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<title>
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Entry
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- #619101 - MISMATCH REPAIR CANCER SYNDROME 4; MMRCS4
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- OMIM
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<span class="h4">#619101</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/619101"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS276300"> <strong>Phenotypic Series</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#creationDate"><strong>Creation Date</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=(MISMATCH REPAIR CANCER SYNDROME) OR (PMS2)" class="mim-tip-hint" title="Clinical Trials" 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=19731&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/gtr/all/tests/?term=619101[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=252202" 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>
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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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</span>
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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>ORPHA:</strong> 252202<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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619101
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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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MISMATCH REPAIR CANCER SYNDROME 4; MMRCS4
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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="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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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/7/51?start=-3&limit=10&highlight=51">
|
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7p22.1
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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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Mismatch repair cancer syndrome 4
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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/619101"> 619101 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
|
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PMS2
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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/600259"> 600259 </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 class="btn-group ">
|
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<a href="/clinicalSynopsis/619101" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS276300" 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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/619101" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/619101" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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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> ABDOMEN </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Gastrointestinal </em>
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</span>
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
|
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|
|
- Adenomatous colonic polyps <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/428054006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">428054006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0850572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0850572</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> SKIN, NAILS, & HAIR </strong>
|
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</span>
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<em> Skin </em>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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|
|
- Cafe-au-lait spots <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/201281002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">201281002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L81.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L81.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221263&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221263</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000957</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000957</a>]</span><br /> -
|
|
Axillary freckling <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860335&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860335</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000997" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000997</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000997" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000997</a>]</span><br />
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|
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</span>
|
|
</div>
|
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
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</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
|
|
|
|
- Agenesis of the corpus callosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5102002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5102002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0175754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0175754</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span><br /> -
|
|
Gray matter heterotopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253150002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253150002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/448041008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">448041008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266491&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266491</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002282" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002282</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002282" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002282</a>]</span><br /> -
|
|
Interhemispheric cyst <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853188&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853188</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032327</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032327</a>]</span><br />
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|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
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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">
|
|
<strong> IMMUNOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Immunoglobulin class switch recombination deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542990</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 />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
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</div>
|
|
|
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|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Astrocytoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1157043006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1157043006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004114</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009592" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009592</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009592" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009592</a>]</span><br /> -
|
|
Glioblastoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1163375002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1163375002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/393563007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">393563007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017636</a>, <a href="https://bioportal.bioontology.org/search?q=C1621958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1621958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012174" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012174</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012174" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012174</a>]</span><br /> -
|
|
Oligodendroglioma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156974002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156974002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/443936004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">443936004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028945&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028945</a>, <a href="https://bioportal.bioontology.org/search?q=C0751396&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751396</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033681" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033681</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033681" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033681</a>]</span><br /> -
|
|
Neuroblastoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87364003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87364003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432328008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432328008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700095&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700095</a>, <a href="https://bioportal.bioontology.org/search?q=C0027819&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027819</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003006</a>]</span><br /> -
|
|
Supratentorial primitive neuroectodermal tumor (SPNET) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542991</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39781001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39781001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/699318007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">699318007</a>]</span><br /> -
|
|
Mucoepidermoid cancer of the parotid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542992&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542992</a>]</span><br /> -
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Colorectal adenocarcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/408645001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">408645001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1319315&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1319315</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040275</a>]</span><br /> -
