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<title>
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Entry
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- #614350 - LYNCH SYNDROME 5; LYNCH5
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- OMIM
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<span class="h4">#614350</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="/phenotypicSeries/PS120435"> <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="#diagnosis">Diagnosis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3245&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.diseaseinfosearch.org/x/8528" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=144" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0070272" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/614350" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA002160/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0070272" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 144<br />
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<strong>DO:</strong> 0070272<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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614350
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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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LYNCH SYNDROME 5; LYNCH5
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 5; HNPCC5
|
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</span>
|
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</h4>
|
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</div>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/245?start=-3&limit=10&highlight=245">
|
|
2p16.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Lynch syndrome 5
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614350"> 614350 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
MSH6
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600678"> 600678 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
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|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/614350" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS120435" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/614350" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/614350" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
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|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased risk of colorectal cancer <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229681&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229681</a>]</span><br /> -
|
|
Increased risk of endometrial cancer <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229680&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229680</a>]</span><br /> -
|
|
Increased risk of cancer <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553618&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553618</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Tumor cells show microsatellite instability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227405&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227405</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Incomplete penetrance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836598</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span><br /> -
|
|
Cancer onset usually in mid-adulthood<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the mutS homolog 6 gene (MSH6, <a href="/entry/600678#0001">600678.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Colorectal cancer, hereditary nonpolyposis
|
|
- <a href="/phenotypicSeries/PS120435">PS120435</a>
|
|
- 7 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/238?start=-3&limit=10&highlight=238"> 2p21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613244"> Lynch syndrome 8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613244"> 613244 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/185535"> EPCAM </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/185535"> 185535 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/239?start=-3&limit=10&highlight=239"> 2p21-p16.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120435"> Lynch syndrome 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120435"> 120435 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609309"> MSH2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609309"> 609309 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/245?start=-3&limit=10&highlight=245"> 2p16.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614350"> Lynch syndrome 5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614350"> 614350 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600678"> MSH6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600678"> 600678 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/135?start=-3&limit=10&highlight=135"> 3p24.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614331"> Colorectal cancer, hereditary nonpolyposis, type 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
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<p>A number sign (#) is used with this entry because Lynch syndrome-5 (LYNCH5), also known as hereditary nonpolyposis colorectal cancer type 5 (HNPCC5), is caused by heterozygous mutation in the MSH6 gene (<a href="/entry/600678">600678</a>) on chromosome 2p16.</p>
