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<title>
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Entry
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- #614337 - LYNCH SYNDROME 4; LYNCH4
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- OMIM
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<span class="h4">#614337</span>
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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="#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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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(LYNCH 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=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/8527" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=614337[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=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 style="display: table-cell;">Animal Models</div>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0070275" 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/614337" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0070275" 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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</span>
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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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<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> 0070275<br />
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">ICD+</a>
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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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614337
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</span>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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LYNCH SYNDROME 4; LYNCH4
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</h3>
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</div>
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<div>
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<br />
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
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COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 4; HNPCC4
|
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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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<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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<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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Lynch 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/614337"> 614337 </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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</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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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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<div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS120435" 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/614337" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/614337" 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="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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Colorectal cancer, hereditary nonpolyposis
|
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- <a href="/phenotypicSeries/PS120435">PS120435</a>
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- 7 Entries
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</h5>
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
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<thead>
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<tr>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Location</strong>
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</th>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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<strong>Phenotype</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Inheritance</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />mapping key</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />MIM number</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Gene/Locus</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Gene/Locus<br />MIM number</strong>
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
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<tr>
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<td>
|
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<span class="mim-font">
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<a href="/geneMap/2/238?start=-3&limit=10&highlight=238"> 2p21 </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/613244"> Lynch syndrome 8 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
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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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|
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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/613244"> 613244 </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/185535"> EPCAM </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/185535"> 185535 </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/2/239?start=-3&limit=10&highlight=239"> 2p21-p16.3 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120435"> Lynch syndrome 1 </a>
|
|
</span>
|
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</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>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
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<a href="/entry/609309"> MSH2 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609309"> 609309 </a>
|
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</span>
|
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</td>
|
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</tr>
|
|
|
|
<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>
|
|
|
|
</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>
|
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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>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600678"> 600678 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
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<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>
|
|
<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/614331"> 614331 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/190182"> TGFBR2 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/190182"> 190182 </a>
|