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Ovarian neuroectodermal tumor <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542993&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542993</a>]</span><br /> -
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Endometrial adenocarcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123845008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123845008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/309245001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">309245001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1153706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1153706</a>]</span><br /> -
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Leukemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/93143009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">93143009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1162768007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1162768007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C95" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C95</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C95.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C95.90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C95.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C95.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/208.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">208.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/208" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">208</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023418</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001909" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001909</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001909" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001909</a>]</span><br /> -
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Lymphoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1163043007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1163043007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/188676008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">188676008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/118600007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">118600007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C85.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C85.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024299&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024299</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002665" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002665</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002665" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002665</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> LABORATORY ABNORMALITIES </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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- Elevated IgM <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239990</a>]</span><br /> -
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Decreased IgG2 and IgG4 <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542994</a>]</span><br /> -
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Decreased IgA <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29260007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29260007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162538&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162538</a>, <a href="https://bioportal.bioontology.org/search?q=C0553533&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0553533</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002720" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002720</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002720" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002720</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the PMS1 homolog 2, mismatch repair system component gene (PMS2, <a href="/entry/600259#0001">600259.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
|
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<h5>
|
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Mismatch repair cancer syndrome
|
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- <a href="/phenotypicSeries/PS276300">PS276300</a>
|
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- 4 Entries
|
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</h5>
|
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
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<thead>
|
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<tr>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Location</strong>
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</th>
|
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
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<strong>Phenotype</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Inheritance</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />mapping key</strong>
|
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />MIM number</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Gene/Locus</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/2/239?start=-3&limit=10&highlight=239"> 2p21-p16.3 </a>
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|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/619096"> Mismatch repair cancer syndrome 2 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/619096"> 619096 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/609309"> MSH2 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/609309"> 609309 </a>
|
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</span>
|
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</td>
|
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/2/245?start=-3&limit=10&highlight=245"> 2p16.3 </a>
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|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/619097"> Mismatch repair cancer syndrome 3 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/619097"> 619097 </a>
|
|
</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/600678"> MSH6 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/600678"> 600678 </a>
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
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|
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<a href="/geneMap/3/163?start=-3&limit=10&highlight=163"> 3p22.2 </a>
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/276300"> Mismatch repair cancer syndrome 1 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/276300"> 276300 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/120436"> MLH1 </a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/120436"> 120436 </a>
|
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</span>
|
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</td>
|
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</tr>
|
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<tr>
|
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<td>
|
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<span class="mim-font">
|
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|
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<a href="/geneMap/7/51?start=-3&limit=10&highlight=51"> 7p22.1 </a>
|
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|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/619101"> Mismatch repair cancer syndrome 4 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
|
</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/619101"> 619101 </a>
|
|
</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/600259"> PMS2 </a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/600259"> 600259 </a>
|
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</span>
|
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</td>
|
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</tr>
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|
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</tbody>
|
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</table>
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</div>
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<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
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</div>
|
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that mismatch repair cancer syndrome-4 (MMRCS4) is caused by homozygous or compound heterozygous mutation in the PMS2 gene (<a href="/entry/600259">600259</a>) on chromosome 7p22.</p>
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</span>
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<div>
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<p>Mismatch repair cancer syndrome-4 (MMRCS4) is an autosomal recessive childhood cancer predisposition syndrome characterized by early-onset leukemia/lymphoma, brain tumors, colorectal/gastrointestinal cancers, and other rare malignancies, including rhabdomyosarcoma (summary by <a href="#11" class="mim-tip-reference" title="Li, L., Hamel, N., Baker, K., McGuffin, M. J., Couillard, M., Gologan, A., Marcus, V. A., Chodirker, B., Chudley, A., Stefanovici, C., Durandy, A., Hegele, R. A., and 10 others. <strong>A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.</strong> J. Med. Genet. 52: 348-352, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25691505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25691505</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25691505">Li et al., 2015</a>). Cafe-au-lait spots are usually present (<a href="#4" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Charlton, R., Taylor, G. R., Glaser, A. W., Picton, S., Cole, T. R., Maher, E. R., McKeown, C. M. E., Mann, J. R., Yates, J. R., Baralle, D., Rankin, J., Bonthron, D. T., Sheridan, E. <strong>PMS2 mutations in childhood cancer.</strong> J. Nat. Cancer Inst. 98: 358-361, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16507833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16507833</a>] [<a href="https://doi.org/10.1093/jnci/djj073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16507833">De Vos et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16507833+25691505" 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 discussion of genetic heterogeneity of mismatch repair cancer syndrome, see MMRCS1 (<a href="/entry/276300">276300</a>).</p>
