2653 lines
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Entry
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- #610755 - MULTIPLE ENDOCRINE NEOPLASIA, TYPE IV; MEN4
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- OMIM
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<p>
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<span class="h4">#610755</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/610755"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS131100"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular 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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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<div><a href="https://clinicaltrials.gov/search?cond=MULTIPLE ENDOCRINE NEOPLASIA, TYPE IV" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20350&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK594826/" 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/8918" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=610755[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276152" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<span class="small">
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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:0080137" 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/610755" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0080137" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715907003<br />
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<strong>ORPHA:</strong> 276152<br />
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<strong>DO:</strong> 0080137<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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610755
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</span>
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</span>
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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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MULTIPLE ENDOCRINE NEOPLASIA, TYPE IV; MEN4
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</h3>
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</div>
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<div>
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<br />
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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/12/181?start=-3&limit=10&highlight=181">
|
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12p13.1
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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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Multiple endocrine neoplasia, type IV
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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/610755"> 610755 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<td>
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<span class="mim-font">
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CDKN1B
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/600778"> 600778 </a>
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</span>
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</td>
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</table>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/610755" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS131100" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
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<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
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|
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/610755" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/610755" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<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>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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<div>
|
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<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
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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> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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|
|
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Airways </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Bronchial carcinoid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013426&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013426</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
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|
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|
|
</div>
|
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|
|
</div>
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|
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|
|
|
|
|
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|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Kidneys </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Renal angiomyolipoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254921004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254921004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241961&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241961</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006772</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006772</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Acromegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74107003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74107003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001206&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001206</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033794" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033794</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033794" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033794</a>]</span><br /> -
|
|
Pituitary adenoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254956000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254956000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0032000&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0032000</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002893" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002893</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002893" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002893</a>]</span><br /> -
|
|
Parathyroid adenoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128474007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128474007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0262587&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0262587</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002897" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002897</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002897" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002897</a>]</span><br /> -
