymphocytes and leukocytes. The son had corneal ulcerations; the father had had corneal transplants several times for scarring due to herpetic lesions. Jung et al. (1983) pointed out similarities to families reported by Van Scoy et al. (1975), Jacobs and Norman (1977), and Robinson et al. (1982). Jung et al. (1983) also noted that Mawhinney et al. (1980) had described a patient with hyper-IgE syndrome, recurrent abscesses, and a chemotactic abnormality whose chemotactic defect and clinical disorder improved with treatment with cimetidine, an H2 blocker. </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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Buckley and Sampson (1981); Geha et al. (1981); Leung et al. (1986)
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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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Asano, T., Khourieh, J., Zhang, P., Rapaport, F., Spaan, A. N., Li, J., Lei, W.-T., Pelham, S. J., Hum, D., Chrabieh, M., Han, J. E., Guerin, A., and 24 others.
|
|
<strong>Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.</strong>
|
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J. Exp. Med. 218: e20202592, 2021.
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[PubMed: 34137790]
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[Full Text: https://doi.org/10.1084/jem.20202592]
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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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Bannatyne, R. M., Skowron, P. N., Weber, J. L.
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<strong>Job's syndrome, a variant of chronic granulomatous disease.</strong>
|
|
J. Pediat. 75: 236-242, 1969.
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[PubMed: 5815897]
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|
|
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[Full Text: https://doi.org/10.1016/s0022-3476(69)80394-x]
|
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</p>
|
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</li>
|
|
|
|
<li>
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<p class="mim-text-font">
|
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Berglund, L. J., Avery, D. T., Ma, C. S., Moens, L., Deenick, E. K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P. D., Bacchetta, R., Bezrodnik, L., and 12 others.
|
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<strong>IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts.</strong>
|
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Blood 122: 3940-3950, 2013.
|
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|
|
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[PubMed: 24159173]
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|
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[Full Text: https://doi.org/10.1182/blood-2013-06-506865]
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</p>
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Blum, R., Geller, G., Fish, L. A.
|
|
<strong>Recurrent severe staphylococcal infections, eczematoid rash: extreme elevations of IgE, eosinophilia and different chemotactic responses in two generations.</strong>
|
|
J. Pediat. 90: 607-609, 1977.
|
|
|
|
|
|
[PubMed: 839376]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(77)80380-6]
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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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Borges, W. G., Hensley, T., Carey, J. C., Petrak, B. A., Hill, H. R.
|
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<strong>The face of Job.</strong>
|
|
J. Pediat. 133: 303-305, 1998.
|
|
|
|
|
|
[PubMed: 9709729]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(98)70243-4]
|
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|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Brestel, E. P., Klingberg, W. G., Veltri, R. W., Dorn, J. S.
|
|
<strong>Osteogenesis imperfecta tarda in a child with hyper IgE syndrome.</strong>
|
|
Am. J. Dis. Child. 136: 774-776, 1982.
|
|
|
|
|
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[PubMed: 6981344]
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|
|
|
|
|
[Full Text: https://doi.org/10.1001/archpedi.1982.03970450016003]
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</p>
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Buckley, R. H., Becker, W. G.
|
|
<strong>Abnormalities in the regulation of human IgE synthesis.</strong>
|
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Immun. Rev. 41: 288-314, 1978.
|
|
|
|
|
|
[PubMed: 360511]
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[Full Text: https://doi.org/10.1111/j.1600-065x.1978.tb01469.x]
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</p>
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</li>
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|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Buckley, R. H., Sampson, H. A.
|
|
<strong>The hyperimmunoglobulinemia E syndrome. In: Franklin, E. C.: Clinical Immunology Update.</strong>
|
|
New York: Elsevier/North Holland Biomedical Press (pub.) 1981. Pp. 148-167.
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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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Buckley, R. H., Wray, B. B., Belmaker, E. Z.
|
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<strong>Extreme hyperimmunoglobulin E and undue susceptibility to infection.</strong>
|
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Pediatrics 49: 59-70, 1972.