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<p><a href="#8" class="mim-tip-reference" title="Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W. <strong>The molecular basis of Turcot's syndrome.</strong> New Eng. J. Med. 332: 839-847, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7661930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7661930</a>] [<a href="https://doi.org/10.1056/NEJM199503303321302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7661930">Hamilton et al. (1995)</a> studied a family (family 12) with colonic adenomas in which 2 sibs had glioblastoma and cafe-au-lait spots, respectively. The 18-year-old male patient had had 2 colonic adenomas and 1 hyperplastic polyp by the time of total abdominal colectomy at age 13 years. He had non-Hodgkin lymphoma of the rectum at age 17 years. His sister had rectal carcinoma at age 11 years with only 3 adenomas of the sigmoid colon and rectum. Phenotypic adenomatous polyposis developed at age 14 years, for which she underwent total colectomy. In all, <a href="#8" class="mim-tip-reference" title="Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W. <strong>The molecular basis of Turcot's syndrome.</strong> New Eng. J. Med. 332: 839-847, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7661930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7661930</a>] [<a href="https://doi.org/10.1056/NEJM199503303321302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7661930">Hamilton et al. (1995)</a> analyzed 14 families with the clinical designation of 'Turcot syndrome' identified in 2 registries. Tissue samples from patients with mismatch repair (MMR) mutations showed DNA replication errors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7661930" 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="De Rosa, M., Fasano, C., Panariello, L., Scarano, M. I., Belli, G., Iannelli, A., Ciciliano, F., Izzo, P. <strong>Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.</strong> Oncogene 19: 1719-1723, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10763829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10763829</a>] [<a href="https://doi.org/10.1038/sj.onc.1203447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10763829">De Rosa et al. (2000)</a> reported 2 sisters with MMRCS4 and early-onset brain tumors. The proband presented with oligodendroglioma which was removed at age 14 years and recurred 3 years later. At age 18 years she was found to have developed colon carcinoma and died a few months after hemicolectomy. Her sister had a neuroblastoma at age 13 years and died at the age of 14 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10763829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Trimbath, J. D., Petersen, G. M., Erdman, S. H., Ferre, M., Luce, M. C., Giardiello, F. M. <strong>Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?</strong> Fam. Cancer 1: 101-105, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574005</a>] [<a href="https://doi.org/10.1023/a:1013881832014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574005">Trimbath et al. (2001)</a> described a 16-year-old Guyanese girl who presented with colorectal adenocarcinoma. She had 6 cafe-au-lait spots but no Lisch nodules or other signs of neurofibromatosis. At age 21 she developed a left ovarian neuroectodermal tumor and at age 23 she had endometrial carcinoma of the uterus and ovary. At age 24 she had a brain tumor. Her half sister developed anaplastic astrocytoma at age 7 years and 3 adenomatous polyps by the age of 20 years. The patient's half brother died of acute lymphoblastic leukemia at age 4 years. Both of these half sibs had multiple cafe-au-lait spots. The patient's paternal grandmother died of colorectal adenocarcinoma at age 53. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Picton, S., Sheridan, E., Bonthron, D. T. <strong>Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome.</strong> Am. J. Hum. Genet. 74: 954-964, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15077197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15077197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15077197[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/10.1086/420796" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15077197">De Vos et al. (2004)</a> reported a consanguineous family in which 3 sibs had early onset of brain tumors, 1 with a high-grade non-Hodgkin lymphoma and 2 with supratentorial primitive neuroectodermal tumors (SPNET), an aggressive embryonal tumor most likely derived from primitive neuroepithelial cells. All children also had cafe-au-lait spots, but no other features of NF1. No other family members had cancer, and examination of 2 of the children at young ages showed no bowel lesions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15077197" 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="De Vos, M., Hayward, B. E., Charlton, R., Taylor, G. R., Glaser, A. W., Picton, S., Cole, T. R., Maher, E. R., McKeown, C. M. E., Mann, J. R., Yates, J. R., Baralle, D., Rankin, J., Bonthron, D. T., Sheridan, E. <strong>PMS2 mutations in childhood cancer.</strong> J. Nat. Cancer Inst. 98: 358-361, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16507833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16507833</a>] [<a href="https://doi.org/10.1093/jnci/djj073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16507833">De Vos et al. (2006)</a> studied 13 patients with MMRCS4 from 6 consanguineous families of Pakistani origin. Ten of the 13 had cafe-au-lait spots; no information was available for the remaining 3 patients. <a href="#4" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Charlton, R., Taylor, G. R., Glaser, A. W., Picton, S., Cole, T. R., Maher, E. R., McKeown, C. M. E., Mann, J. R., Yates, J. R., Baralle, D., Rankin, J., Bonthron, D. T., Sheridan, E. <strong>PMS2 mutations in childhood cancer.</strong> J. Nat. Cancer Inst. 98: 358-361, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16507833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16507833</a>] [<a href="https://doi.org/10.1093/jnci/djj073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16507833">De Vos et al. (2006)</a> noted that the cafe-au-lait spots or patches had a ragged-edged, slightly diffuse appearance that was not typical of the more sharply delineated cafe-au-lait spots typical of neurofibromatosis type I (NF1; <a href="/entry/162200">162200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16507833" 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="Auclair, J., Leroux, D., Desseigne, F., Lasset, C., Saurin, J. C., Joly, M. O., Pinson, S., Xu, X. L., Montmain, G., Ruano, E., Navarro, C., Puisieux, A., Wang, Q. <strong>Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation.</strong> Hum. Mutat. 28: 1084-1090, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17557300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17557300</a>] [<a href="https://doi.org/10.1002/humu.20569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17557300">Auclair et al. (2007)</a> reported a family (C01204) in which a girl developed oligodendroglioma at age 19 years and colonic adenocarcinoma at age 24 years. She died 1 year later from rapid malignant evolution. A sister developed colon cancer at age 20 years and endometrial cancer at age 24; she had isolated cafe-au-lait spots. The parents were unaffected, but there was a remote family history of colorectal cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17557300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Kratz, C. P., Niemeyer, C. M., Juttner, E., Kartal, M., Weninger, A., Schmitt-Graeff, A., Kontny, U., Lauten, M., Utzolino, S., Radecke, J., Fonatsch, C., Wimmer, K. <strong>Childhood T-cell non-Hodgkin's lymphoma, colorectal carcinoma and brain tumor in association with cafe-au-lait spots caused by a novel homozygous PMS2 mutation. (Letter)</strong> Leukemia 22: 1078-1080, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18007577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18007577</a>] [<a href="https://doi.org/10.1038/sj.leu.2405008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18007577">Kratz et al. (2008)</a> reported a Turkish girl with MMRCS4 who had been successfully treated for non-Hodgkin lymphoma at age 6 years and who presented at age 16 years with colorectal carcinomas. The patient's sister had cafe-au-lait spots and died from a supratentorial primitive neuroectodermal tumor at age 9 years. The parents and 4 sibs were healthy and without cancer history at time of report, although 1 sib also had cafe-au-lait spots. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18007577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Peron, S., Metin, A., Gardes, P., Alyanakian, M.-A., Sheridan, E., Kratz, C. P., Fischer, A., Durandy, A. <strong>Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination.</strong> J. Exp. Med. 205: 2465-2472, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18824584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18824584</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18824584[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20080789" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18824584">Peron et al. (2008)</a> reported a 12-year-old Turkish girl with MMRCS4 who exhibited Ig class switch recombination (CSR) deficiency. She presented with multiple cafe-au-lait spots and suffered from recurrent infections from the age of 1 year, leading to an immunodeficiency diagnosis at 9 years of age. A year later, she developed a colorectal adenocarcinoma. In vitro analysis showed that the CSR defect was characterized by the occurrence of double-strand DNA breaks in switch regions and abnormal formation of switch junctions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18824584" 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="Giunti, L., Cetica, V., Ricci, U., Giglio, S., Sardi, I., Paglierani, M., Andreucci, E., Sanzo, M., Forni, M., Buccoliero, A. M., Genitori, L., Genuardi, M. <strong>Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.</strong> Europ. J. Hum. Genet. 