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<p>Lynch syndrome-5 (LYNCH5), or hereditary nonpolyposis colorectal cancer type 5 (HNPCC5), is a cancer predisposition syndrome characterized by onset of colorectal cancer and/or extracolonic cancers, particularly endometrial cancer, usually in mid-adulthood. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by <a href="#2" class="mim-tip-reference" title="Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others. <strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong> Clin. Genet. 87: 536-542, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25318681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25318681</a>] [<a href="https://doi.org/10.1111/cge.12526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25318681">Castellsague et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25318681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a general phenotypic description and a discussion of genetic heterogeneity of Lynch syndrome, see <a href="/entry/120435">120435</a>.</p>
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<p><a href="#4" class="mim-tip-reference" title="Miyaki, M., Konishi, M., Tanaka, K., Kikuchi-Yanoshita, R., Muraoka, M., Yasuno, M., Igari, T., Koike, M., Chiba, M., Mori, T. <strong>Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. (Letter)</strong> Nature Genet. 17: 271-272, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354786</a>] [<a href="https://doi.org/10.1038/ng1197-271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354786">Miyaki et al. (1997)</a> reported a family with HNPCC5. The proband had adult-onset colorectal carcinoma and endometrial carcinoma, and her sister had endometrial carcinoma. Other sisters who had had endometrial or ovarian carcinoma were assumed to have the same germline MSH6 mutation, as it was detected in their offspring. Although this family did not fulfill the Amsterdam criteria, patients in the family had colonic, endometrial, ovarian, and pancreatic carcinomas. <a href="#4" class="mim-tip-reference" title="Miyaki, M., Konishi, M., Tanaka, K., Kikuchi-Yanoshita, R., Muraoka, M., Yasuno, M., Igari, T., Koike, M., Chiba, M., Mori, T. <strong>Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. (Letter)</strong> Nature Genet. 17: 271-272, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354786</a>] [<a href="https://doi.org/10.1038/ng1197-271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354786">Miyaki et al. (1997)</a> considered it noteworthy that endometrial and ovarian carcinomas were predominant in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354786" 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="Wijnen, J., de Leeuw, W., Vasen, H., van der Klift, H., Moller, P., Stormorken, A., Meijers-Heijboer, H., Lindhout, D., Menko, F., Vossen, S., Moslein, G., Tops, C., Brocker-Vriends, A., Wu, Y., Hofstra, R., Sijmons, R., Cornelisse, C., Morreau, H., Fodde, R. <strong>Familial endometrial cancer in female carriers of MSH6 germline mutations. (Letter)</strong> Nature Genet. 23: 142-144, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508506</a>] [<a href="https://doi.org/10.1038/13773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508506">Wijnen et al. (1999)</a> found that atypical HNPCC families with MSH6 mutations displayed a very high frequency of atypical hyperplastic lesions and carcinomas of the endometrium: 73% in female MSH6 mutation carriers compared with 29% in MSH2 and 31% in MLH1 carriers. Moreover, delayed age of cancer onset and incomplete penetrance were characteristic clinical features of the MSH6 mutation carriers. The results indicated that tumors of the endometrium (<a href="/entry/608089">608089</a>) represent the most common clinical manifestation of HNPCC among female MSH6 mutation carriers and that colorectal cancer cannot be considered an obligatory requisite to define HNPCC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508506" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Wagner, A., Hendriks, Y., Meijers-Heijboer, E. J., de Leeuw, W. J. F., Morreau, H., Hofstra, R., Tops, C., Bik, E., Brocker-Vriends, A. H. J. T., van der Meer, C., Lindhout, D., Vasen, H. F. A., Breuning, M. H., Cornelisse, C. J., van Krimpen, C., Niermeijer, M. F., Zwinderman, A. H., Wijnen, J., Fodde, R. <strong>Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.</strong> J. Med. Genet. 38: 318-322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11333868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11333868</a>] [<a href="https://doi.org/10.1136/jmg.38.5.318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11333868">Wagner et al. (2001)</a> found that colorectal cancer was significantly decreased in a large Dutch family with atypical HNPCC and an MSH6 mutation compared to families with mutations in MSH2 (<a href="/entry/609309">609309</a>) or MLH1 (<a href="/entry/120436">120436</a>) (p less than 0.001). Endometrial cancer was frequent among female mutation carriers (6 of 13 malignant tumors), and transitional cell carcinoma of the urinary tract was present in 10% of male and female carriers. The mean age of onset of colorectal and endometrial cancer was delayed compared to that in families with MSH2 or MLH1 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11333868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Suchy, J., Kurzawski, G., Jakubowska, A., Lubinski, J. <strong>Ovarian cancer of endometrioid type as part of the MSH6 gene mutation phenotype.</strong> J. Hum. Genet. 47: 529-531, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376742</a>] [<a href="https://doi.org/10.1007/s100380200079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12376742">Suchy et al. (2002)</a> described a Polish MSH6 family in which a late-onset endometrial type of ovarian cancer was a feature. In the proband, bilateral ovarian cancer was discovered at the age of 49 years. The father died of colon cancer at the age of 83 years and her paternal grandmother died of endometrial cancer at the age of 69 years. Endometrial cancer was diagnosed at the age of 57 years in a cousin. Ovarian cancer had been reported in an MSH6 family by <a href="#8" class="mim-tip-reference" title="Wagner, A., Hendriks, Y., Meijers-Heijboer, E. J., de Leeuw, W. J. F., Morreau, H., Hofstra, R., Tops, C., Bik, E., Brocker-Vriends, A. H. J. T., van der Meer, C., Lindhout, D., Vasen, H. F. A., Breuning, M. H., Cornelisse, C. J., van Krimpen, C., Niermeijer, M. F., Zwinderman, A. H., Wijnen, J., Fodde, R. <strong>Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.