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|
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|
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[PubMed: 5059313]
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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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Crosby, K., Swender, D., Chernin, L., Hafez-Khayyata, S., Ochs, H., Tcheurekdjian, H., Hostoffer, R.
|
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<strong>Signal transducer and activator of transcription 3 mutation with invasive eosinophilic disease.</strong>
|
|
Allergy Rhinol. (Providence) 3: e94-e97, 2012.
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[PubMed: 23342295]
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[Full Text: https://doi.org/10.2500/ar.2012.3.0035]
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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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Davis, S. D., Schaller, J., Wedgwood, R. J.
|
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<strong>Job's syndrome: recurrent, 'cold,' staphylococcal abscesses.</strong>
|
|
Lancet 287: 1013-1015, 1966. Note: Originally Volume I.
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[PubMed: 4161105]
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[Full Text: https://doi.org/10.1016/s0140-6736(66)90119-x]
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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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de Beaucoudrey, L., Puel, A., Filipe-Santos, O., Cobat, A., Ghandil, P., Chrabieh, M., Feinberg, J., von Bernuth, H., Samarina, A., Janniere, L., Fieschi, C., Stephan, J.-L., Boileau, C., and 33 others.
|
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<strong>Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.</strong>
|
|
J. Exp. Med. 205: 1543-1550, 2008.
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[PubMed: 18591412]
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[Full Text: https://doi.org/10.1084/jem.20080321]
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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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Donabedian, H., Alling, D. W., Gallin, J. I.
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<strong>Levamisole is inferior to placebo in the hyperimmunoglobulin E recurrent-infection (Job's) syndrome.</strong>
|
|
New Eng. J. Med. 307: 290-292, 1982.
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[PubMed: 6806658]
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[Full Text: https://doi.org/10.1056/NEJM198207293070506]
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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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Donabedian, H., Gallin, J. I.
|
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<strong>Mononuclear cells from patients with the hyperimmunoglobulin E-recurrent-infection syndrome produce an inhibitor of leukocyte chemotaxis.</strong>
|
|
J. Clin. Invest. 69: 1155-1163, 1982.
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[PubMed: 7068851]
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[Full Text: https://doi.org/10.1172/jci110551]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Donabedian, H., Gallin, J. I.
|
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<strong>The hyperimmunoglobulin E recurrent-infection (Job's) syndrome: a review of the NIH experience and the literature.</strong>
|
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Medicine 62: 195-208, 1983.
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[PubMed: 6348470]
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[Full Text: https://doi.org/10.1097/00005792-198307000-00001]
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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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Dreskin, S. C., Goldsmith, P. K., Gallin, J. I.
|
|
<strong>Immunoglobulins in the hyperimmunoglobulin E and recurrent infection (Job's) syndrome: deficiency of anti-Staphylococcus aureus immunoglobulin A.</strong>
|
|
J. Clin. Invest. 75: 26-34, 1985.
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[PubMed: 3871199]
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[Full Text: https://doi.org/10.1172/JCI111683]
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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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Geha, R. S., Reinherz, E., Leung, D., McKee, K. T., Jr., Schlossman, S., Rosen, F. S.
|
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<strong>Deficiency of suppressor T cells in the hyperimmunoglobulin E syndrome.</strong>
|
|
J. Clin. Invest. 68: 783-791, 1981.
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[PubMed: 6456275]
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[Full Text: https://doi.org/10.1172/jci110315]
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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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Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C., Puck, J. M.
|
|
<strong>Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.</strong>
|
|
New Eng. J. Med. 340: 692-702, 1999.
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[PubMed: 10053178]
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[Full Text: https://doi.org/10.1056/NEJM199903043400904]
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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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Grimbacher, B., Schaffer, A. A., Holland, S. M., Davis, J., Gallin, J. I., Malech, H. L., Atkinson, T. P., Belohradsky, B. H., Buckley, R. H., Cossu, F., Espanol, T., Garty, B.-Z., Matamoros, N., Myers, L. A., Nelson, R. P., Ochs, H. D., Renner, E. D., Wellinghausen, N., Puck, J. M.
|
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<strong>Genetic linkage of hyper-IgE syndrome to chromosome 4.</strong>
|
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Am. J. Hum. Genet. 65: 735-744, 1999.