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</span>
|
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</td>
|
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</tr>
|
|
|
|
<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>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
<a href="/entry/609310"> Lynch syndrome 2 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
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<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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|
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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/609310"> 609310 </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/120436"> MLH1 </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/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>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614337"> Lynch syndrome 4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
|
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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>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614337"> 614337 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
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<a href="/entry/600259"> PMS2 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600259"> 600259 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
|
|
<tr>
|
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<td>
|
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<span class="mim-font">
|
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|
|
<a href="/geneMap/14/395?start=-3&limit=10&highlight=395"> 14q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614385"> Colorectal cancer, hereditary nonpolyposis, type 7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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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>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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<a href="/entry/614385"> 614385 </a>
|
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</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
<a href="/entry/604395"> MLH3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604395"> 604395 </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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|
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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 Lynch syndrome-4 (LYNCH4), also known as hereditary nonpolyposis colorectal cancer type 4 (HNPCC4), is caused by heterozygous mutation in the PMS2 gene (<a href="/entry/600259">600259</a>) on chromosome 7p22.</p><p>For a discussion of genetic heterogeneity of Lynch syndrome, see <a href="/entry/120435">120435</a>.</p>
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</span>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Lynch syndrome-4 (LYNCH4), or hereditary nonpolyposis colorectal cancer type 4 (HNPCC4), is an autosomal dominant disorder characterized primarily by the development of early-onset colorectal cancer. It is associated with the development of a variety of epithelial tumors that include endometrial cancer, stomach cancer, and ovarian cancer (summary by <a href="#6" class="mim-tip-reference" title="Thompson, E., Meldrum, C. J., Crooks, R., McPhillips, M., Thomas, L., Spigelman, A. D., Scott, R. J. <strong>Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.</strong> Clin. Genet. 65: 215-225, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14756672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14756672</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00214.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14756672">Thompson et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14756672" 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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</span>
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<p><a href="#4" class="mim-tip-reference" title="Nicolaides, N. C., Papadopoulos, N., Liu, B., Wei, Y.-F., Carter, K. C., Ruben, S. M., Rosen, C. A., Haseltine, W. A., Fleischmann, R. D., Fraser, C. M., Adams, M. D., Venter, J. C., Dunlop, M. G., Hamilton, S. R., Petersen, G. M., de la Chapelle, A., Vogelstein, B., Kinzler, K. W. <strong>Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.</strong> Nature 371: 75-80, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8072530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8072530</a>] [<a href="https://doi.org/10.1038/371075a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8072530">Nicolaides et al. (1994)</a> identified a germline deletion in the PMS2 gene in a patient with a family history of HNPCC. A second deletion was found in the patient's tumor sample. The tumor from this patient exhibited microsatellite instability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8072530" 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>To examine the contribution of the PMS2 and EXO1 (<a href="/entry/606063">606063</a>) genes to the HNPCC disease phenotype, <a href="#6" class="mim-tip-reference" title="Thompson, E., Meldrum, C. J., Crooks, R., McPhillips, M., Thomas, L., Spigelman, A. D., Scott, R. J. <strong>Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.</strong> Clin. Genet. 65: 215-225, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14756672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14756672</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00214.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14756672">Thompson et al. (2004)</a> studied 21 families negative for mutations in MSH2 (<a href="/entry/609309">609309</a>) and MLH1 (<a href="/entry/120436">120436</a>) that fulfilled the Amsterdam diagnostic criteria. They found that mutation in PMS2 accounts for only a small proportion of HNPCC families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14756672" 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="Worthley, D. L., Walsh, M. D., Barker, M., Ruszkiewicz, A., Bennett, G., Phillips, K., Suthers, G. <strong>Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer.</strong> Gastroenterology 128: 1431-1436, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887124</a>] [<a href="https://doi.org/10.1053/j.gastro.2005.04.