</strong> J. Med. Genet. 38: 318-322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11333868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11333868</a>] [<a href="https://doi.org/10.1136/jmg.38.5.318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11333868">Wagner et al. (2001)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11333868+12376742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a retrospective U.S. population-based study, <a href="#3" class="mim-tip-reference" title="Kastrinos, F., Mukherjee, B., Tayob, N., Wang, F., Sparr, J., Raymond, V. M., Bandipalliam, P., Stoffel, E. M., Gruber, S. B., Syngal, S. <strong>Risk of pancreatic cancer in families with Lynch syndrome.</strong> JAMA 302: 1790-1795, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19861671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19861671</a>] [<a href="https://doi.org/10.1001/jama.2009.1529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19861671">Kastrinos et al. (2009)</a> found 3 cases of pancreatic cancer among 11 families with MSH6 mutations. Although the numbers were too small to calculate a risk estimate, the authors concluded that pancreatic cancer is a component of HNPCC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19861671" 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="Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others. <strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong> Clin. Genet. 87: 536-542, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25318681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25318681</a>] [<a href="https://doi.org/10.1111/cge.12526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25318681">Castellsague et al. (2015)</a> reported 11 families of French Canadian descent from Quebec with HNPCC5. The average age at diagnosis was 44.2 years, and tumors fell within the HNPCC spectrum, but included mainly colorectal and endometrial cancer. Other rare tumors included breast cancer, cervical cancer, ovarian cancer, stomach cancer, and non-Hodgkin lymphoma. Among all families, 8 (73%) of 11 affected carrier females had endometrial cancer, suggesting that this is a typical presenting MSH6-related cancer in women. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25318681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Wijnen, J., de Leeuw, W., Vasen, H., van der Klift, H., Moller, P., Stormorken, A., Meijers-Heijboer, H., Lindhout, D., Menko, F., Vossen, S., Moslein, G., Tops, C., Brocker-Vriends, A., Wu, Y., Hofstra, R., Sijmons, R., Cornelisse, C., Morreau, H., Fodde, R. <strong>Familial endometrial cancer in female carriers of MSH6 germline mutations. (Letter)</strong> Nature Genet. 23: 142-144, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508506</a>] [<a href="https://doi.org/10.1038/13773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508506">Wijnen et al. (1999)</a> found that 7 of 10 germline mutations in MSH6 had been identified in atypical HNPCC families not fulfilling the Amsterdam criteria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508506" 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>Among 33 cancer families with proven mutations in the MSH6 gene, <a href="#6" class="mim-tip-reference" title="Sjursen, W., Haukanes, B. I., Grindedal, E. M., Aarset, H., Stormorken, A., Engebretsen, L. F., Jonsrud, C., Bjornevoll, I., Andresen, P. A., Ariansen, S., Lavik, L. A. S., Gilde, B., Bowitz-Lothe, I. M., Maehle, L., Moller, P. <strong>Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers.</strong> J. Med. Genet. 47: 579-585, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20587412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20587412</a>] [<a href="https://doi.org/10.1136/jmg.2010.077677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20587412">Sjursen et al. (2010)</a> found that the sensitivity for diagnostic criteria using the original Amsterdam guidelines, the revised Amsterdam guidelines, and the Bethesda II guidelines were inadequate for detecting potential MSH6 mutation carriers. The sensitivities using these guidelines were less than 50%. <a href="#6" class="mim-tip-reference" title="Sjursen, W., Haukanes, B. I., Grindedal, E. M., Aarset, H., Stormorken, A., Engebretsen, L. F., Jonsrud, C., Bjornevoll, I., Andresen, P. A., Ariansen, S., Lavik, L. A. S., Gilde, B., Bowitz-Lothe, I. M., Maehle, L., Moller, P. <strong>Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers.</strong> J. Med. Genet. 47: 579-585, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20587412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20587412</a>] [<a href="https://doi.org/10.1136/jmg.2010.077677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20587412">Sjursen et al. (2010)</a> suggested that MSH6 mutations may be more common than currently assumed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20587412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Buttin, B. M., Powell, M. A., Mutch, D. G., Babb, S. A., Huettner, P. C., Edmonston, T. B., Herzog, T. J., Rader, J. S., Gibb, R. K., Whelan, A. J., Goodfellow, P. J. <strong>Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history.</strong> Am. J. Hum. Genet. 