2981 lines
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Entry
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- #300635 - LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 2; XLP2
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- OMIM
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<p>
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<span class="h4">#300635</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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<li role="presentation">
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<a href="/clinicalSynopsis/300635"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS308240"> <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="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=LYMPHOPROLIFERATIVE SYNDROME, X-LINKED" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=275&Typ=Pat" title="X-linked lymphoproliferative disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">X-linked lymphoproliferati… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=27964&Typ=Pat" title="X-linked lymphoproliferative disease due to XIAP deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">X-linked lymphoproliferati… </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1406/" 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/9494" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300635[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2442" title="X-linked lymphoproliferative disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">X-linked lymphoproliferati…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=538934" title="X-linked lymphoproliferative disease due to XIAP deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">X-linked lymphoproliferati…</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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<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:0060706" 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/300635" 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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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1162830004<br />
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<strong>ORPHA:</strong> 2442, 538934<br />
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<strong>DO:</strong> 0060706<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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300635
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 2; XLP2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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XIAP DEFICIENCY
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/X/652?start=-3&limit=10&highlight=652">
|
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Xq25
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Lymphoproliferative syndrome, X-linked, 2
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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/300635"> 300635 </a>
|
|
</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="X-linked recessive">XLR</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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XIAP
|
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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/300079"> 300079 </a>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/300635" 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>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS308240" class="btn btn-info" role="button"> Phenotypic Series </a>
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|
<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>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/300635" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300635" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
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</div>
|
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- X-linked recessive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845977</a>, <a href="https://bioportal.bioontology.org/search?q=C1279481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1279481</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</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>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Recurrent respiratory infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806482&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806482</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002205" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002205</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002205" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002205</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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|
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|
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|
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|
|
</div>
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|
|
</div>
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|
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|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spleen </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Splenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Inflammatory bowel disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/24526004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">24526004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0021390&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021390</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002037" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002037</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002037" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002037</a>]</span><br /> -
|
|
Colitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64226004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64226004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K52.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K52.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009319&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009319</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002583" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002583</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002583" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002583</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">
|
|
|
|
- Erythema nodosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32861005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32861005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/695.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">695.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012219" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012219</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012219" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012219</a>]</span><br /> -
|
|
Skin infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/108365000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">108365000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037278&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037278</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100658" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100658</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100658" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100658</a>]</span><br /> -
|
|
Folliculitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/721130001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">721130001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13600006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13600006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016436&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016436</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025084</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025084</a>]</span><br /> -
|
|
Acne <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88616000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88616000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11381005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11381005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L70.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L70.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L70.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L70.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L70" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L70</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0718217&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0718217</a>, <a href="https://bioportal.bioontology.org/search?q=C0702166&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0702166</a>, <a href="https://bioportal.bioontology.org/search?q=C0001144&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001144</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001061" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001061</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001061" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001061</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
</div>
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|
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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> HEMATOLOGY </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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|
|
- Pancytopenia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127034005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127034005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/284.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">284.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span><br /> -