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15887124">Worthley et al. (2005)</a> tested a cohort of 80 patients with features suggestive of HNPCC for evidence of defective mismatch repair and exclusive loss of expression of the PMS2 gene in the tumor. They identified a family with HNPCC due to autosomal dominant inheritance of a loss-of-function mutation in the PMS2 gene and stated that this was the first description of such a kindred. The proband had been diagnosed with cancer of the transverse colon at 49 years of age. Two years later he developed and subsequently died of metastatic esophageal adenocarcinoma. His mother developed endometrial cancer at 60 years of age and carcinoma of the cecum at age 80 years. His maternal grandfather and great-uncle developed colorectal cancer at 66 and 45 years of age, respectively. The brother of the proband had 2 sessile polyps removed from the sigmoid colon, 1 at age 47 and the other at age 49. A maternal uncle died of metastatic squamous cell carcinoma of the esophagus, and his daughter developed breast cancer at the age of 25 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887124" 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="Hendriks, Y. M. C., Jagmohan-Changur, S., Van der Klift, H. M., Morreau, H., Van Puijenbroek, M., Tops, C., Van Os, T., Wagner, A., Ausems, M. G. F. M., Gomez, E., Breuning, M. J., Brocker-Vriends, A. H. J. T., Vasen, H. F. A., Wijnen, J. T. <strong>Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).</strong> Gastroenterology 130: 312-322, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16472587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16472587</a>] [<a href="https://doi.org/10.1053/j.gastro.2005.10.052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16472587">Hendriks et al. (2006)</a> summarized the phenotype of 7 families with colorectal cancer and a truncating mutation in the PMS2 gene. Although only 3 of the 7 families fulfilled the Amsterdam criteria, in 6 of the 7 families, the pattern of inheritance appeared to be autosomal dominant. The most frequently observed cancer in proven mutation carriers was colorectal carcinoma, followed by endometrial carcinoma and ovarian carcinoma. The mean age at diagnosis was 52 years, approximately 7 to 8 years higher than the mean age of diagnosis observed in families associated with MLH1 and MSH2 mutations. <a href="#3" class="mim-tip-reference" title="Hendriks, Y. M. C., Jagmohan-Changur, S., Van der Klift, H. M., Morreau, H., Van Puijenbroek, M., Tops, C., Van Os, T., Wagner, A., Ausems, M. G. F. M., Gomez, E., Breuning, M. J., Brocker-Vriends, A. H. J. T., Vasen, H. F. A., Wijnen, J. T. <strong>Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).</strong> Gastroenterology 130: 312-322, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16472587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16472587</a>] [<a href="https://doi.org/10.1053/j.gastro.2005.10.052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16472587">Hendriks et al. (2006)</a> hypothesized that the attenuated phenotype of families with PMS2 mutations may be explained by the fact that in the absence of PMS2, a functional MLH1 and MLH3 (<a href="/entry/604395">604395</a>) heterodimeric protein can be formed that is able to repair DNA mismatches. In families with MLH1 or MSH2 gene defects, no alternative heterodimers can be created, with consequently a complete inactivation of the mismatch repair system with massive microsatellite instability and a higher risk of cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16472587" 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="Goodenberger, M. L., Thomas, B. C., Riegert-Johnson, D., Boland, C. R., Plon, S. E., Clendenning, M., Win, A. K., Senter, L., Lipkin, S. M., Stadler, Z. K., Macrae, F. A., Lynch, H. T., and 18 others. <strong>PMS2 monoallelic mutation carriers: the known unknown.</strong> Genet. Med. 18: 13-19, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25856668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25856668</a>] [<a href="https://doi.org/10.1038/gim.2015.27" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25856668">Goodenberger et al. (2016)</a> examined the penetrance and presentation of colorectal cancer in 234 monoallelic PMS2 mutation carriers from 170 families. Approximately 8% of those with colorectal cancer were diagnosed before age 30, and each of these tumors presented on the left side of the colon. As it was unknown what causes the early onset of colorectal cancer in some families with monoallelic PMS2 germline mutations, the authors recommended against reducing cancer surveillance guidelines in families found to have monoallelic PMS2 mutations, in spite of the reduced penetrance (15-20%, according to <a href="#5" class="mim-tip-reference" title="Senter, L., Clendenning, M., Sotamaa, K., Hampel, H., Green, J., Potter, J. D., Lindblom, A., Lagerstedt, K., Thibodeau, S. N., Lindor, N. M., Young, J., Winship, I., Dowty, J. G., White, D. M., Hopper, J. L., Baglietto, L., Jenkins, M. A., de la Chapelle, A. <strong>The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.</strong> Gastroenterology 135: 419-428, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18602922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18602922</a>] [<a href="https://doi.org/10.1053/j.gastro.2008.04.026" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18602922">Senter et al. (2008)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18602922+25856668" 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>Heterozygous mutation in the PMS2 gene causes HNPCC4. For a more complete discussion of the molecular genetics of HNPCC4, see <a href="/entry/600259">600259</a>.</p>
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<p>Among 12 presumably unrelated probands with HNPCC in whom <a href="#1" class="mim-tip-reference" title="Clendenning, M., Senter, L., Hampel, H., Robinson, K. L., Sun, S., Buchanan, D., Walsh, M. D., Nilbert, M., Green, J., Potter, J., Lindblom, A., de la Chapelle, A. <strong>A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome.</strong> J. Med. Genet. 45: 340-345, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18178629[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/10.1136/jmg.2007.056150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18178629">Clendenning et al. (2008)</a> identified a heterozygous insertion/deletion mutation in the PMS2 gene (<a href="/entry/600259#0015">600259.0015</a>), family history suggested reduced penetrance. Mean age at diagnosis among probands was 52 years. Haplotype analysis indicated a common founder, and the age of the mutation was estimated at 1,625 years, suggesting that this indel mutation arose sometime during the first millennium. The mutation was enriched in patients of British and Swedish ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18178629" 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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Clendenning, M., Senter, L., Hampel, H., Robinson, K. L., Sun, S., Buchanan, D., Walsh, M. D., Nilbert, M., Green, J., Potter, J., Lindblom, A., de la Chapelle, A.