74: 1262-1269, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15098177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15098177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15098177[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/10.1086/421332" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15098177">Buttin et al. (2004)</a> studied the penetrance and expressivity of MSH6 mutations in kindreds ascertained through endometrial cancer probands unselected for family history. MSH6 mutation status was determined for 59 family members. Of these 59 individuals, 19 (32%) had confirmed cancers or precancers. There was an excess of mutation carriers among the 19 affected family members (11/19, 58%) compared with those among the 40 unaffecteds (8/40, 20%), giving an odds ratio of 5.5. Overall estimated penetrance of the MSH6 mutations was 57.7%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15098177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The transmission pattern of HNPCC5 in the families reported by <a href="#2" class="mim-tip-reference" title="Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others. <strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong> Clin. Genet. 87: 536-542, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25318681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25318681</a>] [<a href="https://doi.org/10.1111/cge.12526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25318681">Castellsague et al. (2015)</a> was consistent with autosomal dominant inheritance and incomplete penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25318681" 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 the HCT-15 colorectal cancer cell line, <a href="#5" class="mim-tip-reference" title="Papadopoulos, N., Nicolaides, N. C., Liu, B., Parsons, R., Lengauer, C., Palombo, F., D'Arrigo, A., Markowitz, S., Willson, J. K. V., Kinzler, K. W., Jiricny, J., Vogelstein, B. <strong>Mutations of GTBP in genetically unstable cells.</strong> Science 268: 1915-1917, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604266</a>] [<a href="https://doi.org/10.1126/science.7604266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7604266">Papadopoulos et al. (1995)</a> identified a truncating mutation in the MSH6 gene (<a href="/entry/600678#0001">600678.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7604266" 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 an HNPCC5 family, <a href="#4" class="mim-tip-reference" title="Miyaki, M., Konishi, M., Tanaka, K., Kikuchi-Yanoshita, R., Muraoka, M., Yasuno, M., Igari, T., Koike, M., Chiba, M., Mori, T. <strong>Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. (Letter)</strong> Nature Genet. 17: 271-272, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354786</a>] [<a href="https://doi.org/10.1038/ng1197-271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354786">Miyaki et al. (1997)</a> identified a heterozygous germline truncating mutation in the MSH6 gene (<a href="/entry/600678#0004">600678.0004</a>). In addition to the germline mutation, somatic mutations of MSH6 were detected in colorectal and endometrial carcinomas from the proband in this family. These somatic mutations were presumably in the alleles without the germline mutation, suggesting that inactivation of both alleles of MSH6 was the cause of the phenotype and the stimulus for neoplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354786" 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 11 probands of French Canadian descent in the Province of Quebec with HNPCC5, <a href="#2" class="mim-tip-reference" title="Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others. <strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong> Clin. Genet. 87: 536-542, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25318681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25318681</a>] [<a href="https://doi.org/10.1111/cge.12526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25318681">Castellsague et al. (2015)</a> identified a heterozygous nonsense mutation in the MSH6 gene (Q4X; <a href="/entry/600678#0018">600678.0018</a>). Analysis of 27 additional family members indicated that the mutation cosegregated with cancer in 15 of 23 carriers, consistent with incomplete penetrance. Heterozygous carriers had an average age of cancer diagnosis at 44.2 years; 1 homozygous carrier had onset at age 10 years. All evaluable tumors showed loss of MSH6 protein and microsatellite instability (MSI); no loss of heterozygosity (LOH) was identified in any of the evaluated tumors, but the authors suggested that the gene was likely inactivated by point mutations or deletions. Analysis of this mutation among a larger population-based cohort of French Canadians showed that only 1 of 187 patients with colorectal cancer had the mutation, whereas 7 of 381 patients with endometrial cancer carried the mutation, yielding an odds ratio (OR) of 7.5 (p less than 0.0001). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25318681" 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 the French Canadian population in Quebec, <a href="#2" class="mim-tip-reference" title="Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others. <strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong> Clin. Genet. 87: 536-542, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25318681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25318681</a>] [<a href="https://doi.org/10.1111/cge.12526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25318681">Castellsague et al. (2015)</a> found evidence of a founder effect of the Q4X MSH6 mutation (<a href="/entry/600678#0018">600678.0018</a>). Haplotype analysis estimated that the mutation occurred about 513 years ago. The carrier rate in this population was estimated at about 1 in 400. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25318681" 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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Buttin, B. M., Powell, M. A., Mutch, D. G., Babb, S. A., Huettner, P. C., Edmonston, T. B., Herzog, T. J., Rader, J. S., Gibb, R. K., Whelan, A. J., Goodfellow, P. J.