|
|
Aplastic anemia (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/306058006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">306058006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/304132006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">304132006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/284.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">284.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001915" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001915</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001915" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001915</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> IMMUNOLOGY </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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|
|
- Primary immunodeficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/58606001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">58606001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0398686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0398686</a>]</span><br /> -
|
|
Recurrent infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/451991000124106" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">451991000124106</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239998&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239998</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span><br /> -
|
|
Recurrent fever <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/A68.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">A68.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/A68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">A68</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/087.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">087.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/087" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">087</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035021&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035021</a>, <a href="https://bioportal.bioontology.org/search?q=C3714772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714772</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span><br /> -
|
|
Hemophagocytic lymphohistiocytosis (HLH) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538756</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/234437005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">234437005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D76.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D76.1</a>]</span><br /> -
|
|
EBV infection (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/240530001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">240530001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149678&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149678</a>]</span><br /> -
|
|
Increased susceptibility to EBV infection <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3554551&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3554551</a>]</span><br /> -
|
|
Decreased iNKT cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538758</a>]</span><br /> -
|
|
Increased serum IL18 <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538759&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538759</a>]</span><br /> -
|
|
Decreased TNF-alpha release from monocytes after stimulation due to defective NOD2 signaling <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538760&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538760</a>]</span><br /> -
|
|
Increased sensitivity of T cells to activation-induced cell death (AICD) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538761&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538761</a>]</span><br /> -
|
|
Decreased CD19+ switched B cells (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538762&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538762</a>]</span><br /> -
|
|
Hypogammaglobulinemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/119250001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">119250001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D80.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D80.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/279.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">279.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086438&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086438</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span><br />
|
|
|
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</span>
|
|
</div>
|
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</div>
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</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Highly variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839039&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839039</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
|
|
Onset in first decades of life, usually early childhood<br /> -
|
|
Later onset can occur<br /> -
|
|
Death can occur<br /> -
|
|
Males are more severely affected<br /> -
|
|
Some female carries may have milder manifestations<br /> -
|
|
The incidence of mutation in XIAP leading to XLP2 is estimated to be 1 to 2 cases per million live births<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the X-linked inhibitor of apoptosis gene (XIAP, <a href="/entry/300079#0001">300079.0001</a>)<br />
|
|
|
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</span>
|
|
</div>
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|
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</div>
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</div>
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<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
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|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Lymphoproliferative syndrome
|
|
- <a href="/phenotypicSeries/PS308240">PS308240</a>
|
|
- 5 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/710?start=-3&limit=10&highlight=710"> 5q33.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613011"> Lymphoproliferative syndrome 1 </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/613011"> 613011 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/186973"> ITK </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/186973"> 186973 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/51?start=-3&limit=10&highlight=51"> 12p13.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615122"> Lymphoproliferative syndrome 2 </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/615122"> 615122 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/186711"> CD27 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
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<p>A number sign (#) is used with this entry because of evidence that X-linked lymphoproliferative syndrome-2 (XLP2) is caused by mutation in the gene encoding the X-linked inhibitor of apoptosis (XIAP; <a href="/entry/300079">300079</a>) on chromosome Xq25.</p>
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<p>XLP2 is an X-linked primary immune deficiency with symptom onset usually in the first years of life, although later onset may occur. Features are compatible with immune dysregulation and include hemophagocytic lymphohistiocytosis (HLH), often associated with chronic Epstein-Barr virus (EBV) infection, splenomegaly, fever, colitis or inflammatory bowel disease (IBD), and recurrent infections. Laboratory abnormalities are variable, but can include hypogammaglobulinemia, cytopenias, and low levels of a particular subset of T cells known as NKT (or iNKT) cells. Functional studies show increased sensitivity of T cells to apoptosis (activation-induced cell death, AICD), impaired cytokine production, including of TNF-alpha (TNFA; <a href="/entry/191160">191160</a>), and general dysregulation of the immune pathway, such as increased levels of IL18 (<a href="/entry/600953">600953</a>). However, circulating levels of lymphocytes and NK cells are usually normal. Many patients die from fulminant HLH, and the only curative treatment is a hematopoietic stem cell transplant, although this procedure has been associated with a poor prognosis. Female mutation carriers are usually asymptomatic, although some female carriers may have less severe manifestations, which appears to depend on X-inactivation patterns (summary by <a href="#8" class="mim-tip-reference" title="Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T. <strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong> J. Clin. Immun. 32: 411-420, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228567</a>] [<a href="https://doi.org/10.1007/s10875-011-9638-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22228567">Yang et al., 2012</a>; review by <a href="#2" class="mim-tip-reference" title="Latour, S., Aguilar, C. <strong>XIAP deficiency syndrome in humans.</strong> Semin. Cell Dev. Biol. 39: 115-123, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25666262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25666262</a>] [<a href="https://doi.org/10.1016/j.semcdb.2015.01.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25666262">Latour and Aguilar, 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25666262+22228567" 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="Latour, S., Aguilar, C. <strong>XIAP deficiency syndrome in humans.</strong> Semin. Cell Dev. Biol. 39: 115-123, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25666262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25666262</a>] [<a href="https://doi.org/10.1016/j.semcdb.2015.01.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25666262">Latour and Aguilar (2015)</a> provided a detailed review of XIAP deficiency, including clinical features, molecular genetics, and pathophysiology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25666262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a general phenotypic description and a discussion of genetic heterogeneity of X-linked lymphoproliferative syndrome, see XLP1 (<a href="/entry/308240">308240</a>).</p>