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J. Med. Genet. 45: 340-345, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18178629[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=18178629" 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.2007.056150" target="_blank">Full Text</a>]
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Goodenberger, M. L., Thomas, B. C., Riegert-Johnson, D., Boland, C. R., Plon, S. E., Clendenning, M., Win, A. K., Senter, L., Lipkin, S. M., Stadler, Z. K., Macrae, F. A., Lynch, H. T., and 18 others.
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<strong>PMS2 monoallelic mutation carriers: the known unknown.</strong>
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Genet. Med. 18: 13-19, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25856668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25856668</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25856668" 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/gim.2015.27" target="_blank">Full Text</a>]
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Hendriks, Y. M. C., Jagmohan-Changur, S., Van der Klift, H. M., Morreau, H., Van Puijenbroek, M., Tops, C., Van Os, T., Wagner, A., Ausems, M. G. F. M., Gomez, E., Breuning, M. J., Brocker-Vriends, A. H. J. T., Vasen, H. F. A., Wijnen, J. T.
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<strong>Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).</strong>
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Gastroenterology 130: 312-322, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16472587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16472587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16472587" 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/10.1053/j.gastro.2005.10.052" target="_blank">Full Text</a>]
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Nicolaides, N. C., Papadopoulos, N., Liu, B., Wei, Y.-F., Carter, K. C., Ruben, S. M., Rosen, C. A., Haseltine, W. A., Fleischmann, R. D., Fraser, C. M., Adams, M. D., Venter, J. C., Dunlop, M. G., Hamilton, S. R., Petersen, G. M., de la Chapelle, A., Vogelstein, B., Kinzler, K. W.
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<strong>Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.</strong>
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Nature 371: 75-80, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8072530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8072530</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8072530" 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/10.1038/371075a0" target="_blank">Full Text</a>]
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Senter, L., Clendenning, M., Sotamaa, K., Hampel, H., Green, J., Potter, J. D., Lindblom, A., Lagerstedt, K., Thibodeau, S. N., Lindor, N. M., Young, J., Winship, I., Dowty, J. G., White, D. M., Hopper, J. L., Baglietto, L., Jenkins, M. A., de la Chapelle, A.
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<strong>The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.</strong>
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Gastroenterology 135: 419-428, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18602922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18602922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18602922" 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/10.1053/j.gastro.2008.04.026" target="_blank">Full Text</a>]
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Thompson, E., Meldrum, C. J., Crooks, R., McPhillips, M., Thomas, L., Spigelman, A. D., Scott, R. J.
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<strong>Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.</strong>
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Clin. Genet. 65: 215-225, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14756672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14756672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14756672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2004.00214.x" target="_blank">Full Text</a>]
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Worthley, D. L., Walsh, M. D., Barker, M., Ruszkiewicz, A., Bennett, G., Phillips, K., Suthers, G.