|
|
Carcinoid tumors <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D3A.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D3A.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007095&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007095</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100570" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100570</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100570" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100570</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Pancreatic endocrine neoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315004&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315004</a>]</span><br /> -
|
|
Papillary thyroid cancer <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1336196002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1336196002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255029007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255029007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238463&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238463</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002895" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002895</a>]</span><br /> -
|
|
Neuroendocrine cervical carcinoma <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013425</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset of tumors usually in adulthood<br /> -
|
|
Variable manifestations<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<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 cyclin-dependent kinase inhibitor-1B gene (CDKN1B, <a href="/entry/600778#0001">600778.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Multiple endocrine neoplasia
|
|
- <a href="/phenotypicSeries/PS131100">PS131100</a>
|
|
- 4 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/10/158?start=-3&limit=10&highlight=158"> 10q11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/171400"> Multiple endocrine neoplasia IIA </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/171400"> 171400 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/164761"> RET </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/164761"> 164761 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/158?start=-3&limit=10&highlight=158"> 10q11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162300"> Multiple endocrine neoplasia IIB </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<p>A number sign (#) is used with this entry because of evidence that multiple endocrine neoplasia type IV (MEN4) is caused by heterozygous mutation in the CDKN1B gene (<a href="/entry/600778">600778</a>) on chromosome 12p13.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of multiple endocrine neoplasia, see MEN1 (<a href="/entry/131100">131100</a>).</p>
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<p><a href="#6" class="mim-tip-reference" title="Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., Hofler, H., Fend, F., Graw, J., Atkinson, M. J. <strong>Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans.</strong> Proc. Nat. Acad. Sci. 103: 15558-15563, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 19213 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17030811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17030811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17030811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0603877103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17030811">Pellegata et al. (2006)</a> reported a 3-generation family with what appeared to be MEN1-related tumors. The proband was a 48-year-old Caucasian female who developed acromegaly and had a 3-cm pituitary tumor removed at age 30. Histology revealed an invasive pituitary adenoma with growth hormone hyperproduction, high mitotic activity, and cell atypia. At age 46, she was diagnosed with primary hyperparathyroidism; at the time of study, she had not yet undergone surgery. Her deceased father had acromegaly, and a brother died at age 39 from hypertension. Her older sister was diagnosed at 55 years of age with renal angiomyolipoma and that sister's son developed testicular cancer at 28 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17030811" 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="Georgitsi, M., Raitila, A., Karhu, A., van der Luijt, R. B., Aalfs, C. M., Sane, T., Vierimaa, O., Makinen, M. J., Tuppurainen, K., Paschke, R., Gimm, O., Koch, C. A., and 11 others. <strong>Germline CDKN1B/p27(Kip1) mutation in multiple endocrine neoplasia.</strong> J. Clin. Endocr. Metab. 92: 3321-3325, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17519308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17519308</a>] [<a href="https://doi.org/10.1210/jc.2006-2843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17519308">Georgitsi et al. (2007)</a> reported a Dutch woman with MEN4 who developed small-cell neuroendocrine cervical carcinoma, an ACTH-secreting pituitary adenoma, and hyperparathyroidism in her forties. She was also diagnosed with multiple sclerosis. She had no family history of endocrine tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17519308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Molatore, S., Marinoni, I., Lee, M., Pulz, E., Ambrosio, M. R., degli Uberti, E. C., Zatelli, M. C., Pellegata, N. S. <strong>A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.</strong> Hum. Mutat. 31: E1825-E1835, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20824794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20824794</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20824794[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20824794">Molatore et al. (2010)</a> reported a 79-year-old Caucasian woman with bronchial carcinoid tumor, a nonfunctioning pituitary microadenoma, parathyroid adenoma, and papillary thyroid carcinoma. She also had type 2 diabetes mellitus. She had no family history of endocrine tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20824794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Malanga, D., De Gisi, S., Riccardi, M., Scrima, M., De Marco, C., Robledo, M., Viglietto, G. <strong>Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with multiple endocrine neoplasia-like phenotype.</strong> Europ. J. Endocr. 166: 551-560, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22129891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22129891</a>] [<a href="https://doi.org/10.1530/EJE-11-0929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22129891">Malanga et al. (2012)</a> reported a 69-year-old Spanish woman with MEN4 manifest as gastric carcinoid tumor and hyperparathyroidism; there was no family history of endocrine neoplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22129891" 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="Tonelli, F., Giudici, F., Giusti, F., Marini, F., Cianferotti, L., Nesi, G., Brandi, M. L. <strong>A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.