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<p><a href="#5" class="mim-tip-reference" title="Rigaud, S., Fondaneche, M.-C., Lambert, N., Pasquier, B., Mateo, V., Soulas, P., Galicier, L., Le Deist, F., Rieux-Laucat, F., Revy, P., Fischer, A., de Saint Basile, G., Latour, S. <strong>XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.</strong> Nature 444: 110-114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080092</a>] [<a href="https://doi.org/10.1038/nature05257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17080092">Rigaud et al. (2006)</a> reported 12 male patients from 3 unrelated families with XLP2. Eight patients from 2 unrelated families were diagnosed in the first years of life. In the third family, 2 brothers were diagnosed at ages 20 years and 0.5 years, and they both died of HLH at diagnosis; their nephew was diagnosed at age 22 years. Eleven of 12 patients had hemophagocytic lymphohistiocytosis, which was associated with Epstein-Barr virus (EBV) infection in 8 patients. Four patients had hypogammaglobulinemia, 2 developed inflammatory bowel disease (IBD), and 9 patients had hepatosplenomegaly. There was no gross abnormality in lymphocyte cell population in these patients, although flow cytometry studies showed that the patients had low levels of NKT cells, and patient lymphocytes were more susceptible to apoptotic stimuli, which could be rescued by expression of XIAP. In all, 4 patients died at ages 6 months, 11 years, 20 years, and 41 years, respectively. Female carriers were unaffected. <a href="#5" class="mim-tip-reference" title="Rigaud, S., Fondaneche, M.-C., Lambert, N., Pasquier, B., Mateo, V., Soulas, P., Galicier, L., Le Deist, F., Rieux-Laucat, F., Revy, P., Fischer, A., de Saint Basile, G., Latour, S. <strong>XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.</strong> Nature 444: 110-114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080092</a>] [<a href="https://doi.org/10.1038/nature05257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17080092">Rigaud et al. (2006)</a> noted that the clinical phenotype of patients with XLP2 was similar to that observed in patients with XLP1, although patients with XLP2 often had splenomegaly, which was the first clinical manifestation of their condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17080092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., Serpe, J. M., Dasu, T., Tschannen, M. R., Veith, R. L., Basehore, M. J., Broeckel, U., and 10 others. <strong>Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease.</strong> Genet. Med. 13: 255-262, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21173700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21173700</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3182088158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21173700">Worthey et al. (2011)</a> reported a boy who presented at 15 months of age with perianal abscesses and proctitis, progressing to transmural pancolitis with colocutaneous fistula, consistent with a Crohn disease (see <a href="/entry/266600">266600</a>)-like illness. The age and severity suggested an underlying immune defect, but despite comprehensive clinical evaluation a definitive diagnosis was not obtained. Whole-exome sequencing identified a cys-to-tyr substitution at a highly conserved cysteine residue in the XIAP gene (<a href="/entry/300079#0004">300079.0004</a>). This protein was not previously associated with Crohn disease but has a central role in the proinflammatory response and bacterial sensing through the NOD (<a href="/entry/605980">605980</a>) signaling pathway. Based on this finding, an allogeneic hematopoietic progenitor cell transplant was performed to prevent the development of life-threatening hemophagocytic lymphohistiocytosis, in concordance with the recommended treatment for X-linked inhibitor of apoptosis deficiency. At more than 42 days posttransplant the child was able to eat and drink and there had been no recurrence of gastrointestinal disease, suggesting that the mutation also drove the gastrointestinal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21173700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T. <strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong> J. Clin. Immun. 32: 411-420, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228567</a>] [<a href="https://doi.org/10.1007/s10875-011-9638-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22228567">Yang et al. (2012)</a> reported 9 Japanese boys from 6 unrelated families with XLP2 confirmed by genetic analysis. Three of the patients had previously been reported (<a href="#4" class="mim-tip-reference" title="Pachlopnik Schmid, J., Canioni, D., Moshous, D., Touzot, F., Mahlaoui, N., Hauck, F., Kanegane, H., Lopez-Granados, E., Mejstrikova, E., Pellier, I., Galicier, L., Galambrun, C., and 21 others. <strong>Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency).</strong> Blood 117: 1522-1529, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21119115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21119115</a>] [<a href="https://doi.org/10.1182/blood-2010-07-298372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21119115">Pachlopnik Schmid et al., 2011</a>; <a href="#9" class="mim-tip-reference" title="Zhao, M., Kanegane, H., Ouchi, K., Imamura, T., Latour, S., Miyawaki, T. <strong>A novel XIAP mutation in a Japanese boy with recurrent pancytopenia and splenomegaly.</strong> Haematologica 95: 688-689, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20015872/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20015872</a>] [<a href="https://doi.org/10.3324/haematol.2009.018010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20015872">Zhao et al., 2010</a>). Eight of the patients presented between 2 months and 2 years of age with disease symptoms. Five had recurrent HLH, fever, splenomegaly, and cytopenia. EBV infection was found in 4 patients, all of whom had HLH, and hypogammaglobulinemia was found in 2 patients. Other common features included fever, cytopenia, and splenomegaly. Most patients with HLH were treated with corticosteroids with or without cyclosporin A to prevent a rapidly fatal disease course. Two patients presented with colitis; one of these was the maternal uncle of the family's proband, and died at age 4 before the diagnosis of XLP2. There was some variability: 1 patient (patient 4) was a 15-year-old boy with recurrent infections and hypogammaglobulinemia without additional symptoms, whereas another patient (patient 3.2) was asymptomatic at age 17 years, although his brother presented at age 2 months and had EBV-associated recurrent HLH and most features of the disorder. None of the patients developed lymphoma. The patients had decreased levels of a specific type of NKT cells within the CD3+ T cell compartment that express an invariantly rearranged T-cell receptor consisting of TCRV-alpha-24 and TCRV-beta-11 chains (iNKT cells). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21119115+22228567+20015872" 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 follow-up study of <a href="#8" class="mim-tip-reference" title="Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T. <strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong> J. Clin. Immun. 32: 411-420, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228567</a>] [<a href="https://doi.org/10.1007/s10875-011-9638-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22228567">Yang et al. (2012)</a>, <a href="#3" class="mim-tip-reference" title="Nishida, N., Yang, X., Takasaki, I., Imai, K., Kato, K., Inoue, Y., Imamura, T., Miyashita, R., Kato, F., Yamaide, A., Mori, M., Saito, S., Hara, J., Adachi, Y., Miyawaki, T., Kanegane, H. <strong>Dysgammaglobulinemia associated with glu349del, a hypomorphic XIAP mutation.</strong> J. Invest. Allergol. Clin. Immun. 25: 205-213, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26182687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26182687</a>]" pmid="26182687">Nishida et al. (2015)</a> identified 8 additional patients with XLP2 from 6 Japanese families. Six patients from 4 families had typical features of the disorder, including recurrent HLH (5 patients), splenomegaly (2 patients), and/or colitis (2 patients). The onset of symptoms was highly variable, ranging from 1 month to 12 years; at the time of the report, the ages of the patients ranged from 2 to 47 years. Including the previously reported patients, <a href="#3" class="mim-tip-reference" title="Nishida, N., Yang, X., Takasaki, I., Imai, K., Kato, K., Inoue, Y., Imamura, T., Miyashita, R., Kato, F., Yamaide, A., Mori, M., Saito, S., Hara, J., Adachi, Y., Miyawaki, T., Kanegane, H. <strong>Dysgammaglobulinemia associated with glu349del, a hypomorphic XIAP mutation.</strong> J. Invest. Allergol. Clin. Immun. 25: 205-213, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26182687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26182687</a>]" pmid="26182687">Nishida et al. (2015)</a> found that 3 had reduced numbers of CD19+ switched B cells. Patient cells showed increased AICD of T lymphocytes compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26182687+22228567" 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="Dziadzio, M., Ammann, S., Canning, C., Boyle, F., Hassan, A., Cale, C., Elawad, M., Fiil, B. K., Gyrd-Hansen, M., Salzer, U., Speckmann, C., Grimbacher, B. <strong>Symptomatic male and female carriers in a large Caucasian kindred with XIAP deficiency.</strong> J. Clin. Immun. 