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<strong>Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history.</strong>
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Am. J. Hum. Genet. 74: 1262-1269, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15098177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15098177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15098177[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=15098177" 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/10.1086/421332" target="_blank">Full Text</a>]
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Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others.
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<strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong>
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Clin. Genet. 87: 536-542, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25318681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25318681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25318681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.12526" target="_blank">Full Text</a>]
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Kastrinos, F., Mukherjee, B., Tayob, N., Wang, F., Sparr, J., Raymond, V. M., Bandipalliam, P., Stoffel, E. M., Gruber, S. B., Syngal, S.
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<strong>Risk of pancreatic cancer in families with Lynch syndrome.</strong>
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JAMA 302: 1790-1795, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19861671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19861671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19861671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/jama.2009.1529" target="_blank">Full Text</a>]
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Miyaki, M., Konishi, M., Tanaka, K., Kikuchi-Yanoshita, R., Muraoka, M., Yasuno, M., Igari, T., Koike, M., Chiba, M., Mori, T.
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<strong>Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. (Letter)</strong>
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Nature Genet. 17: 271-272, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354786</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354786" 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/ng1197-271" target="_blank">Full Text</a>]
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Papadopoulos, N., Nicolaides, N. C., Liu, B., Parsons, R., Lengauer, C., Palombo, F., D'Arrigo, A., Markowitz, S., Willson, J. K. V., Kinzler, K. W., Jiricny, J., Vogelstein, B.
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<strong>Mutations of GTBP in genetically unstable cells.</strong>
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Science 268: 1915-1917, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604266</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7604266" 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/10.1126/science.7604266" target="_blank">Full Text</a>]
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</p>
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<a id="6" class="mim-anchor"></a>
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<a id="Sjursen2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sjursen, W., Haukanes, B. I., Grindedal, E. M., Aarset, H., Stormorken, A., Engebretsen, L. F., Jonsrud, C., Bjornevoll, I., Andresen, P. A., Ariansen, S., Lavik, L. A. S., Gilde, B., Bowitz-Lothe, I. M., Maehle, L., Moller, P.
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<strong>Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers.</strong>
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J. Med. Genet. 47: 579-585, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20587412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20587412</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20587412" 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.2010.077677" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Suchy2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Suchy, J., Kurzawski, G., Jakubowska, A., Lubinski, J.
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<strong>Ovarian cancer of endometrioid type as part of the MSH6 gene mutation phenotype.</strong>
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J. Hum. Genet. 47: 529-531, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376742" 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/s100380200079" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Wagner2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wagner, A., Hendriks, Y., Meijers-Heijboer, E. J., de Leeuw, W. J. F., Morreau, H., Hofstra, R., Tops, C., Bik, E., Brocker-Vriends, A. H. J. T., van der Meer, C., Lindhout, D., Vasen, H. F. A., Breuning, M. H., Cornelisse, C. J., van Krimpen, C., Niermeijer, M. F., Zwinderman, A. H., Wijnen, J., Fodde, R.
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<strong>Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.</strong>
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J. Med. Genet. 38: 318-322, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11333868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11333868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11333868" 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.38.5.318" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Wijnen1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wijnen, J., de Leeuw, W., Vasen, H., van der Klift, H., Moller, P., Stormorken, A., Meijers-Heijboer, H., Lindhout, D., Menko, F., Vossen, S., Moslein, G., Tops, C., Brocker-Vriends, A., Wu, Y., Hofstra, R., Sijmons, R., Cornelisse, C., Morreau, H., Fodde, R.