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<strong>Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer.</strong>
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Gastroenterology 128: 1431-1436, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887124</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887124" 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/10.1053/j.gastro.2005.04.008" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 2/23/2016
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Anne M. Stumpf : 11/8/2011
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carol : 11/16/2022
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carol : 11/15/2022<br>joanna : 06/29/2016<br>alopez : 2/23/2016<br>carol : 10/9/2013<br>ckniffin : 9/23/2013<br>alopez : 11/9/2011
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COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 4; HNPCC4
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<strong>ORPHA:</strong> 144;
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<strong>DO:</strong> 0070275;
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<strong>Phenotype-Gene Relationships</strong>
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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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7p22.1
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Lynch syndrome 4
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614337
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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 Lynch syndrome-4 (LYNCH4), also known as hereditary nonpolyposis colorectal cancer type 4 (HNPCC4), is caused by heterozygous mutation in the PMS2 gene (600259) on chromosome 7p22.</p><p>For a discussion of genetic heterogeneity of Lynch syndrome, see 120435.</p>
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<strong>Description</strong>
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<p>Lynch syndrome-4 (LYNCH4), or hereditary nonpolyposis colorectal cancer type 4 (HNPCC4), is an autosomal dominant disorder characterized primarily by the development of early-onset colorectal cancer. It is associated with the development of a variety of epithelial tumors that include endometrial cancer, stomach cancer, and ovarian cancer (summary by Thompson et al., 2004). </p>
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<p>Nicolaides et al. (1994) identified a germline deletion in the PMS2 gene in a patient with a family history of HNPCC. A second deletion was found in the patient's tumor sample. The tumor from this patient exhibited microsatellite instability. </p><p>To examine the contribution of the PMS2 and EXO1 (606063) genes to the HNPCC disease phenotype, Thompson et al. (2004) studied 21 families negative for mutations in MSH2 (609309) and MLH1 (120436) that fulfilled the Amsterdam diagnostic criteria. They found that mutation in PMS2 accounts for only a small proportion of HNPCC families. </p><p>Worthley et al. (2005) tested a cohort of 80 patients with features suggestive of HNPCC for evidence of defective mismatch repair and exclusive loss of expression of the PMS2 gene in the tumor. They identified a family with HNPCC due to autosomal dominant inheritance of a loss-of-function mutation in the PMS2 gene and stated that this was the first description of such a kindred. The proband had been diagnosed with cancer of the transverse colon at 49 years of age. Two years later he developed and subsequently died of metastatic esophageal adenocarcinoma. His mother developed endometrial cancer at 60 years of age and carcinoma of the cecum at age 80 years. His maternal grandfather and great-uncle developed colorectal cancer at 66 and 45 years of age, respectively. The brother of the proband had 2 sessile polyps removed from the sigmoid colon, 1 at age 47 and the other at age 49. A maternal uncle died of metastatic squamous cell carcinoma of the esophagus, and his daughter developed breast cancer at the age of 25 years. </p><p>Hendriks et al. (2006) summarized the phenotype of 7 families with colorectal cancer and a truncating mutation in the PMS2 gene. Although only 3 of the 7 families fulfilled the Amsterdam criteria, in 6 of the 7 families, the pattern of inheritance appeared to be autosomal dominant. The most frequently observed cancer in proven mutation carriers was colorectal carcinoma, followed by endometrial carcinoma and ovarian carcinoma. The mean age at diagnosis was 52 years, approximately 7 to 8 years higher than the mean age of diagnosis observed in families associated with MLH1 and MSH2 mutations. Hendriks et al. (2006) hypothesized that the attenuated phenotype of families with PMS2 mutations may be explained by the fact that in the absence of PMS2, a functional MLH1 and MLH3 (604395) heterodimeric protein can be formed that is able to repair DNA mismatches. In families with MLH1 or MSH2 gene defects, no alternative heterodimers can be created, with consequently a complete inactivation of the mismatch repair system with massive microsatellite instability and a higher risk of cancer. </p><p>Goodenberger et al. (2016) examined the penetrance and presentation of colorectal cancer in 234 monoallelic PMS2 mutation carriers from 170 families. Approximately 8% of those with colorectal cancer were diagnosed before age 30, and each of these tumors presented on the left side of the colon. As it was unknown what causes the early onset of colorectal cancer in some families with monoallelic PMS2 germline mutations, the authors recommended against reducing cancer surveillance guidelines in families found to have monoallelic PMS2 mutations, in spite of the reduced penetrance (15-20%, according to Senter et al. (2008)). </p>
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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>Heterozygous mutation in the PMS2 gene causes HNPCC4. For a more complete discussion of the molecular genetics of HNPCC4, see 600259.</p>
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<strong>Population Genetics</strong>
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<p>Among 12 presumably unrelated probands with HNPCC in whom Clendenning et al. (2008) identified a heterozygous insertion/deletion mutation in the PMS2 gene (600259.0015), family history suggested reduced penetrance. Mean age at diagnosis among probands was 52 years. Haplotype analysis indicated a common founder, and the age of the mutation was estimated at 1,625 years, suggesting that this indel mutation arose sometime during the first millennium. The mutation was enriched in patients of British and Swedish ancestry. </p>
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<strong>REFERENCES</strong>
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</h4>
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Clendenning, M., Senter, L., Hampel, H., Robinson, K. L., Sun, S., Buchanan, D., Walsh, M. D., Nilbert, M., Green, J., Potter, J., Lindblom, A., de la Chapelle, A.