35: 439-444, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25943627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25943627</a>] [<a href="https://doi.org/10.1007/s10875-015-0166-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25943627">Dziadzio et al. (2015)</a> reported a large Caucasian family with XLP2, including 6 affected males. There was wide phenotypic variability. Four males had colitis with onset ranging from infancy to age 12, 5 had skin involvement, including boils and erythema nodosum (EN), and 3 had recurrent infections (V.20, V.22, and V.24), mainly respiratory. Only 2 patients (V.22 and V.25) had features consistent with HLH, and 3 were positive for EBV (V.20, V.22, and V.24). Three boys died at ages 2, 12, and 16 years (V.25, V.24, and V.19, respectively), including 1 who died after a bone marrow transplant. The least severely affected male (V.22) was a 30-year-old man who had 1 episode of an unusual febrile illness at age 15 and had recurrent respiratory infections, chronic acne, and folliculitis. Six of 7 female carriers were affected to varying degrees with erythema nodosum (EN) and/or variable bowel symptoms, including IBD and irritable bowel syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25943627" 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="Yang, X., Hoshino, A., Taga, T., Kunitsu, T., Ikeda, Y., Yasumi, T., Yoshida, K., Wada, T., Miyake, K., Kubota, T., Okuno, Y., Muramatsu, H., Adachi, Y., Miyano, S., Ogawa, S., Kojima, S., Kanegane, H. <strong>A female patient with incomplete hemophagocytic lymphohistiocytosis caused by a heterozygous XIAP mutation associated with non-random X-chromosome inactivation skewed towards the wild-type XIAP allele.</strong> J. Clin. Immun. 35: 244-248, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25744037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25744037</a>] [<a href="https://doi.org/10.1007/s10875-015-0144-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25744037">Yang et al. (2015)</a> reported a Japanese family in which 3 sibs, 2 boys and a girl, had manifestations of XLP2. The boys were more severely affected, but all 3 had pancytopenia, fever, and evidence of EBV infection. The boys had splenomegaly. The boys developed HLH in infancy and at age 5 years, respectively, whereas the girl presented at age 7 years with pancytopenia but did not completely fulfill the criteria for HLH, and was considered to have 'incomplete HLH.' None had hypogammaglobulinemia. Genetic studies showed that the boys were hemizygous for a truncating mutation in the XIAP gene, and the mother and daughter were heterozygous for the mutation. X-chromosome inactivation studies in the daughter showed a highly skewed pattern, with preferential expression of the mutant allele and nonrandom inactivation of the paternal wildtype allele in peripheral blood and hair root cells. The asymptomatic mother, who was heterozygous for the mutation, had a random pattern of X-inactivation. Cells from all 3 affected sibs showed decreased XIAP protein expression, impaired NOD2 (<a href="/entry/605956">605956</a>) signaling with decreased production of TNF-alpha (TNFA; <a href="/entry/191160">191160</a>), and augmented AICD of peripheral blood mononuclear cells (PBMC). The patients also had marked elevation of serum IL18 (<a href="/entry/600953">600953</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25744037" 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>Clinical Variability</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Nishida, N., Yang, X., Takasaki, I., Imai, K., Kato, K., Inoue, Y., Imamura, T., Miyashita, R., Kato, F., Yamaide, A., Mori, M., Saito, S., Hara, J., Adachi, Y., Miyawaki, T., Kanegane, H. <strong>Dysgammaglobulinemia associated with glu349del, a hypomorphic XIAP mutation.</strong> J. Invest. Allergol. Clin. Immun. 25: 205-213, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26182687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26182687</a>]" pmid="26182687">Nishida et al. (2015)</a> reported 3 unrelated Japanese boys with dysgammaglobulinemia associated with a specific mutation in the XIAP gene (glu349del; <a href="/entry/300079#0005">300079.0005</a>). One of the patients had previously been reported by <a href="#8" class="mim-tip-reference" title="Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T. <strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong> J. Clin. Immun. 32: 411-420, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228567</a>] [<a href="https://doi.org/10.1007/s10875-011-9638-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22228567">Yang et al. (2012)</a> (patient 4). These patients had recurrent infections and hypogammaglobulinemia without additional symptoms, specifically no HLH or colitis, although 1 developed aplastic anemia and required a hematopoietic stem cell transplant. Patient cells showed normal XIAP expression, but 2 patients had decreased numbers of CD19+ switched B cells. Patient cells did not showed increased AICD of T lymphocytes compared to controls. Microarray analysis indicated that the gene expression patterns were different in patients with the E349del mutation compared to patients with other mutations in the XIAP gene. Patients with E349del had 10-fold lower expression of a number of genes, including those involved in B cell development and Ig levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26182687+22228567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of XLP2 in the families reported by <a href="#5" class="mim-tip-reference" title="Rigaud, S., Fondaneche, M.-C., Lambert, N., Pasquier, B., Mateo, V., Soulas, P., Galicier, L., Le Deist, F., Rieux-Laucat, F., Revy, P., Fischer, A., de Saint Basile, G., Latour, S. <strong>XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.</strong> Nature 444: 110-114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080092</a>] [<a href="https://doi.org/10.1038/nature05257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17080092">Rigaud et al. (2006)</a> and <a href="#6" class="mim-tip-reference" title="Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., Serpe, J. M., Dasu, T., Tschannen, M. R., Veith, R. L., Basehore, M. J., Broeckel, U., and 10 others. <strong>Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease.</strong> Genet. Med. 13: 255-262, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21173700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21173700</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3182088158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21173700">Worthey et al. (2011)</a> was consistent with X-linked recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21173700+17080092" 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 transmission pattern of XLP2 in the family reported by <a href="#1" class="mim-tip-reference" title="Dziadzio, M., Ammann, S., Canning, C., Boyle, F., Hassan, A., Cale, C., Elawad, M., Fiil, B. K., Gyrd-Hansen, M., Salzer, U., Speckmann, C., Grimbacher, B. <strong>Symptomatic male and female carriers in a large Caucasian kindred with XIAP deficiency.</strong> J. Clin. Immun. 35: 439-444, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25943627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25943627</a>] [<a href="https://doi.org/10.1007/s10875-015-0166-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25943627">Dziadzio et al. (2015)</a> was consistent with X-linked dominant inheritance with a less severe phenotype in females compared to males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25943627" 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 affected members, all males, of 3 families with XLP2, <a href="#5" class="mim-tip-reference" title="Rigaud, S., Fondaneche, M.-C., Lambert, N., Pasquier, B., Mateo, V., Soulas, P., Galicier, L., Le Deist, F., Rieux-Laucat, F., Revy, P., Fischer, A., de Saint Basile, G., Latour, S. <strong>XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.</strong> Nature 444: 110-114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080092</a>] [<a href="https://doi.org/10.1038/nature05257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17080092">Rigaud et al. (2006)</a> identified hemizygous mutations of the XIAP gene. One family carried a deletion of the cytidine at nucleotide 291 (<a href="/entry/300079#0001">300079.0001</a>), one a premature termination mutation (<a href="/entry/300079#0002">300079.0002</a>), and the third a deletion encompassing exon 2 (<a href="/entry/300079#0003">300079.0003</a>). The mothers of affected individuals were asymptomatic heterozygous carriers. The mutations were found by linkage analysis followed by candidate gene sequencing. Patient lymphocytes showed absence of the XIAP protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17080092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., Serpe, J. M., Dasu, T., Tschannen, M. R., Veith, R. L., Basehore, M. J., Broeckel, U., and 10 others. <strong>Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease.</strong> Genet. Med. 13: 255-262, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21173700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21173700</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3182088158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21173700">Worthey et al. (2011)</a> identified a missense mutation of a highly conserved cysteine in the XIAP gene (C203Y; <a href="/entry/300079#0004">300079.0004</a>) in a boy with XLP2 manifest as intractable inflammatory bowel disease. His asymptomatic mother carried the mutation; she had evidence of skewed X-inactivation in NK, B, and T helper cells. Functional assays of patient peripheral mononuclear cells showed an increased susceptibility to AICD and defective responsiveness to NOD2 (<a href="/entry/605956">605956</a>) ligands, consistent with loss of normal XIAP function in apoptosis and NOD2 signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21173700" 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 9 Japanese male patients from 6 unrelated Japanese families with XLP2, <a href="#8" class="mim-tip-reference" title="Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T. <strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong> J. Clin. Immun. 