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<strong>Familial endometrial cancer in female carriers of MSH6 germline mutations. (Letter)</strong>
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Nature Genet. 23: 142-144, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508506</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508506" 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/10.1038/13773" target="_blank">Full Text</a>]
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 12/7/2015
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf : 11/21/2011
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 11/16/2022
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carol : 11/15/2022<br>carol : 06/21/2016<br>alopez : 12/15/2015<br>ckniffin : 12/7/2015<br>alopez : 11/21/2011
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<span class="mim-font">
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<strong>#</strong> 614350
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LYNCH SYNDROME 5; LYNCH5
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 5; HNPCC5
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<strong>ORPHA:</strong> 144;
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<strong>DO:</strong> 0070272;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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2p16.3
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<span class="mim-font">
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Lynch syndrome 5
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<span class="mim-font">
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614350
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<span class="mim-font">
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Autosomal dominant
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<td>
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<span class="mim-font">
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3
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MSH6
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<span class="mim-font">
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600678
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Lynch syndrome-5 (LYNCH5), also known as hereditary nonpolyposis colorectal cancer type 5 (HNPCC5), is caused by heterozygous mutation in the MSH6 gene (600678) on chromosome 2p16.</p>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Lynch syndrome-5 (LYNCH5), or hereditary nonpolyposis colorectal cancer type 5 (HNPCC5), is a cancer predisposition syndrome characterized by onset of colorectal cancer and/or extracolonic cancers, particularly endometrial cancer, usually in mid-adulthood. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Castellsague et al., 2015). </p><p>For a general phenotypic description and a discussion of genetic heterogeneity of Lynch syndrome, see 120435.</p>
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<h4>
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<strong>Clinical Features</strong>
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<p>Miyaki et al. (1997) reported a family with HNPCC5. The proband had adult-onset colorectal carcinoma and endometrial carcinoma, and her sister had endometrial carcinoma. Other sisters who had had endometrial or ovarian carcinoma were assumed to have the same germline MSH6 mutation, as it was detected in their offspring. Although this family did not fulfill the Amsterdam criteria, patients in the family had colonic, endometrial, ovarian, and pancreatic carcinomas. Miyaki et al. (1997) considered it noteworthy that endometrial and ovarian carcinomas were predominant in this family. </p><p>Wijnen et al. (1999) found that atypical HNPCC families with MSH6 mutations displayed a very high frequency of atypical hyperplastic lesions and carcinomas of the endometrium: 73% in female MSH6 mutation carriers compared with 29% in MSH2 and 31% in MLH1 carriers. Moreover, delayed age of cancer onset and incomplete penetrance were characteristic clinical features of the MSH6 mutation carriers. The results indicated that tumors of the endometrium (608089) represent the most common clinical manifestation of HNPCC among female MSH6 mutation carriers and that colorectal cancer cannot be considered an obligatory requisite to define HNPCC. </p><p>Wagner et al. (2001) found that colorectal cancer was significantly decreased in a large Dutch family with atypical HNPCC and an MSH6 mutation compared to families with mutations in MSH2 (609309) or MLH1 (120436) (p less than 0.001). Endometrial cancer was frequent among female mutation carriers (6 of 13 malignant tumors), and transitional cell carcinoma of the urinary tract was present in 10% of male and female carriers. The mean age of onset of colorectal and endometrial cancer was delayed compared to that in families with MSH2 or MLH1 mutations. </p><p>Suchy et al. (2002) described a Polish MSH6 family in which a late-onset endometrial type of ovarian cancer was a feature. In the proband, bilateral ovarian cancer was discovered at the age of 49 years. The father died of colon cancer at the age of 83 years and her paternal grandmother died of endometrial cancer at the age of 69 years. Endometrial cancer was diagnosed at the age of 57 years in a cousin. Ovarian cancer had been reported in an MSH6 family by Wagner et