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<strong>A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome.</strong>
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J. Med. Genet. 45: 340-345, 2008.
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[PubMed: 18178629]
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[Full Text: https://doi.org/10.1136/jmg.2007.056150]
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Goodenberger, M. L., Thomas, B. C., Riegert-Johnson, D., Boland, C. R., Plon, S. E., Clendenning, M., Win, A. K., Senter, L., Lipkin, S. M., Stadler, Z. K., Macrae, F. A., Lynch, H. T., and 18 others.
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<strong>PMS2 monoallelic mutation carriers: the known unknown.</strong>
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Genet. Med. 18: 13-19, 2016.
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[PubMed: 25856668]
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[Full Text: https://doi.org/10.1038/gim.2015.27]
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Hendriks, Y. M. C., Jagmohan-Changur, S., Van der Klift, H. M., Morreau, H., Van Puijenbroek, M., Tops, C., Van Os, T., Wagner, A., Ausems, M. G. F. M., Gomez, E., Breuning, M. J., Brocker-Vriends, A. H. J. T., Vasen, H. F. A., Wijnen, J. T.
|
|
<strong>Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).</strong>
|
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Gastroenterology 130: 312-322, 2006.
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[PubMed: 16472587]
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[Full Text: https://doi.org/10.1053/j.gastro.2005.10.052]
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Nicolaides, N. C., Papadopoulos, N., Liu, B., Wei, Y.-F., Carter, K. C., Ruben, S. M., Rosen, C. A., Haseltine, W. A., Fleischmann, R. D., Fraser, C. M., Adams, M. D., Venter, J. C., Dunlop, M. G., Hamilton, S. R., Petersen, G. M., de la Chapelle, A., Vogelstein, B., Kinzler, K. W.
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<strong>Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.</strong>
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Nature 371: 75-80, 1994.
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[PubMed: 8072530]
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[Full Text: https://doi.org/10.1038/371075a0]
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<li>
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<p class="mim-text-font">
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Senter, L., Clendenning, M., Sotamaa, K., Hampel, H., Green, J., Potter, J. D., Lindblom, A., Lagerstedt, K., Thibodeau, S. N., Lindor, N. M., Young, J., Winship, I., Dowty, J. G., White, D. M., Hopper, J. L., Baglietto, L., Jenkins, M. A., de la Chapelle, A.
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<strong>The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.</strong>
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Gastroenterology 135: 419-428, 2008.
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[PubMed: 18602922]
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[Full Text: https://doi.org/10.1053/j.gastro.2008.04.026]
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<p class="mim-text-font">
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Thompson, E., Meldrum, C. J., Crooks, R., McPhillips, M., Thomas, L., Spigelman, A. D., Scott, R. J.
|
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<strong>Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.</strong>
|
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Clin. Genet. 65: 215-225, 2004.
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[PubMed: 14756672]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2004.00214.x]
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Worthley, D. L., Walsh, M. D., Barker, M., Ruszkiewicz, A., Bennett, G., Phillips, K., Suthers, G.
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<strong>Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer.</strong>
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Gastroenterology 128: 1431-1436, 2005.
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[PubMed: 15887124]
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[Full Text: https://doi.org/10.1053/j.gastro.2005.04.008]
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