32: 411-420, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228567</a>] [<a href="https://doi.org/10.1007/s10875-011-9638-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22228567">Yang et al. (2012)</a> identified 6 different truncating mutations in the XIAP gene (see, e.g., <a href="/entry/300079#0005">300079.0005</a>-<a href="/entry/300079#0007">300079.0007</a>). The mutations were found by direct screening of the XIAP gene after exclusion of mutations in the SH2D1A gene (<a href="/entry/300490">300490</a>). The mothers of patients from families 1 through 5 were heterozygous carriers of the mutations, whereas the mother of 2 sibs (family 6) did not carry the mutation in peripheral blood, suggesting germline mosaicism. Flow cytometric analysis of patient lymphocytes showed decreased XIAP expression in 7 of 8 patients; low-normal expression was found in a patient (patient 4) with an in-frame deletion mutation (E349del; <a href="/entry/300079#0005">300079.0005</a>) and a milder phenotype with only hypogammaglobulinemia and recurrent infections. The expression pattern of XIAP in carrier mother cells was variably reduced or showed a bimodal pattern. Western blot analysis, performed on 3 patients, showed decreased XIAP levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22228567" 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 6 affected males from a large Caucasian family with XLP2, <a href="#1" class="mim-tip-reference" title="Dziadzio, M., Ammann, S., Canning, C., Boyle, F., Hassan, A., Cale, C., Elawad, M., Fiil, B. K., Gyrd-Hansen, M., Salzer, U., Speckmann, C., Grimbacher, B. <strong>Symptomatic male and female carriers in a large Caucasian kindred with XIAP deficiency.</strong> J. Clin. Immun. 35: 439-444, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25943627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25943627</a>] [<a href="https://doi.org/10.1007/s10875-015-0166-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25943627">Dziadzio et al. (2015)</a> identified a truncating mutation in the XIAP gene (<a href="/entry/300079#0008">300079.0008</a>). There were 7 female carriers, 6 of whom were symptomatic to varying degrees. Flow cytometric analysis of peripheral cells from 1 of the affected males showed absence of the XIAP protein and a severely abrogated response of monocytes to NOD2, with decreased TNF-alpha (<a href="/entry/191160">191160</a>) production. Flow cytometric analysis of lymphocyte subsets and monocytes from 3 female carriers revealed preferential expression of XIAP wildtype protein and normal NOD2 function. However, the most severely affected female carrier (patient IV.9) with IBD and EN had random X-inactivation, resulting in expression of the mutated XIAP protein in her monocytes and impaired NOD2 responses in vitro. These findings indicated that the pattern of X-inactivation can influence the phenotype in female carriers. The findings also indicated that impaired NOD2 signaling is a driving pathophysiologic mechanism of the disorder. In addition, the truncated mutation also resulted in increased AICD of patient-derived T-cell blasts in vitro, suggesting that the mutation also affected the antiapoptotic properties of XIAP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25943627" 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 incidence of mutations in XIAP leading to XLP2 is estimated to be 1 to 2 cases per million live births (review by <a href="#2" class="mim-tip-reference" title="Latour, S., Aguilar, C. <strong>XIAP deficiency syndrome in humans.</strong> Semin. Cell Dev. Biol. 39: 115-123, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25666262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25666262</a>] [<a href="https://doi.org/10.1016/j.semcdb.2015.01.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25666262">Latour and Aguilar, 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25666262" 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 review, <a href="#2" class="mim-tip-reference" title="Latour, S., Aguilar, C. <strong>XIAP deficiency syndrome in humans.</strong> Semin. Cell Dev. Biol. 39: 115-123, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25666262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25666262</a>] [<a href="https://doi.org/10.1016/j.semcdb.2015.01.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25666262">Latour and Aguilar (2015)</a> noted that studies have shown that certain strains of Xiap-deficient mice have compromised immunity leading to decreased survival when infected with certain pathogens, including intracellular bacteria and viruses. These infections are associated with splenomegaly and compromised innate immunity with altered cytokine production. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25666262" 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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<strong>REFERENCES</strong>
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<a id="Dziadzio2015" class="mim-anchor"></a>
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Dziadzio, M., Ammann, S., Canning, C., Boyle, F., Hassan, A., Cale, C., Elawad, M., Fiil, B. K., Gyrd-Hansen, M., Salzer, U., Speckmann, C., Grimbacher, B.
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<strong>Symptomatic male and female carriers in a large Caucasian kindred with XIAP deficiency.</strong>
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J. Clin. Immun. 35: 439-444, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25943627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25943627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25943627" 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/s10875-015-0166-0" target="_blank">Full Text</a>]
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<a id="Latour2015" class="mim-anchor"></a>
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Latour, S., Aguilar, C.
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<strong>XIAP deficiency syndrome in humans.</strong>
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Semin. Cell Dev. Biol. 39: 115-123, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25666262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25666262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25666262" 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.semcdb.2015.01.015" target="_blank">Full Text</a>]
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<a id="Nishida2015" class="mim-anchor"></a>
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Nishida, N., Yang, X., Takasaki, I., Imai, K., Kato, K., Inoue, Y., Imamura, T., Miyashita, R., Kato, F., Yamaide, A., Mori, M., Saito, S., Hara, J., Adachi, Y., Miyawaki, T., Kanegane, H.
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<strong>Dysgammaglobulinemia associated with glu349del, a hypomorphic XIAP mutation.</strong>
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J. Invest. Allergol. Clin. Immun. 25: 205-213, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26182687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26182687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26182687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Pachlopnik Schmid, J., Canioni, D., Moshous, D., Touzot, F., Mahlaoui, N., Hauck, F., Kanegane, H., Lopez-Granados, E., Mejstrikova, E., Pellier, I., Galicier, L., Galambrun, C., and 21 others.
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<strong>Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency).</strong>
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Blood 117: 1522-1529, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21119115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21119115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21119115" 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-2010-07-298372" target="_blank">Full Text</a>]
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<a id="Rigaud2006" class="mim-anchor"></a>
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Rigaud, S., Fondaneche, M.-C., Lambert, N., Pasquier, B., Mateo, V., Soulas, P., Galicier, L., Le Deist, F., Rieux-Laucat, F., Revy, P., Fischer, A., de Saint Basile, G., Latour, S.
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<strong>XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.</strong>
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Nature 444: 110-114, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17080092" 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/nature05257" target="_blank">Full Text</a>]
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<a id="Worthey2011" class="mim-anchor"></a>
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Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., Serpe, J. M., Dasu, T., Tschannen, M. R., Veith, R. L., Basehore, M. J., Broeckel, U., and 10 others.
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<strong>Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease.</strong>
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Genet. Med. 13: 255-262, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21173700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21173700</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21173700" 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/10.1097/GIM.0b013e3182088158" target="_blank">Full Text</a>]
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<a id="Yang2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, X., Hoshino, A., Taga, T., Kunitsu, T., Ikeda, Y., Yasumi, T., Yoshida, K., Wada, T., Miyake, K., Kubota, T., Okuno, Y., Muramatsu, H., Adachi, Y., Miyano, S., Ogawa, S., Kojima, S., Kanegane, H.