al. (2001). </p><p>In a retrospective U.S. population-based study, Kastrinos et al. (2009) found 3 cases of pancreatic cancer among 11 families with MSH6 mutations. Although the numbers were too small to calculate a risk estimate, the authors concluded that pancreatic cancer is a component of HNPCC. </p><p>Castellsague et al. (2015) reported 11 families of French Canadian descent from Quebec with HNPCC5. The average age at diagnosis was 44.2 years, and tumors fell within the HNPCC spectrum, but included mainly colorectal and endometrial cancer. Other rare tumors included breast cancer, cervical cancer, ovarian cancer, stomach cancer, and non-Hodgkin lymphoma. Among all families, 8 (73%) of 11 affected carrier females had endometrial cancer, suggesting that this is a typical presenting MSH6-related cancer in women. </p>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wijnen et al. (1999) found that 7 of 10 germline mutations in MSH6 had been identified in atypical HNPCC families not fulfilling the Amsterdam criteria. </p><p>Among 33 cancer families with proven mutations in the MSH6 gene, Sjursen et al. (2010) found that the sensitivity for diagnostic criteria using the original Amsterdam guidelines, the revised Amsterdam guidelines, and the Bethesda II guidelines were inadequate for detecting potential MSH6 mutation carriers. The sensitivities using these guidelines were less than 50%. Sjursen et al. (2010) suggested that MSH6 mutations may be more common than currently assumed. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Buttin et al. (2004) studied the penetrance and expressivity of MSH6 mutations in kindreds ascertained through endometrial cancer probands unselected for family history. MSH6 mutation status was determined for 59 family members. Of these 59 individuals, 19 (32%) had confirmed cancers or precancers. There was an excess of mutation carriers among the 19 affected family members (11/19, 58%) compared with those among the 40 unaffecteds (8/40, 20%), giving an odds ratio of 5.5. Overall estimated penetrance of the MSH6 mutations was 57.7%. </p><p>The transmission pattern of HNPCC5 in the families reported by Castellsague et al. (2015) was consistent with autosomal dominant inheritance and incomplete penetrance. </p>
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</span>
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<br />
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>In the HCT-15 colorectal cancer cell line, Papadopoulos et al. (1995) identified a truncating mutation in the MSH6 gene (600678.0001). </p><p>In an HNPCC5 family, Miyaki et al. (1997) identified a heterozygous germline truncating mutation in the MSH6 gene (600678.0004). In addition to the germline mutation, somatic mutations of MSH6 were detected in colorectal and endometrial carcinomas from the proband in this family. These somatic mutations were presumably in the alleles without the germline mutation, suggesting that inactivation of both alleles of MSH6 was the cause of the phenotype and the stimulus for neoplasia. </p><p>In 11 probands of French Canadian descent in the Province of Quebec with HNPCC5, Castellsague et al. (2015) identified a heterozygous nonsense mutation in the MSH6 gene (Q4X; 600678.0018). Analysis of 27 additional family members indicated that the mutation cosegregated with cancer in 15 of 23 carriers, consistent with incomplete penetrance. Heterozygous carriers had an average age of cancer diagnosis at 44.2 years; 1 homozygous carrier had onset at age 10 years. All evaluable tumors showed loss of MSH6 protein and microsatellite instability (MSI); no loss of heterozygosity (LOH) was identified in any of the evaluated tumors, but the authors suggested that the gene was likely inactivated by point mutations or deletions. Analysis of this mutation among a larger population-based cohort of French Canadians showed that only 1 of 187 patients with colorectal cancer had the mutation, whereas 7 of 381 patients with endometrial cancer carried the mutation, yielding an odds ratio (OR) of 7.5 (p less than 0.0001). </p>
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<strong>Population Genetics</strong>
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<p>In the French Canadian population in Quebec, Castellsague et al. (2015) found evidence of a founder effect of the Q4X MSH6 mutation (600678.0018). Haplotype analysis estimated that the mutation occurred about 513 years ago. The carrier rate in this population was estimated at about 1 in 400. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</h4>
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Buttin, B. M., Powell, M. A., Mutch, D. G., Babb, S. A., Huettner, P. C., Edmonston, T. B., Herzog, T. J., Rader, J. S., Gibb, R. K., Whelan, A. J., Goodfellow, P. J.
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<strong>Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history.</strong>
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Am. J. Hum. Genet. 74: 1262-1269, 2004.
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[PubMed: 15098177]
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[Full Text: https://doi.org/10.1086/421332]
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Castellsague, E., Liu, J., Volenik, A., Giroux, S., Gagne, R., Maranda, B., Roussel-Jobin, A., Latreille, J., Laframboise, R., Palma, L., Kasprzak, L., Marcus, V. A., and 14 others.