</strong> Europ. J. Endocr. 171: K7-K17, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24819502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24819502</a>] [<a href="https://doi.org/10.1530/EJE-14-0080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24819502">Tonelli et al. (2014)</a> reported a 53-year-old Italian woman with persistent hyperparathyroidism due to parathyroid adenomas and gastrointestinal neuroendocrine tumors; she also had a history of hypothyroidism due to Hashimoto thyroiditis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24819502" 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 MEN4 in the family reported by <a href="#6" class="mim-tip-reference" title="Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., Hofler, H., Fend, F., Graw, J., Atkinson, M. J. <strong>Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans.</strong> Proc. Nat. Acad. Sci. 103: 15558-15563, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 19213 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17030811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17030811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17030811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0603877103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17030811">Pellegata et al. (2006)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17030811" 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 48-year-old Caucasian female with primary hyperparathyroidism and a history of pituitary adenoma (MEN4), <a href="#6" class="mim-tip-reference" title="Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., Hofler, H., Fend, F., Graw, J., Atkinson, M. J. <strong>Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans.</strong> Proc. Nat. Acad. Sci. 103: 15558-15563, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 19213 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17030811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17030811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17030811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0603877103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17030811">Pellegata et al. (2006)</a> identified a nonsense mutation in the CDKN1B gene (<a href="/entry/600778#0001">600778.0001</a>). The mutation was also identified in her older sister who had renal angiomyolipoma, and in her youngest sister and that sister's teenaged daughter, who reported no symptoms but did not undergo thorough examination. Samples from a nephew with testicular cancer at age 28 and from her deceased father, who had acromegaly, were not available for analysis. The mutation was not found in 380 unrelated healthy controls. No mutations in the MEN1 gene (<a href="/entry/613733">613733</a>) were found in the proband or her older sister. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17030811" 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 Dutch woman with MEN4, <a href="#2" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., van der Luijt, R. B., Aalfs, C. M., Sane, T., Vierimaa, O., Makinen, M. J., Tuppurainen, K., Paschke, R., Gimm, O., Koch, C. A., and 11 others. <strong>Germline CDKN1B/p27(Kip1) mutation in multiple endocrine neoplasia.</strong> J. Clin. Endocr. Metab. 92: 3321-3325, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17519308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17519308</a>] [<a href="https://doi.org/10.1210/jc.2006-2843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17519308">Georgitsi et al. (2007)</a> identified a heterozygous truncating mutation in the CDKN1B gene (<a href="/entry/600778#0002">600778.0002</a>). Tumor tissue from the patient's cervical carcinoma showed loss of heterozygosity for the wildtype allele and negative immunostaining for the p27 protein. The patient was ascertained from a larger cohort of 37 patients, mostly Dutch, who were clinically suspected to have MEN but were negative for mutation in the MEN1 gene. The authors also studied 19 patients with familial acromegaly/pituitary adenomas and 50 Finnish patients with sporadic acromegaly who underwent direct sequencing of the CDKN1B gene; the Dutch woman was the only patient found to carry a CDKN1B mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17519308" 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 woman with MEN4, <a href="#4" class="mim-tip-reference" title="Molatore, S., Marinoni, I., Lee, M., Pulz, E., Ambrosio, M. R., degli Uberti, E. C., Zatelli, M. C., Pellegata, N. S. <strong>A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.</strong> Hum. Mutat. 31: E1825-E1835, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20824794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20824794</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20824794[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20824794">Molatore et al. (2010)</a> identified a heterozygous missense mutation in the CDKN1B gene (P69L; <a href="/entry/600778#0003">600778.0003</a>). The mutation caused reduced mutant protein levels due to more rapid degradation, had slightly higher cytoplasmic localization compared to wildtype, and lost the ability to bind CDK2 (<a href="/entry/116953">116953</a>). The P69L mutant protein was less effective at suppressing growth of neuroendocrine tumor cells in vitro compared to wildtype. The findings suggested a tumor suppressor role for p27 in neuroendocrine cells. Patient bronchial carcinoid and parathyroid adenoma tissue showed decreased or even absent p27 protein expression, but loss of heterozygosity (LOH) for the wildtype CDKN1B allele was observed only in the carcinoid sample. The patient was 1 (3.7%) of 27 individuals with a MEN-like phenotype who was found to carry a CDKN1B mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20824794" 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 69-year-old Spanish woman with MEN4, <a href="#3" class="mim-tip-reference" title="Malanga, D., De Gisi, S., Riccardi, M., Scrima, M., De Marco, C., Robledo, M., Viglietto, G. <strong>Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with multiple endocrine neoplasia-like phenotype.</strong> Europ. J. Endocr. 