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<strong>A female patient with incomplete hemophagocytic lymphohistiocytosis caused by a heterozygous XIAP mutation associated with non-random X-chromosome inactivation skewed towards the wild-type XIAP allele.</strong>
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J. Clin. Immun. 35: 244-248, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25744037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25744037</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25744037" 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/s10875-015-0144-6" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Yang2012" class="mim-anchor"></a>
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Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T.
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<strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong>
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J. Clin. Immun. 32: 411-420, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22228567" 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/s10875-011-9638-z" target="_blank">Full Text</a>]
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Zhao, M., Kanegane, H., Ouchi, K., Imamura, T., Latour, S., Miyawaki, T.
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<strong>A novel XIAP mutation in a Japanese boy with recurrent pancytopenia and splenomegaly.</strong>
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Haematologica 95: 688-689, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20015872/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20015872</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20015872" 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/10.3324/haematol.2009.018010" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 11/28/2017
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Ada Hamosh - updated : 9/28/2012
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Ada Hamosh : 1/16/2007
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carol : 12/06/2017
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alopez : 12/05/2017<br>ckniffin : 11/28/2017<br>alopez : 10/02/2012<br>terry : 9/28/2012<br>wwang : 7/27/2011<br>alopez : 1/16/2007
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<strong>#</strong> 300635
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LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 2; XLP2
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<em>Alternative titles; symbols</em>
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XIAP DEFICIENCY
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<strong>SNOMEDCT:</strong> 1162830004;
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<strong>ORPHA:</strong> 2442, 538934;
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<strong>DO:</strong> 0060706;
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<strong>Phenotype-Gene Relationships</strong>
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<thead>
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</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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Xq25
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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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Lymphoproliferative syndrome, X-linked, 2
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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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300635
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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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X-linked recessive
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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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3
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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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XIAP
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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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300079
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<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>TEXT</strong>
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</span>
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</h4>
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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 X-linked lymphoproliferative syndrome-2 (XLP2) is caused by mutation in the gene encoding the X-linked inhibitor of apoptosis (XIAP; 300079) on chromosome Xq25.</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>Description</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>XLP2 is an X-linked primary immune deficiency with symptom onset usually in the first years of life, although later onset may occur. Features are compatible with immune dysregulation and include hemophagocytic lymphohistiocytosis (HLH), often associated with chronic Epstein-Barr virus (EBV) infection, splenomegaly, fever, colitis or inflammatory bowel disease (IBD), and recurrent infections. Laboratory abnormalities are variable, but can include hypogammaglobulinemia, cytopenias, and low levels of a particular subset of T cells known as NKT (or iNKT) cells. Functional studies show increased sensitivity of T cells to apoptosis (activation-induced cell death, AICD), impaired cytokine production, including of TNF-alpha (TNFA; 191160), and general dysregulation of the immune pathway, such as increased levels of IL18 (600953). However, circulating levels of lymphocytes and NK cells are usually normal. Many patients die from fulminant HLH, and the only curative treatment is a hematopoietic stem cell transplant, although this procedure has been associated with a poor prognosis. Female mutation carriers are usually asymptomatic, although some female carriers may have less severe manifestations, which appears to depend on X-inactivation patterns (summary by Yang et al., 2012; review by Latour and Aguilar, 2015). </p><p>Latour and Aguilar (2015) provided a detailed review of XIAP deficiency, including clinical features, molecular genetics, and pathophysiology. </p><p>For a general phenotypic description and a discussion of genetic heterogeneity of X-linked lymphoproliferative syndrome, see XLP1 (308240).</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 Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Rigaud et al. (2006) reported 12 male patients from 3 unrelated families with XLP2. Eight patients from 2 unrelated families were diagnosed in the first years of life. In the third family, 2 brothers were diagnosed at ages 20 years and 0.5 years, and they both died of HLH at diagnosis; their nephew was diagnosed at age 22 years. Eleven of 12 patients had hemophagocytic lymphohistiocytosis, which was associated with Epstein-Barr virus (EBV) infection in 8 patients. Four patients had hypogammaglobulinemia, 2 developed inflammatory bowel disease (IBD), and 9 patients had hepatosplenomegaly. There was no gross abnormality in lymphocyte cell population in these patients, although flow cytometry studies showed that the patients had low levels of NKT cells, and patient lymphocytes were more susceptible to apoptotic stimuli, which could be rescued by expression of XIAP. In all, 4 patients died at ages 6 months, 11 years, 20 years, and 41 years, respectively. Female carriers were unaffected. Rigaud et al. (2006) noted that the clinical phenotype of patients with XLP2 was similar to that observed in patients with XLP1, although patients with XLP2 often had splenomegaly, which was the first clinical manifestation of their condition. </p><p>Worthey et al. (2011) reported a boy who presented at 15 months of age with perianal abscesses and proctitis, progressing to transmural pancolitis with colocutaneous fistula, consistent with a Crohn disease (see 266600)-like illness. The age and severity suggested an underlying immune defect, but despite comprehensive clinical evaluation a definitive diagnosis was not obtained. Whole-exome sequencing identified a cys-to-tyr substitution at a highly conserved cysteine residue in the XIAP gene (300079.0004). This protein was not previously associated with Crohn disease but has a central role in the proinflammatory response and bacterial sensing through the NOD (605980) signaling pathway. Based on this finding, an allogeneic hematopoietic progenitor cell transplant was performed to prevent the development of life-threatening hemophagocytic lymphohistiocytosis, in concordance with the recommended treatment for X-linked inhibitor of apoptosis deficiency. At more than 42 days posttransplant the child was able to eat and drink and there had been no recurrence of gastrointestinal disease, suggesting that the mutation also drove the gastrointestinal disease. </p><p>Yang et al. (2012) reported 9 Japanese boys from 6 unrelated families with XLP2 confirmed by genetic analysis. Three of the patients had previously been reported (Pachlopnik Schmid et al., 2011; Zhao et al., 2010). Eight of the patients presented between 2 months and 2 years of age with disease symptoms. Five had recurrent HLH, fever, splenomegaly, and cytopenia. EBV infection was found in 4 patients, all of whom had HLH, and hypogammaglobulinemia was found in 2 patients. Other common features included fever, cytopenia, and splenomegaly. Most patients with HLH were treated with corticosteroids with or without cyclosporin A to prevent a rapidly fatal disease course. Two patients presented with colitis; one of these was the maternal uncle of the family's