17: 919-927, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19156169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19156169</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19156169[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2008.271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19156169">Giunti et al. (2009)</a> studied a family in which a male patient (patient 121), the second born of 3 sibs, was diagnosed with high-grade glioma at age 10 years 3 months. The presence of multiple cafe-au-lait spots raised the suspicion of NF1. His younger sister died at the age of 4 years due to a brainstem malignancy of undetermined type. His elder sister (121S) was diagnosed with mucinous carcinoma of the ascending colon at the age of 21 years. Parents were healthy and unrelated, and family history was otherwise unremarkable, except for a maternal second cousin, who had died of leukemia at the age of 11 years, and his mother, who had a diagnosis of colorectal cancer at 28 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19156169" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Kratz, C. P., Holter, S., Etzler, J., Lauten, M., Pollett, A., Niemeyer, C. M., Gallinger, S., Wimmer, K. <strong>Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.</strong> J. Med. Genet. 46: 418-420, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19293170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19293170</a>] [<a href="https://doi.org/10.1136/jmg.2008.064212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19293170">Kratz et al. (2009)</a> reported a boy (family 1), born of consanguineous parents, who developed a rhabdomyosarcoma at age 3 years and a colonic adenocarcinoma at age 8. Two sibs in a second unrelated consanguineous family (family 2) developed multiple colonic adenocarcinomas, and an anaplastic astrocytoma and an undifferentiated sarcoma, respectively, associated with lack of PMS2 protein expression. The findings were consistent with biallelic germline PMS2 mutations, although genetic testing was not possible. Family history in both patients revealed multiple cases of cancer. The findings expanded the types of tumors associated with the mismatch repair cancer syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19293170" 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="Baas, A. F., Gabbett, M., Rimac, M., Kansikas, M., Raphael, M., Nievelstein, R. A. J., Nicholls, W., Offerhaus, J., Bodmer, D., Wernstedt, A., Krabichler, B., Strasser, U., Nystrom, M., Zschocke, J., Robertson, S. P., van Haelst, M. M., Wimmer, K. <strong>Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.</strong> Europ. J. Hum. Genet. 21: 55-61, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22692065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22692065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22692065[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22692065">Baas et al. (2013)</a> reported 2 unrelated children with MMRCS4 and structural brain anomalies. A boy (patient 1), born of consanguineous parents, developed a B-cell non-Hodgkin lymphoma (NHL) at age 9 years. At age 11, he developed a mucoepidermoid carcinoma of the parotid gland, and 6 months later, he was diagnosed with a T-cell NHL. Brain MRI showed agenesis of the corpus callosum, an interhemispheric cyst, and several periventricular gray matter heterotopias. He also had multiple cafe-au-lait spots. Another patient (patient 3) was a boy who was noted to have dilation of the lateral ventricles on prenatal ultrasound and agenesis of the corpus callosum after birth. He developed an anaplastic astrocytoma of the spinal cord at age 2 years, 10 months. At age 5 years, he developed a T-lymphoblastic lymphoma, and died of sepsis during treatment 9 months later. Both of these patients had normal psychomotor development. <a href="#2" class="mim-tip-reference" title="Baas, A. F., Gabbett, M., Rimac, M., Kansikas, M., Raphael, M., Nievelstein, R. A. J., Nicholls, W., Offerhaus, J., Bodmer, D., Wernstedt, A., Krabichler, B., Strasser, U., Nystrom, M., Zschocke, J., Robertson, S. P., van Haelst, M. M., Wimmer, K. <strong>Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.</strong> Europ. J. Hum. Genet. 21: 55-61, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22692065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22692065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22692065[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22692065">Baas et al. (2013)</a> also described a third patient with MMRCS1 (<a href="/entry/276300">276300</a>) and structural brain anomalies whose psychomotor development was mildly delayed. <a href="#2" class="mim-tip-reference" title="Baas, A. F., Gabbett, M., Rimac, M., Kansikas, M., Raphael, M., Nievelstein, R. A. J., Nicholls, W., Offerhaus, J., Bodmer, D., Wernstedt, A., Krabichler, B., Strasser, U., Nystrom, M., Zschocke, J., Robertson, S. P., van Haelst, M. M., Wimmer, K. <strong>Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.</strong> Europ. J. Hum. Genet. 21: 55-61, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22692065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22692065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22692065[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22692065">Baas et al. (2013)</a> identified 1 other published report of a patient with MMRCS and agenesis of the corpus callosum (<a href="#7" class="mim-tip-reference" title="Gururangan, S., Frankel, W., Broaddus, R., Clendenning, M., Senter, L., McDonald, M., Eastwood, J., Reardon, D., Vredenburgh, J., Quinn, J., Friedman, H. S. <strong>Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation.</strong> Neuro Oncol. 10: 93-97, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17993636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17993636</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17993636[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/10.1215/15228517-2007-037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17993636">Gururangan et al., 2008</a>), and concluded that the prevalence of cerebral malformations associated with this syndrome may be as high as 6.6%, which is above the population birth prevalence of these malformations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17993636+22692065" 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 MMRCS4 in the family studied by <a href="#13" class="mim-tip-reference" title="Trimbath, J. D., Petersen, G. M., Erdman, S. H., Ferre, M., Luce, M. C., Giardiello, F. M. <strong>Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?</strong> Fam. Cancer 1: 101-105, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574005</a>] [<a href="https://doi.org/10.1023/a:1013881832014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574005">Trimbath et al. (2001)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574005" 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 family (family 12) with colonic adenomas, including 2 sibs with glioblastoma and cafe-au-lait spots, respectively, <a href="#8" class="mim-tip-reference" title="Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W. <strong>The molecular basis of Turcot's syndrome.</strong> New Eng. J. Med. 332: 839-847, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7661930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7661930</a>] [<a href="https://doi.org/10.1056/NEJM199503303321302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7661930">Hamilton et al. (1995)</a> identified a truncating mutation in the PMS2 gene (<a href="/entry/600259#0001">600259.0001</a>); a second PMS2 mutation (<a href="/entry/600249#0005">600249.0005</a>) was later identified in this family by <a href="#5" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Picton, S., Sheridan, E., Bonthron, D. T. <strong>Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome.</strong> Am. J. Hum. Genet. 74: 954-964, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15077197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15077197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15077197[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/10.1086/420796" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15077197">De Vos et al. (2004)</a>, indicating autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7661930+15077197" 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 girl who developed oligodendroglioma at age 14 years and colon carcinoma at age 18 years, <a href="#3" class="mim-tip-reference" title="De Rosa, M., Fasano, C., Panariello, L., Scarano, M. I., Belli, G., Iannelli, A., Ciciliano, F., Izzo, P. <strong>Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.</strong> Oncogene 19: 1719-1723, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10763829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10763829</a>] [<a href="https://doi.org/10.1038/sj.onc.1203447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10763829">De Rosa et al. (2000)</a> identified compound heterozygosity for mutations in the PMS2 gene (<a href="/entry/600259#0002">600259.0002</a>, <a href="/entry/600259#0003">600259.0003</a>). The girl's sister had died at age 14 of neuroblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10763829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a consanguineous Guyanese family with variable expression of colorectal adenocarcinoma, acute leukemia, brain tumors, and cafe-au-lait spots, <a href="#13" class="mim-tip-reference" title="Trimbath, J. D., Petersen, G. M., Erdman, S. H., Ferre, M., Luce, M. C., Giardiello, F. M. <strong>Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?</strong> Fam. Cancer 1: 101-105, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574005</a>] [<a href="https://doi.org/10.1023/a:1013881832014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574005">Trimbath et al. (2001)</a> identified a homozygous mutation in the PMS2 gene (<a href="/entry/600259#0013">600259.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a consanguineous family in which 3 sibs had early onset of brain tumors, but no colonic lesions, <a href="#5" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Picton, S., Sheridan, E., Bonthron, D. T. <strong>Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome.</strong> Am. J. Hum. Genet. 