166: 551-560, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22129891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22129891</a>] [<a href="https://doi.org/10.1530/EJE-11-0929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22129891">Malanga et al. (2012)</a> identified a heterozygous mutation in the CDKN1B gene (<a href="/entry/600778#0004">600778.0004</a>). In vitro functional expression studies using a luciferase reporter in HeLa cells showed that the mutation resulted in a significant reduction (30-60%) in transcription and possibly translation. Patient peripheral blood cells showed a significant 3-fold decrease in CDKN1B mRNA levels compared to controls, consistent with haploinsufficiency. The patient was 1 of 15 Spanish individuals with MEN-like features who underwent direct sequencing of the CDKN1B gene and was the only patient found to carry a mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22129891" 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 62-year-old woman with MEN4, <a href="#5" class="mim-tip-reference" title="Occhi, G., Regazzo, D., Trivellin, G., Boaretto, F., Ciato, D., Bobisse, S., Ferasin, S., Cetani, F., Pardi, E., Korbonits, M., Pellegata, N. S., Sidarovich, V., Quattrone, A., Opocher, G., Mantero, F., Scaroni, C. <strong>A novel mutation in the upstream open reading frame of the CDKN1B gene causes a MEN4 phenotype.</strong> PLoS Genet. 9: e1003350, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23555276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23555276</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23555276[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1003350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23555276">Occhi et al. (2013)</a> identified a heterozygous 4-bp deletion in the 5-prime untranslated region of the CDKN1B gene (<a href="/entry/600778#0005">600778.0005</a>). The deletion affected the upstream open reading frame and was demonstrated to cause impaired translation by affecting translation reinitiation. Patient cells showed normal levels of mutant mRNA, but decreased expression of the p27 protein, with weak cytoplasmic staining. Pancreatic tumor cells from the patient showed weak cytoplasmic p27 staining; there was no LOH for the wildtype allele. The patient was 1 of 25 patients with MEN-related features who underwent direct sequencing of the CDKN1B gene and was the only one found to carry a mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23555276" 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 53-year-old Italian woman with MEN4, <a href="#7" class="mim-tip-reference" title="Tonelli, F., Giudici, F., Giusti, F., Marini, F., Cianferotti, L., Nesi, G., Brandi, M. L. <strong>A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.</strong> Europ. J. Endocr. 171: K7-K17, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24819502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24819502</a>] [<a href="https://doi.org/10.1530/EJE-14-0080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24819502">Tonelli et al. (2014)</a> identified a heterozygous truncating mutation in the CDKN1B gene (<a href="/entry/600778#0006">600778.0006</a>). Analysis of the patient's hyperplastic parathyroid tissue showed reduced nuclear p27 staining, but there was no LOH of the wildtype CDKN1B allele. The patient's asymptomatic 35-year-old son also carried the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24819502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Fritz, A., Walch, A., Piotrowska, K., Rosemann, M., Schaffer, E., Weber, K., Timper, A., Wildner, G., Graw, J., Hofler, H., Atkinson, M. J. <strong>Recessive transmission of a multiple endocrine neoplasia syndrome in the rat.</strong> Cancer Res. 62: 3048-3051, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12036912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12036912</a>]" pmid="12036912">Fritz et al. (2002)</a> described an MEN-like autosomal recessive disorder in the rat. Animals exhibiting the mutant phenotype developed multiple neuroendocrine malignancies within the first year of life, including bilateral adrenal pheochromocytoma, multiple extraadrenal pheochromocytoma, bilateral medullary thyroid cell neoplasia, bilateral parathyroid hyperplasia, and pituitary adenoma. The appearance of neoplastic disease was preceded by the development of bilateral juvenile cataracts. Although the spectrum of affected tissues was reminiscent of human forms of MEN, no germline mutations were detected in the RET (<a href="/entry/164761">164761</a>) or MEN1 genes. Segregation studies in F1 and F2 crosses yielded frequencies of affected animals consistent with an autosomal recessive mode of inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12036912" 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 rats with an MEN-like syndrome (Menx), with phenotypic overlap of MEN1 and MEN2A (<a href="/entry/171400">171400</a>), <a href="#6" class="mim-tip-reference" title="Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., Hofler, H., Fend, F., Graw, J., Atkinson, M. J. <strong>Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans.</strong> Proc. Nat. Acad. Sci. 103: 15558-15563, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 19213 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17030811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17030811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17030811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0603877103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17030811">Pellegata et al. (2006)</a> performed linkage analysis and identified a locus in a 4-Mb segment on rat chromosome 4, which includes the Cdkn1b gene. Sequencing revealed a homozygous frameshift mutation in the Cdkn1b gene resulting in a dramatic reduction of p27(Kip1) protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17030811" 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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Fritz, A., Walch, A., Piotrowska, K., Rosemann, M., Schaffer, E., Weber, K., Timper, A., Wildner, G., Graw, J., Hofler, H., Atkinson, M. J.
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<strong>Recessive transmission of a multiple endocrine neoplasia syndrome in the rat.</strong>
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Cancer Res. 62: 3048-3051, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12036912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12036912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12036912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Georgitsi, M., Raitila, A., Karhu, A., van der Luijt, R. B., Aalfs, C. M., Sane, T., Vierimaa, O., Makinen, M. J., Tuppurainen, K., Paschke, R., Gimm, O., Koch, C. A., and 11 others.
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<strong>Germline CDKN1B/p27(Kip1) mutation in multiple endocrine neoplasia.</strong>
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J. Clin. Endocr. Metab. 92: 3321-3325, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17519308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17519308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17519308" 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/10.1210/jc.2006-2843" target="_blank">Full Text</a>]
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Malanga, D., De Gisi, S., Riccardi, M., Scrima, M., De Marco, C., Robledo, M., Viglietto, G.