proband, and died at age 4 before the diagnosis of XLP2. There was some variability: 1 patient (patient 4) was a 15-year-old boy with recurrent infections and hypogammaglobulinemia without additional symptoms, whereas another patient (patient 3.2) was asymptomatic at age 17 years, although his brother presented at age 2 months and had EBV-associated recurrent HLH and most features of the disorder. None of the patients developed lymphoma. The patients had decreased levels of a specific type of NKT cells within the CD3+ T cell compartment that express an invariantly rearranged T-cell receptor consisting of TCRV-alpha-24 and TCRV-beta-11 chains (iNKT cells). </p><p>In a follow-up study of Yang et al. (2012), Nishida et al. (2015) identified 8 additional patients with XLP2 from 6 Japanese families. Six patients from 4 families had typical features of the disorder, including recurrent HLH (5 patients), splenomegaly (2 patients), and/or colitis (2 patients). The onset of symptoms was highly variable, ranging from 1 month to 12 years; at the time of the report, the ages of the patients ranged from 2 to 47 years. Including the previously reported patients, Nishida et al. (2015) found that 3 had reduced numbers of CD19+ switched B cells. Patient cells showed increased AICD of T lymphocytes compared to controls. </p><p>Dziadzio et al. (2015) reported a large Caucasian family with XLP2, including 6 affected males. There was wide phenotypic variability. Four males had colitis with onset ranging from infancy to age 12, 5 had skin involvement, including boils and erythema nodosum (EN), and 3 had recurrent infections (V.20, V.22, and V.24), mainly respiratory. Only 2 patients (V.22 and V.25) had features consistent with HLH, and 3 were positive for EBV (V.20, V.22, and V.24). Three boys died at ages 2, 12, and 16 years (V.25, V.24, and V.19, respectively), including 1 who died after a bone marrow transplant. The least severely affected male (V.22) was a 30-year-old man who had 1 episode of an unusual febrile illness at age 15 and had recurrent respiratory infections, chronic acne, and folliculitis. Six of 7 female carriers were affected to varying degrees with erythema nodosum (EN) and/or variable bowel symptoms, including IBD and irritable bowel syndrome. </p><p>Yang et al. (2015) reported a Japanese family in which 3 sibs, 2 boys and a girl, had manifestations of XLP2. The boys were more severely affected, but all 3 had pancytopenia, fever, and evidence of EBV infection. The boys had splenomegaly. The boys developed HLH in infancy and at age 5 years, respectively, whereas the girl presented at age 7 years with pancytopenia but did not completely fulfill the criteria for HLH, and was considered to have 'incomplete HLH.' None had hypogammaglobulinemia. Genetic studies showed that the boys were hemizygous for a truncating mutation in the XIAP gene, and the mother and daughter were heterozygous for the mutation. X-chromosome inactivation studies in the daughter showed a highly skewed pattern, with preferential expression of the mutant allele and nonrandom inactivation of the paternal wildtype allele in peripheral blood and hair root cells. The asymptomatic mother, who was heterozygous for the mutation, had a random pattern of X-inactivation. Cells from all 3 affected sibs showed decreased XIAP protein expression, impaired NOD2 (605956) signaling with decreased production of TNF-alpha (TNFA; 191160), and augmented AICD of peripheral blood mononuclear cells (PBMC). The patients also had marked elevation of serum IL18 (600953). </p><p><strong><em>Clinical Variability</em></strong></p><p>
|
|
Nishida et al. (2015) reported 3 unrelated Japanese boys with dysgammaglobulinemia associated with a specific mutation in the XIAP gene (glu349del; 300079.0005). One of the patients had previously been reported by Yang et al. (2012) (patient 4). These patients had recurrent infections and hypogammaglobulinemia without additional symptoms, specifically no HLH or colitis, although 1 developed aplastic anemia and required a hematopoietic stem cell transplant. Patient cells showed normal XIAP expression, but 2 patients had decreased numbers of CD19+ switched B cells. Patient cells did not showed increased AICD of T lymphocytes compared to controls. Microarray analysis indicated that the gene expression patterns were different in patients with the E349del mutation compared to patients with other mutations in the XIAP gene. Patients with E349del had 10-fold lower expression of a number of genes, including those involved in B cell development and Ig levels. </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>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
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</span>
|
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</h4>
|
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</div>
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|
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|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of XLP2 in the families reported by Rigaud et al. (2006) and Worthey et al. (2011) was consistent with X-linked recessive inheritance. </p><p>The transmission pattern of XLP2 in the family reported by Dziadzio et al. (2015) was consistent with X-linked dominant inheritance with a less severe phenotype in females compared to males. </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">
|
|
<p>In affected members, all males, of 3 families with XLP2, Rigaud et al. (2006) identified hemizygous mutations of the XIAP gene. One family carried a deletion of the cytidine at nucleotide 291 (300079.0001), one a premature termination mutation (300079.0002), and the third a deletion encompassing exon 2 (300079.0003). The mothers of affected individuals were asymptomatic heterozygous carriers. The mutations were found by linkage analysis followed by candidate gene sequencing. Patient lymphocytes showed absence of the XIAP protein. </p><p>Worthey et al. (2011) identified a missense mutation of a highly conserved cysteine in the XIAP gene (C203Y; 300079.0004) in a boy with XLP2 manifest as intractable inflammatory bowel disease. His asymptomatic mother carried the mutation; she had evidence of skewed X-inactivation in NK, B, and T helper cells. Functional assays of patient peripheral mononuclear cells showed an increased susceptibility to AICD and defective responsiveness to NOD2 (605956) ligands, consistent with loss of normal XIAP function in apoptosis and NOD2 signaling. </p><p>In 9 Japanese male patients from 6 unrelated Japanese families with XLP2, Yang et al. (2012) identified 6 different truncating mutations in the XIAP gene (see, e.g., 300079.0005-300079.0007). The mutations were found by direct screening of the XIAP gene after exclusion of mutations in the SH2D1A gene (300490). The mothers of patients from families 1 through 5 were heterozygous carriers of the mutations, whereas the mother of 2 sibs (family 6) did not carry the mutation in peripheral blood, suggesting germline mosaicism. Flow cytometric analysis of patient lymphocytes showed decreased XIAP expression in 7 of 8 patients; low-normal expression was found in a patient (patient 4) with an in-frame deletion mutation (E349del; 300079.0005) and a milder phenotype with only hypogammaglobulinemia and recurrent infections. The expression pattern of XIAP in carrier mother cells was variably reduced or showed a bimodal pattern. Western blot analysis, performed on 3 patients, showed decreased XIAP levels. </p><p>In 6 affected males from a large Caucasian family with XLP2, Dziadzio et al. (2015) identified a truncating mutation in the XIAP gene (300079.0008). There were 7 female carriers, 6 of whom were symptomatic to varying degrees. Flow cytometric analysis of peripheral cells from 1 of the affected males showed absence of the XIAP protein and a severely abrogated response of monocytes to NOD2, with decreased TNF-alpha (191160) production. Flow cytometric analysis of lymphocyte subsets and monocytes from 3 female carriers revealed preferential expression of XIAP wildtype protein and normal NOD2 function. However, the most severely affected female carrier (patient IV.9) with IBD and EN had random X-inactivation, resulting in expression of the mutated XIAP protein in her monocytes and impaired NOD2 responses in vitro. These findings indicated that the pattern of X-inactivation can influence the phenotype in female carriers. The findings also indicated that impaired NOD2 signaling is a driving pathophysiologic mechanism of the disorder. In addition, the truncated mutation also resulted in increased AICD of patient-derived T-cell blasts in vitro, suggesting that the mutation also affected the antiapoptotic properties of XIAP. </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>Population 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">
|
|
<p>The incidence of mutations in XIAP leading to XLP2 is estimated to be 1 to 2 cases per million live births (review by Latour and Aguilar, 2015). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>In a review, Latour and Aguilar (2015) noted that studies have shown that certain strains of Xiap-deficient mice have compromised immunity leading to decreased survival when infected with certain pathogens, including intracellular bacteria and viruses. These infections are associated with splenomegaly and compromised innate immunity with altered cytokine production. </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>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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Dziadzio, M., Ammann, S., Canning, C., Boyle, F., Hassan, A., Cale, C., Elawad, M., Fiil, B. K., Gyrd-Hansen, M., Salzer, U., Speckmann, C., Grimbacher, B.