74: 954-964, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15077197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15077197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15077197[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/10.1086/420796" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15077197">De Vos et al. (2004)</a> identified a homozygous nonsense mutation in the PMS2 gene (R802X; <a href="/entry/600259#0004">600259.0004</a>). In affected members of 5 of 6 consanguineous Pakistani families with MMRCS4, <a href="#4" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Charlton, R., Taylor, G. R., Glaser, A. W., Picton, S., Cole, T. R., Maher, E. R., McKeown, C. M. E., Mann, J. R., Yates, J. R., Baralle, D., Rankin, J., Bonthron, D. T., Sheridan, E. <strong>PMS2 mutations in childhood cancer.</strong> J. Nat. Cancer Inst. 98: 358-361, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16507833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16507833</a>] [<a href="https://doi.org/10.1093/jnci/djj073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16507833">De Vos et al. (2006)</a> identified homozygosity for the R802X mutation. There was evidence of a founder effect. Affected members of the remaining family studied by <a href="#4" class="mim-tip-reference" title="De Vos, M., Hayward, B. E., Charlton, R., Taylor, G. R., Glaser, A. W., Picton, S., Cole, T. R., Maher, E. R., McKeown, C. M. E., Mann, J. R., Yates, J. R., Baralle, D., Rankin, J., Bonthron, D. T., Sheridan, E. <strong>PMS2 mutations in childhood cancer.</strong> J. Nat. Cancer Inst. 98: 358-361, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16507833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16507833</a>] [<a href="https://doi.org/10.1093/jnci/djj073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16507833">De Vos et al. (2006)</a> carried a homozygous tyr181-to-ter mutation (Y181X) resulting from a 1-bp deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16507833+15077197" 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 2 sibs from a family (C01204) with MMRCS4, <a href="#1" class="mim-tip-reference" title="Auclair, J., Leroux, D., Desseigne, F., Lasset, C., Saurin, J. C., Joly, M. O., Pinson, S., Xu, X. L., Montmain, G., Ruano, E., Navarro, C., Puisieux, A., Wang, Q. <strong>Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation.</strong> Hum. Mutat. 28: 1084-1090, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17557300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17557300</a>] [<a href="https://doi.org/10.1002/humu.20569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17557300">Auclair et al. (2007)</a> identified compound heterozygosity for 2 mutations in the PMS2 gene (<a href="/entry/600259#0011">600259.0011</a>, <a href="/entry/600259#0012">600259.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17557300" 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 12-year-old Turkish girl with colorectal adenocarcinoma and Ig class switch recombination (CSR) deficiency, <a href="#12" class="mim-tip-reference" title="Peron, S., Metin, A., Gardes, P., Alyanakian, M.-A., Sheridan, E., Kratz, C. P., Fischer, A., Durandy, A. <strong>Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination.</strong> J. Exp. Med. 205: 2465-2472, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18824584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18824584</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18824584[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20080789" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18824584">Peron et al. (2008)</a> identified homozygosity for a 4-exon deletion/18-bp insertion in the PMS2 gene (<a href="/entry/600259#0018">600259.0018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18824584" 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 boy (family 1) with MMRCS4, <a href="#9" class="mim-tip-reference" title="Kratz, C. P., Holter, S., Etzler, J., Lauten, M., Pollett, A., Niemeyer, C. M., Gallinger, S., Wimmer, K. <strong>Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.</strong> J. Med. Genet. 46: 418-420, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19293170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19293170</a>] [<a href="https://doi.org/10.1136/jmg.2008.064212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19293170">Kratz et al. (2009)</a> identified a homozygous mutation in the PMS2 gene (C73X; <a href="/entry/600259#0016">600259.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19293170" 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>Defects in the MMR genes are associated with microsatellite instability (MSI) in tumor DNA. One system classifies MSI into type A, defined by smaller allelic shifts, and type B, defined by comparatively larger allelic shifts. Using a 5-mononucleotide marker panel to analyze MSI, <a href="#6" class="mim-tip-reference" title="Giunti, L., Cetica, V., Ricci, U., Giglio, S., Sardi, I., Paglierani, M., Andreucci, E., Sanzo, M., Forni, M., Buccoliero, A. M., Genitori, L., Genuardi, M. <strong>Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.</strong> Europ. J. Hum. Genet. 17: 919-927, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19156169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19156169</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19156169[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2008.271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19156169">Giunti et al. (2009)</a> found that only 2 of 34 pediatric glioma tumor samples had unstable markers consistent with MSI. Both of these tumors were glioblastoma multiforme, and both patients had a family history of the mismatch repair cancer syndrome. Genetic analysis identified compound heterozygous mutations in the PMS2 gene in 1 patient (121S) and a heterozygous mutation in the MLH1 gene in the other; a second MLH1 mutation was not identified in the second patient. Both tumors showed small size shifts in the alleles compared to the constitutional DNA, with differences in the range of 1 to 2 bp. A colorectal tumor from 1 patient's affected sister showed the larger type B MSI. <a href="#6" class="mim-tip-reference" title="Giunti, L., Cetica, V., Ricci, U., Giglio, S., Sardi, I., Paglierani, M., Andreucci, E., Sanzo, M., Forni, M., Buccoliero, A. M., Genitori, L., Genuardi, M. <strong>Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.</strong> Europ. J. Hum. Genet. 17: 919-927, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19156169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19156169</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19156169[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2008.271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19156169">Giunti et al. (2009)</a> noted that colorectal cancers often have higher degrees of instability compared to gliomas, perhaps because of the higher cell turnover of intestinal cells compared to neurons. The findings suggested that the finding of type A MSI in pediatric gliomas may be an indicator of Turcot syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19156169" 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 13 patients from 7 unrelated Inuit families with an attenuated form of MMRCS, <a href="#11" class="mim-tip-reference" title="Li, L., Hamel, N., Baker, K., McGuffin, M. J., Couillard, M., Gologan, A., Marcus, V. A., Chodirker, B., Chudley, A., Stefanovici, C., Durandy, A., Hegele, R. A., and 10 others. <strong>A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.</strong> J. Med. Genet. 52: 348-352, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25691505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25691505</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25691505">Li et al. (2015)</a> identified a homozygous c.2002A-G transition in the PMS2 gene (<a href="/entry/600259#0019">600259.0019</a>). Analysis of patient cells showed that the mutation resulted in a splicing defect and nonsense-mediated mRNA decay, although there were minor amounts of full-length transcripts and some residual normal full-length functional protein. Haplotype analysis indicated a founder effect estimated to have appeared late in the 11th century. The authors estimated an allele frequency of 1 in 16 individuals in the Inuit population of Nunavik in northern Quebec. The age at cancer onset in individuals homozygous for the c.2002A-G mutation was significantly later (median age 22 years) compared to individuals homozygous for truncating PMS2 mutations (8 years). There was also a difference in the tumor spectrum, with brain tumors being significantly less prevalent in c.2002A-G homozygotes (15%) compared to truncating homozygotes (67%). However, 1 patient homozygous for the c.2002A-G mutation developed a primitive neuroectodermal tumor at age 3 years. <a href="#11" class="mim-tip-reference" title="Li, L., Hamel, N., Baker, K., McGuffin, M. J., Couillard, M., Gologan, A., Marcus, V. A., Chodirker, B., Chudley, A., Stefanovici, C., Durandy, A., Hegele, R. A., and 10 others. <strong>A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.</strong> J. Med. Genet. 52: 348-352, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25691505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25691505</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25691505">Li et al. (2015)</a> concluded that even a low level of PMS2 expression likely delays cancer onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25691505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Turcot1959" class="mim-tip-reference" title="Turcot, J., Despres, J.-P., St. Pierre, F. <strong>Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases.</strong> Dis. Colon Rectum 2: 465-468, 1959.">Turcot et al. (1959)</a>
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<strong>Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation.</strong>
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Hum. Mutat. 28: 1084-1090, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17557300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17557300</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17557300" 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.20569" target="_blank">Full Text</a>]
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Baas, A. F., Gabbett, M., Rimac, M., Kansikas, M., Raphael, M., Nievelstein, R. A. J., Nicholls, W., Offerhaus, J., Bodmer, D., Wernstedt, A., Krabichler, B., Strasser, U., Nystrom, M., Zschocke, J., Robertson, S. P., van Haelst, M. M., Wimmer, K.