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<strong>Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with multiple endocrine neoplasia-like phenotype.</strong>
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Europ. J. Endocr. 166: 551-560, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22129891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22129891</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22129891" 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/10.1530/EJE-11-0929" target="_blank">Full Text</a>]
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Molatore, S., Marinoni, I., Lee, M., Pulz, E., Ambrosio, M. R., degli Uberti, E. C., Zatelli, M. C., Pellegata, N. S.
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<strong>A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.</strong>
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Hum. Mutat. 31: E1825-E1835, 2010. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20824794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20824794</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20824794[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20824794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.21354" target="_blank">Full Text</a>]
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Occhi, G., Regazzo, D., Trivellin, G., Boaretto, F., Ciato, D., Bobisse, S., Ferasin, S., Cetani, F., Pardi, E., Korbonits, M., Pellegata, N. S., Sidarovich, V., Quattrone, A., Opocher, G., Mantero, F., Scaroni, C.
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<strong>A novel mutation in the upstream open reading frame of the CDKN1B gene causes a MEN4 phenotype.</strong>
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PLoS Genet. 9: e1003350, 2013. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23555276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23555276</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23555276[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23555276" 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/10.1371/journal.pgen.1003350" target="_blank">Full Text</a>]
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Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., Hofler, H., Fend, F., Graw, J., Atkinson, M. J.
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<strong>Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans.</strong>
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Proc. Nat. Acad. Sci. 103: 15558-15563, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 19213 only, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17030811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17030811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17030811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17030811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0603877103" target="_blank">Full Text</a>]
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Tonelli, F., Giudici, F., Giusti, F., Marini, F., Cianferotti, L., Nesi, G., Brandi, M. L.
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<strong>A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.</strong>
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Europ. J. Endocr. 171: K7-K17, 2014. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24819502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24819502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24819502" 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/10.1530/EJE-14-0080" target="_blank">Full Text</a>]
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Marla J. F. O'Neill : 2/12/2007
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carol : 08/02/2017
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carol : 03/10/2015<br>mcolton : 3/10/2015<br>mcolton : 3/10/2015<br>ckniffin : 3/10/2015<br>carol : 9/19/2013<br>carol : 2/9/2011<br>carol : 5/3/2007<br>wwang : 2/12/2007
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<strong>#</strong> 610755
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MULTIPLE ENDOCRINE NEOPLASIA, TYPE IV; MEN4
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<strong>SNOMEDCT:</strong> 715907003;
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<strong>ORPHA:</strong> 276152;
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<strong>DO:</strong> 0080137;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus <br /> MIM number
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12p13.1
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Multiple endocrine neoplasia, type IV
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610755
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Autosomal dominant
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3
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CDKN1B
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600778
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<p>A number sign (#) is used with this entry because of evidence that multiple endocrine neoplasia type IV (MEN4) is caused by heterozygous mutation in the CDKN1B gene (600778) on chromosome 12p13.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of multiple endocrine neoplasia, see MEN1 (131100).</p>
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<strong>Clinical Features</strong>