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<strong>Symptomatic male and female carriers in a large Caucasian kindred with XIAP deficiency.</strong>
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J. Clin. Immun. 35: 439-444, 2015.
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[PubMed: 25943627]
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[Full Text: https://doi.org/10.1007/s10875-015-0166-0]
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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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Latour, S., Aguilar, C.
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<strong>XIAP deficiency syndrome in humans.</strong>
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Semin. Cell Dev. Biol. 39: 115-123, 2015.
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[PubMed: 25666262]
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[Full Text: https://doi.org/10.1016/j.semcdb.2015.01.015]
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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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Nishida, N., Yang, X., Takasaki, I., Imai, K., Kato, K., Inoue, Y., Imamura, T., Miyashita, R., Kato, F., Yamaide, A., Mori, M., Saito, S., Hara, J., Adachi, Y., Miyawaki, T., Kanegane, H.
|
|
<strong>Dysgammaglobulinemia associated with glu349del, a hypomorphic XIAP mutation.</strong>
|
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J. Invest. Allergol. Clin. Immun. 25: 205-213, 2015.
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[PubMed: 26182687]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Pachlopnik Schmid, J., Canioni, D., Moshous, D., Touzot, F., Mahlaoui, N., Hauck, F., Kanegane, H., Lopez-Granados, E., Mejstrikova, E., Pellier, I., Galicier, L., Galambrun, C., and 21 others.
|
|
<strong>Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency).</strong>
|
|
Blood 117: 1522-1529, 2011.
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[PubMed: 21119115]
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[Full Text: https://doi.org/10.1182/blood-2010-07-298372]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Rigaud, S., Fondaneche, M.-C., Lambert, N., Pasquier, B., Mateo, V., Soulas, P., Galicier, L., Le Deist, F., Rieux-Laucat, F., Revy, P., Fischer, A., de Saint Basile, G., Latour, S.
|
|
<strong>XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.</strong>
|
|
Nature 444: 110-114, 2006.
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[PubMed: 17080092]
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[Full Text: https://doi.org/10.1038/nature05257]
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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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Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., Serpe, J. M., Dasu, T., Tschannen, M. R., Veith, R. L., Basehore, M. J., Broeckel, U., and 10 others.
|
|
<strong>Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease.</strong>
|
|
Genet. Med. 13: 255-262, 2011.
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[PubMed: 21173700]
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[Full Text: https://doi.org/10.1097/GIM.0b013e3182088158]
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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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Yang, X., Hoshino, A., Taga, T., Kunitsu, T., Ikeda, Y., Yasumi, T., Yoshida, K., Wada, T., Miyake, K., Kubota, T., Okuno, Y., Muramatsu, H., Adachi, Y., Miyano, S., Ogawa, S., Kojima, S., Kanegane, H.
|
|
<strong>A female patient with incomplete hemophagocytic lymphohistiocytosis caused by a heterozygous XIAP mutation associated with non-random X-chromosome inactivation skewed towards the wild-type XIAP allele.</strong>
|
|
J. Clin. Immun. 35: 244-248, 2015.
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[PubMed: 25744037]
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[Full Text: https://doi.org/10.1007/s10875-015-0144-6]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Yang, X., Kanegane, H., Nishida, N., Imamura, T., Hamamoto, K., Miyashita, R., Imai, K., Nonoyama, S., Sanayama, K., Yamaide, A., Kato, F., Nagai, K., Ishii, E., van Zelm, M. C., Latour, S., Zhao, X.-D., Miyawaki, T.
|
|
<strong>Clinical and genetic characteristics of XIAP deficiency in Japan.</strong>
|
|
J. Clin. Immun. 32: 411-420, 2012.
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[PubMed: 22228567]
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[Full Text: https://doi.org/10.1007/s10875-011-9638-z]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Zhao, M., Kanegane, H., Ouchi, K., Imamura, T., Latour, S., Miyawaki, T.
|
|
<strong>A novel XIAP mutation in a Japanese boy with recurrent pancytopenia and splenomegaly.</strong>
|
|
Haematologica 95: 688-689, 2010.
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[PubMed: 20015872]
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[Full Text: https://doi.org/10.3324/haematol.2009.018010]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Cassandra L. Kniffin - updated : 11/28/2017<br>Ada Hamosh - updated : 9/28/2012
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Ada Hamosh : 1/16/2007
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carol : 12/06/2017<br>alopez : 12/05/2017<br>ckniffin : 11/28/2017<br>alopez : 10/02/2012<br>terry : 9/28/2012<br>wwang : 7/27/2011<br>alopez : 1/16/2007
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