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<strong>Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.</strong>
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Europ. J. Hum. Genet. 21: 55-61, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22692065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22692065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22692065[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=22692065" 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/ejhg.2012.117" target="_blank">Full Text</a>]
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De Rosa, M., Fasano, C., Panariello, L., Scarano, M. I., Belli, G., Iannelli, A., Ciciliano, F., Izzo, P.
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<strong>Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.</strong>
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Oncogene 19: 1719-1723, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10763829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10763829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10763829" 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/sj.onc.1203447" target="_blank">Full Text</a>]
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De Vos, M., Hayward, B. E., Charlton, R., Taylor, G. R., Glaser, A. W., Picton, S., Cole, T. R., Maher, E. R., McKeown, C. M. E., Mann, J. R., Yates, J. R., Baralle, D., Rankin, J., Bonthron, D. T., Sheridan, E.
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J. Nat. Cancer Inst. 98: 358-361, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16507833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16507833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16507833" 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/10.1093/jnci/djj073" target="_blank">Full Text</a>]
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De Vos, M., Hayward, B. E., Picton, S., Sheridan, E., Bonthron, D. T.
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<strong>Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome.</strong>
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Am. J. Hum. Genet. 74: 954-964, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15077197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15077197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15077197[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=15077197" 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/10.1086/420796" target="_blank">Full Text</a>]
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Giunti, L., Cetica, V., Ricci, U., Giglio, S., Sardi, I., Paglierani, M., Andreucci, E., Sanzo, M., Forni, M., Buccoliero, A. M., Genitori, L., Genuardi, M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19156169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19156169</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19156169[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=19156169" 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/ejhg.2008.271" target="_blank">Full Text</a>]
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Gururangan, S., Frankel, W., Broaddus, R., Clendenning, M., Senter, L., McDonald, M., Eastwood, J., Reardon, D., Vredenburgh, J., Quinn, J., Friedman, H. S.
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<strong>Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17993636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17993636</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17993636[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=17993636" 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/10.1215/15228517-2007-037" target="_blank">Full Text</a>]
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Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7661930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7661930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7661930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJM199503303321302" target="_blank">Full Text</a>]
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Kratz, C. P., Holter, S., Etzler, J., Lauten, M., Pollett, A., Niemeyer, C. M., Gallinger, S., Wimmer, K.
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<strong>Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19293170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19293170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19293170" 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/10.1136/jmg.2008.064212" target="_blank">Full Text</a>]
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Kratz, C. P., Niemeyer, C. M., Juttner, E., Kartal, M., Weninger, A., Schmitt-Graeff, A., Kontny, U., Lauten, M., Utzolino, S., Radecke, J., Fonatsch, C., Wimmer, K.
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<strong>Childhood T-cell non-Hodgkin's lymphoma, colorectal carcinoma and brain tumor in association with cafe-au-lait spots caused by a novel homozygous PMS2 mutation. (Letter)</strong>
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Leukemia 22: 1078-1080, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18007577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18007577</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18007577" 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/sj.leu.2405008" target="_blank">Full Text</a>]
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<a id="Li2015" class="mim-anchor"></a>
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Li, L., Hamel, N., Baker, K., McGuffin, M. J., Couillard, M., Gologan, A., Marcus, V. A., Chodirker, B., Chudley, A., Stefanovici, C., Durandy, A., Hegele, R. A., and 10 others.
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<strong>A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.</strong>
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J. Med. Genet. 52: 348-352, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25691505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25691505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25691505" 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/10.1136/jmedgenet-2014-102934" target="_blank">Full Text</a>]
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Peron, S., Metin, A., Gardes, P., Alyanakian, M.-A., Sheridan, E., Kratz, C. P., Fischer, A., Durandy, A.
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<strong>Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination.</strong>
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J. Exp. Med. 205: 2465-2472, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18824584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18824584</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18824584[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=18824584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1084/jem.20080789" target="_blank">Full Text</a>]
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Trimbath, J. D., Petersen, G. M., Erdman, S. H., Ferre, M., Luce, M. C., Giardiello, F. M.
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<strong>Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?</strong>
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Fam. Cancer 1: 101-105, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574005</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574005" 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/10.1023/a:1013881832014" target="_blank">Full Text</a>]
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Turcot, J., Despres, J.-P., St. Pierre, F.
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<strong>Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases.</strong>
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Dis. Colon Rectum 2: 465-468, 1959.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13839882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13839882</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13839882" 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/BF02616938" target="_blank">Full Text</a>]
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Creation Date:
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Anne M. Stumpf : 11/16/2020
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carol : 09/29/2023
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carol : 11/25/2020<br>alopez : 11/24/2020
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<strong>ORPHA:</strong> 252202;