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<p>Pellegata et al. (2006) reported a 3-generation family with what appeared to be MEN1-related tumors. The proband was a 48-year-old Caucasian female who developed acromegaly and had a 3-cm pituitary tumor removed at age 30. Histology revealed an invasive pituitary adenoma with growth hormone hyperproduction, high mitotic activity, and cell atypia. At age 46, she was diagnosed with primary hyperparathyroidism; at the time of study, she had not yet undergone surgery. Her deceased father had acromegaly, and a brother died at age 39 from hypertension. Her older sister was diagnosed at 55 years of age with renal angiomyolipoma and that sister's son developed testicular cancer at 28 years of age. </p><p>Georgitsi et al. (2007) reported a Dutch woman with MEN4 who developed small-cell neuroendocrine cervical carcinoma, an ACTH-secreting pituitary adenoma, and hyperparathyroidism in her forties. She was also diagnosed with multiple sclerosis. She had no family history of endocrine tumors. </p><p>Molatore et al. (2010) reported a 79-year-old Caucasian woman with bronchial carcinoid tumor, a nonfunctioning pituitary microadenoma, parathyroid adenoma, and papillary thyroid carcinoma. She also had type 2 diabetes mellitus. She had no family history of endocrine tumors. </p><p>Malanga et al. (2012) reported a 69-year-old Spanish woman with MEN4 manifest as gastric carcinoid tumor and hyperparathyroidism; there was no family history of endocrine neoplasia. </p><p>Tonelli et al. (2014) reported a 53-year-old Italian woman with persistent hyperparathyroidism due to parathyroid adenomas and gastrointestinal neuroendocrine tumors; she also had a history of hypothyroidism due to Hashimoto thyroiditis. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of MEN4 in the family reported by Pellegata et al. (2006) was consistent with autosomal dominant inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>In a 48-year-old Caucasian female with primary hyperparathyroidism and a history of pituitary adenoma (MEN4), Pellegata et al. (2006) identified a nonsense mutation in the CDKN1B gene (600778.0001). The mutation was also identified in her older sister who had renal angiomyolipoma, and in her youngest sister and that sister's teenaged daughter, who reported no symptoms but did not undergo thorough examination. Samples from a nephew with testicular cancer at age 28 and from her deceased father, who had acromegaly, were not available for analysis. The mutation was not found in 380 unrelated healthy controls. No mutations in the MEN1 gene (613733) were found in the proband or her older sister. </p><p>In a Dutch woman with MEN4, Georgitsi et al. (2007) identified a heterozygous truncating mutation in the CDKN1B gene (600778.0002). Tumor tissue from the patient's cervical carcinoma showed loss of heterozygosity for the wildtype allele and negative immunostaining for the p27 protein. The patient was ascertained from a larger cohort of 37 patients, mostly Dutch, who were clinically suspected to have MEN but were negative for mutation in the MEN1 gene. The authors also studied 19 patients with familial acromegaly/pituitary adenomas and 50 Finnish patients with sporadic acromegaly who underwent direct sequencing of the CDKN1B gene; the Dutch woman was the only patient found to carry a CDKN1B mutation. </p><p>In a woman with MEN4, Molatore et al. (2010) identified a heterozygous missense mutation in the CDKN1B gene (P69L; 600778.0003). The mutation caused reduced mutant protein levels due to more rapid degradation, had slightly higher cytoplasmic localization compared to wildtype, and lost the ability to bind CDK2 (116953). The P69L mutant protein was less effective at suppressing growth of neuroendocrine tumor cells in vitro compared to wildtype. The findings suggested a tumor suppressor role for p27 in neuroendocrine cells. Patient bronchial carcinoid and parathyroid adenoma tissue showed decreased or even absent p27 protein expression, but loss of heterozygosity (LOH) for the wildtype CDKN1B allele was observed only in the carcinoid sample. The patient was 1 (3.7%) of 27 individuals with a MEN-like phenotype who was found to carry a CDKN1B mutation. </p><p>In a 69-year-old Spanish woman with MEN4, Malanga et al. (2012) identified a heterozygous mutation in the CDKN1B gene (600778.0004). In vitro functional expression studies using a luciferase reporter in HeLa cells showed that the mutation resulted in a significant reduction (30-60%) in transcription and possibly translation. Patient peripheral blood cells showed a significant 3-fold decrease in CDKN1B mRNA levels compared to controls, consistent with haploinsufficiency. The patient was 1 of 15 Spanish individuals with MEN-like features who underwent direct sequencing of the CDKN1B gene and was the only patient found to carry a mutation. </p><p>In a 62-year-old woman with MEN4, Occhi et al. (2013) identified a heterozygous 4-bp deletion in the 5-prime untranslated region of the CDKN1B gene (600778.0005). The deletion affected the upstream open reading frame and was demonstrated to cause impaired translation by affecting translation reinitiation. Patient cells showed normal levels of mutant mRNA, but decreased expression of the p27 protein, with weak cytoplasmic staining. Pancreatic tumor cells from the patient showed weak cytoplasmic p27 staining; there was no LOH for the wildtype allele. The patient was 1 of 25 patients with MEN-related features who underwent direct sequencing of the CDKN1B gene and was the only one found to carry a mutation. </p><p>In a 53-year-old Italian woman with MEN4, Tonelli et al. (2014) identified a heterozygous truncating mutation in the CDKN1B gene (600778.0006). Analysis of the patient's hyperplastic parathyroid tissue showed reduced nuclear p27 staining, but there was no LOH of the wildtype CDKN1B allele. The patient's asymptomatic 35-year-old son also carried the mutation. </p>
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<strong>Animal Model</strong>