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[PubMed: 10441580]
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[Full Text: https://doi.org/10.1086/302547]
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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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Hill, H. R., Ochs, H. D., Quie, P. G., Clark, R. A., Pabst, H. F., Klebanoff, S. J., Wedgwood, R. J.
|
|
<strong>Defect in neutrophil granulocyte chemotaxis in Job's syndrome of recurrent 'cold' staphylococcal abscesses.</strong>
|
|
Lancet 304: 617-619, 1974. Note: Originally Volume 2.
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[PubMed: 4137601]
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[Full Text: https://doi.org/10.1016/s0140-6736(74)91942-4]
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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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Hill, H. R., Quie, P. G.
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|
<strong>Raised serum-IgE levels and defective neutrophil chemotaxis in three children with eczema and recurrent bacterial infections.</strong>
|
|
Lancet 303: 183-187, 1974. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 4129875]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(74)92493-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoger, P. H., Boltshauser, E., Hitzig, W. H.
|
|
<strong>Craniosynostosis in hyper-IgE-syndrome.</strong>
|
|
Europ. J. Pediat. 144: 414-417, 1985.
|
|
|
|
|
|
[PubMed: 4076261]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00441793]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N., Freeman, A. F., Demidowich, A., Davis, J., Turner, M. L., Anderson, V. L., Darnell, D. N., and 13 others.
|
|
<strong>STAT3 mutations in the hyper-IgE syndrome.</strong>
|
|
New Eng. J. Med. 357: 1608-1619, 2007.
|
|
|
|
|
|
[PubMed: 17881745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa073687]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jacobs, J. C., Norman, M. E.
|
|
<strong>A familial defect of neutrophil chemotaxis with asthma, eczema, and recurrent skin infections.</strong>
|
|
Pediat. Res. 11: 732-736, 1977.
|
|
|
|
|
|
[PubMed: 865918]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-197706000-00007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jung, L. K. L., Engelhard, D., Kapoor, N., Pih, K., Good, R. A.
|
|
<strong>Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.</strong>
|
|
Lancet 322: 185-187, 1983. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 6135027]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(83)90171-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kirchner, S. G., Sivit, C. J., Wright, P. F.
|
|
<strong>Hyperimmunoglobulinemia E syndrome: association with osteoporosis and recurrent fractures.</strong>
|
|
Radiology 156: 362 only, 1985.
|
|
|
|
|
|
[PubMed: 4011897]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1148/radiology.156.2.4011897]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leung, D. Y. M., Frankel, R., Wood, N., Geha, R. S.
|
|
<strong>Potentiation of human immunoglobulin E synthesis by plasma immunoglobulin E binding factors from patients with the hyperimmunoglobulin E syndrome.</strong>
|
|
J. Clin. Invest. 77: 952-957, 1986.
|
|
|
|
|
|
[PubMed: 3485112]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112395]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leung, D. Y. M., Geha, R. S.
|
|
<strong>Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome.</strong>
|
|
Hemat. Oncol. Clin. North Am. 2: 81-100, 1988.
|
|
|
|
|
|
[PubMed: 3279022]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lui, R. C., Inculet, R. I.
|
|
<strong>Job's syndrome: a rare cause of recurrent lung abscess in childhood.</strong>
|
|
Ann. Thorac. Surg. 50: 992-994, 1990.
|
|
|
|
|
|
[PubMed: 2241394]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0003-4975(90)91144-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lyons, J. J., Liu, Y., Ma, C. A., Yu, X., O'Connell, M. P., Lawrence, M. G., Zhang, Y., Karpe, K., Zhao, M., Siegel, A. M., Stone, K. D., Nelson, C., and 13 others.
|
|
<strong>ERBIN deficiency links STAT3 and TGF-beta pathway defects with atopy in humans.</strong>
|
|
J. Exp. Med. 214: 669-680, 2017. Note: Erratum: J. Exp. Med. 214: 1201 only, 2017.
|
|
|
|
|
|
[PubMed: 28126831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20161435]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ma, C. S., Chew, G. Y. J., Simpson, N., Priyadarshi, A., Wong, M., Grimbacher, B., Fulcher, D. A., Tangye, S. G., Cook, M. C.