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<strong>Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.</strong>
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Clin. Genet. 87: 536-542, 2015.
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[PubMed: 25318681]
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[Full Text: https://doi.org/10.1111/cge.12526]
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Kastrinos, F., Mukherjee, B., Tayob, N., Wang, F., Sparr, J., Raymond, V. M., Bandipalliam, P., Stoffel, E. M., Gruber, S. B., Syngal, S.
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<strong>Risk of pancreatic cancer in families with Lynch syndrome.</strong>
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JAMA 302: 1790-1795, 2009.
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[PubMed: 19861671]
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[Full Text: https://doi.org/10.1001/jama.2009.1529]
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<li>
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<p class="mim-text-font">
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Miyaki, M., Konishi, M., Tanaka, K., Kikuchi-Yanoshita, R., Muraoka, M., Yasuno, M., Igari, T., Koike, M., Chiba, M., Mori, T.
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<strong>Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. (Letter)</strong>
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Nature Genet. 17: 271-272, 1997.
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[PubMed: 9354786]
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[Full Text: https://doi.org/10.1038/ng1197-271]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Papadopoulos, N., Nicolaides, N. C., Liu, B., Parsons, R., Lengauer, C., Palombo, F., D'Arrigo, A., Markowitz, S., Willson, J. K. V., Kinzler, K. W., Jiricny, J., Vogelstein, B.
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<strong>Mutations of GTBP in genetically unstable cells.</strong>
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Science 268: 1915-1917, 1995.
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[PubMed: 7604266]
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[Full Text: https://doi.org/10.1126/science.7604266]
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</p>
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Sjursen, W., Haukanes, B. I., Grindedal, E. M., Aarset, H., Stormorken, A., Engebretsen, L. F., Jonsrud, C., Bjornevoll, I., Andresen, P. A., Ariansen, S., Lavik, L. A. S., Gilde, B., Bowitz-Lothe, I. M., Maehle, L., Moller, P.
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<strong>Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers.</strong>
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J. Med. Genet. 47: 579-585, 2010.
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[PubMed: 20587412]
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[Full Text: https://doi.org/10.1136/jmg.2010.077677]
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Suchy, J., Kurzawski, G., Jakubowska, A., Lubinski, J.
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<strong>Ovarian cancer of endometrioid type as part of the MSH6 gene mutation phenotype.</strong>
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J. Hum. Genet. 47: 529-531, 2002.
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[PubMed: 12376742]
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[Full Text: https://doi.org/10.1007/s100380200079]
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Wagner, A., Hendriks, Y., Meijers-Heijboer, E. J., de Leeuw, W. J. F., Morreau, H., Hofstra, R., Tops, C., Bik, E., Brocker-Vriends, A. H. J. T., van der Meer, C., Lindhout, D., Vasen, H. F. A., Breuning, M. H., Cornelisse, C. J., van Krimpen, C., Niermeijer, M. F., Zwinderman, A. H., Wijnen, J., Fodde, R.
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<strong>Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.</strong>
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J. Med. Genet. 38: 318-322, 2001.
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[PubMed: 11333868]
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[Full Text: https://doi.org/10.1136/jmg.38.5.318]
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<p class="mim-text-font">
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Wijnen, J., de Leeuw, W., Vasen, H., van der Klift, H., Moller, P., Stormorken, A., Meijers-Heijboer, H., Lindhout, D., Menko, F., Vossen, S., Moslein, G., Tops, C., Brocker-Vriends, A., Wu, Y., Hofstra, R., Sijmons, R., Cornelisse, C., Morreau, H., Fodde, R.
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<strong>Familial endometrial cancer in female carriers of MSH6 germline mutations. (Letter)</strong>
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Nature Genet. 23: 142-144, 1999.
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[PubMed: 10508506]
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[Full Text: https://doi.org/10.1038/13773]
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Cassandra L. Kniffin - updated : 12/7/2015
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Anne M. Stumpf : 11/21/2011
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carol : 11/16/2022<br>carol : 11/15/2022<br>carol : 06/21/2016<br>alopez : 12/15/2015<br>ckniffin : 12/7/2015<br>alopez : 11/21/2011
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