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<p>Fritz et al. (2002) described an MEN-like autosomal recessive disorder in the rat. Animals exhibiting the mutant phenotype developed multiple neuroendocrine malignancies within the first year of life, including bilateral adrenal pheochromocytoma, multiple extraadrenal pheochromocytoma, bilateral medullary thyroid cell neoplasia, bilateral parathyroid hyperplasia, and pituitary adenoma. The appearance of neoplastic disease was preceded by the development of bilateral juvenile cataracts. Although the spectrum of affected tissues was reminiscent of human forms of MEN, no germline mutations were detected in the RET (164761) or MEN1 genes. Segregation studies in F1 and F2 crosses yielded frequencies of affected animals consistent with an autosomal recessive mode of inheritance. </p><p>In rats with an MEN-like syndrome (Menx), with phenotypic overlap of MEN1 and MEN2A (171400), Pellegata et al. (2006) performed linkage analysis and identified a locus in a 4-Mb segment on rat chromosome 4, which includes the Cdkn1b gene. Sequencing revealed a homozygous frameshift mutation in the Cdkn1b gene resulting in a dramatic reduction of p27(Kip1) protein. </p>
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<strong>REFERENCES</strong>
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Fritz, A., Walch, A., Piotrowska, K., Rosemann, M., Schaffer, E., Weber, K., Timper, A., Wildner, G., Graw, J., Hofler, H., Atkinson, M. J.
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<strong>Recessive transmission of a multiple endocrine neoplasia syndrome in the rat.</strong>
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Cancer Res. 62: 3048-3051, 2002.
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[PubMed: 12036912]
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Georgitsi, M., Raitila, A., Karhu, A., van der Luijt, R. B., Aalfs, C. M., Sane, T., Vierimaa, O., Makinen, M. J., Tuppurainen, K., Paschke, R., Gimm, O., Koch, C. A., and 11 others.
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<strong>Germline CDKN1B/p27(Kip1) mutation in multiple endocrine neoplasia.</strong>
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J. Clin. Endocr. Metab. 92: 3321-3325, 2007.
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[PubMed: 17519308]
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[Full Text: https://doi.org/10.1210/jc.2006-2843]
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Malanga, D., De Gisi, S., Riccardi, M., Scrima, M., De Marco, C., Robledo, M., Viglietto, G.
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<strong>Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with multiple endocrine neoplasia-like phenotype.</strong>
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Europ. J. Endocr. 166: 551-560, 2012.
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[PubMed: 22129891]
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[Full Text: https://doi.org/10.1530/EJE-11-0929]
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Molatore, S., Marinoni, I., Lee, M., Pulz, E., Ambrosio, M. R., degli Uberti, E. C., Zatelli, M. C., Pellegata, N. S.
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<strong>A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.</strong>
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Hum. Mutat. 31: E1825-E1835, 2010. Note: Electronic Article.
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[PubMed: 20824794]
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[Full Text: https://doi.org/10.1002/humu.21354]
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Occhi, G., Regazzo, D., Trivellin, G., Boaretto, F., Ciato, D., Bobisse, S., Ferasin, S., Cetani, F., Pardi, E., Korbonits, M., Pellegata, N. S., Sidarovich, V., Quattrone, A., Opocher, G., Mantero, F., Scaroni, C.
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<strong>A novel mutation in the upstream open reading frame of the CDKN1B gene causes a MEN4 phenotype.</strong>
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PLoS Genet. 9: e1003350, 2013. Note: Electronic Article.
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[PubMed: 23555276]
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[Full Text: https://doi.org/10.1371/journal.pgen.1003350]
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Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., Hofler, H., Fend, F., Graw, J., Atkinson, M. J.
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<strong>Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans.</strong>
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Proc. Nat. Acad. Sci. 103: 15558-15563, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 19213 only, 2006.
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[PubMed: 17030811]
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[Full Text: https://doi.org/10.1073/pnas.0603877103]
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Tonelli, F., Giudici, F., Giusti, F., Marini, F., Cianferotti, L., Nesi, G., Brandi, M. L.
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<strong>A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.</strong>
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Europ. J. Endocr. 171: K7-K17, 2014. Note: Electronic Article.
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[PubMed: 24819502]
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[Full Text: https://doi.org/10.1530/EJE-14-0080]
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Contributors:
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/10/2015
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Creation Date:
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Marla J. F. O'Neill : 2/12/2007
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