|
|
<strong>Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3.</strong>
|
|
J. Exp. Med. 205: 1551-1557, 2008.
|
|
|
|
|
|
[PubMed: 18591410]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20080218]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mawhinney, H., Killen, M., Fleming, W. A., Roy, D. A.
|
|
<strong>The hyper-immunoglobulin E syndrome--a neutrophil chemotactic defect reversible by histamine H2 receptor blockade?</strong>
|
|
Clin. Immun. Immunopath. 17: 483-491, 1980.
|
|
|
|
|
|
[PubMed: 6108173]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0090-1229(80)90144-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., Davis, J., Hsu, A., Asher, A. I., O'Shea, J., Holland, S. M., Paul, W. E., Douek, D. C.
|
|
<strong>Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome.</strong>
|
|
Nature 452: 773-776, 2008.
|
|
|
|
|
|
[PubMed: 18337720]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06764]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Minegishi, Y., Saito, M., Tsuchiya, S., Tsuge, I., Takada, H., Hara, T., Kawamura, N., Ariga, T., Pasic, S., Stojkovic, O., Metin, A., Karasuyama, H.
|
|
<strong>Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.</strong>
|
|
Nature 448: 1058-1062, 2007.
|
|
|
|
|
|
[PubMed: 17676033]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06096]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Renner, E. D., Torgerson, T. R., Rylaarsdam, S., Anover-Sombke, S., Golob, K., LaFlam, T., Zhu, Q., Ochs, H. D.
|
|
<strong>STAT3 mutation in the original patient with Job's syndrome. (Letter)</strong>
|
|
New Eng. J. Med. 357: 1667-1668, 2007.
|
|
|
|
|
|
[PubMed: 17942886]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMc076367]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robinson, M. F., McGregor, R., Collins, R., Cheung, K.
|
|
<strong>Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease.</strong>
|
|
Am. J. Med. 73: 63-70, 1982.
|
|
|
|
|
|
[PubMed: 6979928]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(82)90927-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Siegel, A. M., Heimall, J., Freeman, A. F., Hsu, A. P., Brittain, E., Brenchley, J. M., Douek, D. C., Fahle, G. H., Cohen, J. I., Holland, S. M., Milner, J. D.
|
|
<strong>A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.</strong>
|
|
Immunity 35: 806-818, 2011.
|
|
|
|
|
|
[PubMed: 22118528]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.immuni.2011.09.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swim, A. T., Bradac, C., Craddock, P. R.
|
|
<strong>Levamisole in Job's syndrome. (Letter)</strong>
|
|
New Eng. J. Med. 307: 1528-1529, 1982.
|
|
|
|
|
|
[PubMed: 7144828]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198212093072424]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Urban, A., NCI Lymphoma Physicians Consortium, Pittaluga, S., Case Western Physicians Consortium, Freeman, A. F.
|
|
<strong>Malignancy in STAT3 deficient hyper IgE syndrome.</strong>
|
|
J. Clin. Immun. 42: 699-702, 2022. Note: Erratum: J. Clin. Immun. 42: 1348 only, 2022.
|
|
|
|
|
|
[PubMed: 35059947]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10875-021-01197-y]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Van Scoy, R. E., Hill, H. R., Ritts, R. E., Jr., Quie, P. G.
|
|
<strong>Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.</strong>
|
|
Ann. Intern. Med. 82: 766-771, 1975.
|
|
|
|
|
|
[PubMed: 1138587]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-82-6-766]
|
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|
|
|
|
</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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White, L. R., Iannetta, A., Kaplan, E. L., Davis, S. D., Wedgwood, R. J.
|
|
<strong>Leucocytes in Job's syndrome. (Letter)</strong>
|
|
Lancet 293: 630 only, 1969. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 4180157]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(69)91577-3]
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Witemeyer, S., Van Epps, D. E.
|
|
<strong>A familial defect in cellular chemotaxis associated with redheadedness and recurrent infection.</strong>
|
|
J. Pediat. 89: 33-37, 1976.
|
|
|
|
|
|
[PubMed: 932900]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(76)80922-5]
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