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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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7p22.1
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Mismatch repair cancer syndrome 4
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619101
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Autosomal recessive
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3
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PMS2
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600259
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<p>A number sign (#) is used with this entry because of evidence that mismatch repair cancer syndrome-4 (MMRCS4) is caused by homozygous or compound heterozygous mutation in the PMS2 gene (600259) on chromosome 7p22.</p>
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<p>Mismatch repair cancer syndrome-4 (MMRCS4) is an autosomal recessive childhood cancer predisposition syndrome characterized by early-onset leukemia/lymphoma, brain tumors, colorectal/gastrointestinal cancers, and other rare malignancies, including rhabdomyosarcoma (summary by Li et al., 2015). Cafe-au-lait spots are usually present (De Vos et al., 2006). </p><p>For a discussion of genetic heterogeneity of mismatch repair cancer syndrome, see MMRCS1 (276300).</p>
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<strong>Clinical Features</strong>
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<p>Hamilton et al. (1995) studied a family (family 12) with colonic adenomas in which 2 sibs had glioblastoma and cafe-au-lait spots, respectively. The 18-year-old male patient had had 2 colonic adenomas and 1 hyperplastic polyp by the time of total abdominal colectomy at age 13 years. He had non-Hodgkin lymphoma of the rectum at age 17 years. His sister had rectal carcinoma at age 11 years with only 3 adenomas of the sigmoid colon and rectum. Phenotypic adenomatous polyposis developed at age 14 years, for which she underwent total colectomy. In all, Hamilton et al. (1995) analyzed 14 families with the clinical designation of 'Turcot syndrome' identified in 2 registries. Tissue samples from patients with mismatch repair (MMR) mutations showed DNA replication errors. </p><p>De Rosa et al. (2000) reported 2 sisters with MMRCS4 and early-onset brain tumors. The proband presented with oligodendroglioma which was removed at age 14 years and recurred 3 years later. At age 18 years she was found to have developed colon carcinoma and died a few months after hemicolectomy. Her sister had a neuroblastoma at age 13 years and died at the age of 14 years. </p><p>Trimbath et al. (2001) described a 16-year-old Guyanese girl who presented with colorectal adenocarcinoma. She had 6 cafe-au-lait spots but no Lisch nodules or other signs of neurofibromatosis. At age 21 she developed a left ovarian neuroectodermal tumor and at age 23 she had endometrial carcinoma of the uterus and ovary. At age 24 she had a brain tumor. Her half sister developed anaplastic astrocytoma at age 7 years and 3 adenomatous polyps by the age of 20 years. The patient's half brother died of acute lymphoblastic leukemia at age 4 years. Both of these half sibs had multiple cafe-au-lait spots. The patient's paternal grandmother died of colorectal adenocarcinoma at age 53. </p><p>De Vos et al. (2004) reported a consanguineous family in which 3 sibs had early onset of brain tumors, 1 with a high-grade non-Hodgkin lymphoma and 2 with supratentorial primitive neuroectodermal tumors (SPNET), an aggressive embryonal tumor most likely derived from primitive neuroepithelial cells. All children also had cafe-au-lait spots, but no other features of NF1. No other family members had cancer, and examination of 2 of the children at young ages showed no bowel lesions. </p><p>De Vos et al. (2006) studied 13 patients with MMRCS4 from 6 consanguineous families of Pakistani origin. Ten of the 13 had cafe-au-lait spots; no information was available for the remaining 3 patients. De Vos et al. (2006) noted that the cafe-au-lait spots or patches had a ragged-edged, slightly diffuse appearance that was not typical of the more sharply delineated cafe-au-lait spots typical of neurofibromatosis type I (NF1; 162200). </p><p>Auclair et al. (2007) reported a family (C01204) in which a girl developed oligodendroglioma at age 19 years and colonic adenocarcinoma at age 24 years. She died 1 year later from rapid malignant evolution. A sister developed colon cancer at age 20 years and endometrial cancer at age 24; she had isolated cafe-au-lait spots. The parents were unaffected, but there was a remote family history of colorectal cancer. </p><p>Kratz et al. (2008) reported a Turkish girl with MMRCS4 who had been successfully treated for non-Hodgkin lymphoma at age 6 years and who presented at age 16 years with colorectal carcinomas. The patient's sister had cafe-au-lait spots and died from a supratentorial primitive neuroectodermal tumor at age 9 years. The parents and 4 sibs were healthy and without cancer history at time of report, although 1 sib also had cafe-au-lait spots. </p><p>Peron et al. (2008) reported a 12-year-old Turkish girl with MMRCS4 who exhibited Ig class switch recombination (CSR) deficiency. She presented with multiple cafe-au-lait spots and suffered from recurrent infections from the age of 1 year, leading to an immunodeficiency diagnosis at 9 years of age. A year later, she developed a colorectal adenocarcinoma. In vitro analysis showed that the CSR defect was characterized by the occurrence of double-strand DNA breaks in switch regions and abnormal formation of switch junctions. </p><p>Giunti et al. (2009) studied a family in which a male patient (patient 121), the second born of 3 sibs, was diagnosed with high-grade glioma at age 10 years 3 months. The presence of multiple cafe-au-lait spots raised the suspicion of NF1. His younger sister died at the age of 4 years due to a brainstem malignancy of undetermined type. His elder sister (121S) was diagnosed with mucinous carcinoma of the ascending colon at the age of 21 years. Parents were healthy and unrelated, and family history was otherwise unremarkable, except for a maternal second cousin, who had died of leukemia at the age of 11 years, and his mother, who had a diagnosis of colorectal cancer at 28 years. </p><p>Kratz et al. (2009) reported a boy (family 1), born of consanguineous parents, who developed a rhabdomyosarcoma at age 3 years and a colonic adenocarcinoma at age 8. Two sibs in a second unrelated consanguineous family (family 2) developed multiple colonic adenocarcinomas, and an anaplastic astrocytoma and an undifferentiated sarcoma, respectively, associated with lack of PMS2 protein expression. The findings were consistent with biallelic germline PMS2 mutations, although genetic testing was not possible. Family history in both patients revealed multiple cases of cancer. The findings expanded the types of tumors associated with the mismatch repair cancer syndrome. </p><p>Baas et al. (2013) reported 2 unrelated children with MMRCS4 and structural brain anomalies. A boy (patient 1), born of consanguineous parents, developed a B-cell non-Hodgkin lymphoma (NHL) at age 9 years. At age 11, he developed a mucoepidermoid carcinoma of the parotid gland, and 6 months later, he was diagnosed with a T-cell NHL. Brain MRI showed agenesis of the corpus callosum, an interhemispheric cyst, and several periventricular gray matter heterotopias. He also had multiple cafe-au-lait spots. Another patient (patient 3) was a boy who was noted to have dilation of the lateral ventricles on prenatal ultrasound and agenesis of the corpus callosum after birth. He developed an anaplastic astrocytoma of the spinal cord at age 2 years, 10 months. At age 5 years, he developed a T-lymphoblastic lymphoma, and died of sepsis during treatment 9 months later. Both of these patients had normal psychomotor development. Baas et al. (2013) also described a third patient with MMRCS1 (276300) and structural brain anomalies whose psychomotor development was mildly delayed. Baas et al. (2013) identified 1 other published report of a patient with MMRCS and agenesis of the corpus callosum (Gururangan et al., 2008), and concluded that the prevalence of cerebral malformations associated with this syndrome may be as high as 6.6%, which is above the population birth prevalence of these malformations. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of MMRCS4 in the family studied by Trimbath et al. (2001) was consistent with autosomal recessive inheritance. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>In a family (family 12) with colonic adenomas, including 2 sibs with glioblastoma and cafe-au-lait spots, respectively, Hamilton et al. (1995) identified a truncating mutation in the PMS2 gene (600259.0001); a second PMS2 mutation (600249.0005) was later identified in this family by De Vos et al. (2004), indicating autosomal recessive inheritance. </p><p>In a girl who developed oligodendroglioma at age 14 years and colon carcinoma at age 18 years, De Rosa et al. (2000) identified compound heterozygosity for mutations in the PMS2 gene (600259.0002, 600259.0003). The girl's sister had died at age 14 of neuroblastoma. </p><p>In affected members of a consanguineous Guyanese family with variable expression of colorectal adenocarcinoma, acute leukemia, brain tumors, and cafe-au-lait spots, Trimbath et al. (2001) identified a homozygous mutation in the PMS2 gene (600259.0013). </p><p>In affected members of a consanguineous family in which 3 sibs had early onset of brain tumors, but no colonic lesions, De Vos et al. (2004) identified a homozygous nonsense mutation in the PMS2 gene (R802X; 600259.0004). In affected members of 5 of 6 consanguineous Pakistani families with MMRCS4, De Vos et al. (2006) identified homozygosity for the R802X mutation. There was evidence of a founder effect. Affected members of the remaining family studied by De Vos et al. (2006) carried a homozygous tyr181-to-ter mutation (Y181X) resulting from a 1-bp deletion. </p><p>In 2 sibs from a family (C01204) with MMRCS4, Auclair et al. (2007) identified compound heterozygosity for 2 mutations in the PMS2 gene (600259.0011, 600259.0012). </p><p>In a 12-year-old Turkish girl with colorectal adenocarcinoma and Ig class switch recombination (CSR) deficiency, Peron et al. (2008) identified homozygosity for a 4-exon deletion/18-bp insertion in the PMS2 gene (600259.0018). </p><p>In a boy (family 1) with MMRCS4, Kratz et al. (2009) identified a homozygous mutation in the PMS2 gene (C73X; 600259.0016). </p><p>Defects in the MMR genes are associated with microsatellite instability (MSI) in tumor DNA. One system classifies MSI into type A, defined by smaller allelic shifts, and type B, defined by comparatively larger allelic shifts. Using a 5-mononucleotide marker panel to analyze MSI, Giunti et al. (2009) found that only 2 of 34 pediatric glioma tumor samples had unstable markers consistent with MSI. Both of these tumors were glioblastoma multiforme, and both patients had a family history of the mismatch repair cancer syndrome. Genetic analysis identified compound heterozygous mutations in the PMS2 gene in 1 patient (121S) and a heterozygous mutation in the MLH1 gene in the other; a second MLH1 mutation was not identified in the second patient. Both tumors showed small size shifts in the alleles compared to the constitutional DNA, with differences in the range of 1 to 2 bp. A colorectal tumor from 1 patient's affected sister showed the larger type B MSI. Giunti et al. (2009) noted that colorectal cancers often have higher degrees of instability compared to gliomas, perhaps because of the higher cell turnover of intestinal cells compared to neurons. The findings suggested that the finding of type A MSI in pediatric gliomas may be an indicator of Turcot syndrome. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>In 13 patients from 7 unrelated Inuit families with an attenuated form of MMRCS, Li et al. (2015) identified a homozygous c.2002A-G transition in the PMS2 gene (600259.0019). Analysis of patient cells showed that the mutation resulted in a splicing defect and nonsense-mediated mRNA decay, although there were minor amounts of full-length transcripts and some residual normal full-length functional protein. Haplotype analysis indicated a founder effect estimated to have appeared late in the 11th century. The authors estimated an allele frequency of 1 in 16 individuals in the Inuit population of Nunavik in northern Quebec. The age at cancer onset in individuals homozygous for the c.2002A-G mutation was significantly later (median age 22 years) compared to individuals homozygous for truncating PMS2 mutations (8 years). There was also a difference in the tumor spectrum, with brain tumors being significantly less prevalent in c.2002A-G homozygotes (15%) compared to truncating homozygotes (67%). However, 1 patient homozygous for the c.2002A-G mutation developed a primitive neuroectodermal tumor at age 3 years. Li et al. (2015) concluded that even a low level of PMS2 expression likely delays cancer onset. </p>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Turcot et al. (1959)
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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De Vos, M., Hayward, B. E., Picton, S., Sheridan, E., Bonthron, D. T.
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<strong>Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.</strong>
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Gururangan, S., Frankel, W., Broaddus, R., Clendenning, M., Senter, L., McDonald, M., Eastwood, J., Reardon, D., Vredenburgh, J., Quinn, J., Friedman, H. S.
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<strong>Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation.</strong>
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Neuro Oncol. 10: 93-97, 2008.
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Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W.
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<strong>The molecular basis of Turcot's syndrome.</strong>
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Kratz, C. P., Holter, S., Etzler, J., Lauten, M., Pollett, A., Niemeyer, C. M., Gallinger, S., Wimmer, K.
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<strong>Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.</strong>
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Kratz, C. P., Niemeyer, C. M., Juttner, E., Kartal, M., Weninger, A., Schmitt-Graeff, A., Kontny, U., Lauten, M., Utzolino, S., Radecke, J., Fonatsch, C., Wimmer, K.
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<strong>Childhood T-cell non-Hodgkin's lymphoma, colorectal carcinoma and brain tumor in association with cafe-au-lait spots caused by a novel homozygous PMS2 mutation. (Letter)</strong>
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Leukemia 22: 1078-1080, 2008.
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Li, L., Hamel, N., Baker, K., McGuffin, M. J., Couillard, M., Gologan, A., Marcus, V. A., Chodirker, B., Chudley, A., Stefanovici, C., Durandy, A., Hegele, R. A., and 10 others.
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<strong>A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.</strong>
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<p class="mim-text-font">
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Peron, S., Metin, A., Gardes, P., Alyanakian, M.-A., Sheridan, E., Kratz, C. P., Fischer, A., Durandy, A.
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<strong>Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination.</strong>
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J. Exp. Med. 205: 2465-2472, 2008.
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[PubMed: 18824584]
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[Full Text: https://doi.org/10.1084/jem.20080789]
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Trimbath, J. D., Petersen, G. M., Erdman, S. H., Ferre, M., Luce, M. C., Giardiello, F. M.
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<strong>Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?</strong>
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Fam. Cancer 1: 101-105, 2001.
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[PubMed: 14574005]
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[Full Text: https://doi.org/10.1023/a:1013881832014]
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Turcot, J., Despres, J.-P., St. Pierre, F.
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<strong>Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases.</strong>
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Dis. Colon Rectum 2: 465-468, 1959.
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[PubMed: 13839882]
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[Full Text: https://doi.org/10.1007/BF02616938]
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