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Entry
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- #619555 - EPIDERMOLYSIS BULLOSA SIMPLEX 2A, GENERALIZED SEVERE; EBS2A
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- OMIM
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<p>
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<span class="h4">#619555</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="/clinicalSynopsis/619555"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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<a href="/phenotypicSeries/PS131760"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=EPIDERMOLYSIS BULLOSA SIMPLEX 2A, GENERALIZED SEVERE" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11422&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1369/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=619555[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=79396" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 79396<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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619555
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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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EPIDERMOLYSIS BULLOSA SIMPLEX 2A, GENERALIZED SEVERE; EBS2A
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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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EPIDERMOLYSIS BULLOSA SIMPLEX 2A, DOWLING-MEARA TYPE
|
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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>
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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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<tr class="active">
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/12/410?start=-3&limit=10&highlight=410">
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12q13.13
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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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Epidermolysis bullosa simplex 2A, generalized severe
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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/619555"> 619555 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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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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KRT5
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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/148040"> 148040 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/619555" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS131760" 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/619555" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/619555" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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|
|
- Autosomal 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> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Intraoral mucosal blistering <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5678247&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5678247</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Larynx </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Laryngomalacia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38086007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38086007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0264303&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0264303</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001601" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001601</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001601" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001601</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Airways </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Bronchomalacia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54203008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54203008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233788001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233788001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0264353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0264353</a>, <a href="https://bioportal.bioontology.org/search?q=C0340231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002780" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002780</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002786" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002786</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002780" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002780</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Severe neonatal oral blistering <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5678245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5678245</a>]</span><br /> -
|
|
Poor feeding, requiring gastrostomy tube placement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5678246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5678246</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Blisters and erosions over entire body <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5678248&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5678248</a>]</span><br /> -
|
|
Herpetiform spreading with central healing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5678249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5678249</a>]</span><br /> -
|
|
Minimal to no scarring <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5562894&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5562894</a>]</span><br /> -
|
|
Palmoplantar hyperkeratosis <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L85.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L85.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022596&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022596</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000972" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000972</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000972" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000972</a>]</span><br /> -
|
|
Aplasia cutis congenita (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254237003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254237003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35484002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35484002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q84.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q84.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0282160&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0282160</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001057" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001057</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001057" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001057</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Electron Microscopy </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cleavage within basal cell layer <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5678250&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5678250</a>]</span><br /> -
|
|
Clumping of keratin tonofilaments <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5676664&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5676664</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034067</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nails </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dystrophic nails <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87065009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87065009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L60.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L60.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221260</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008404</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008404</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Developmental delays (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> VOICE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hoarse cry (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2678303&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2678303</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001615" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001615</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001615" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001615</a>]</span><br />
|
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|
|
</span>
|
|
</div>
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|
|
|
</div>
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|
</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset at birth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836142&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836142</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003577" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003577</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003577" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003577</a>]</span><br /> -
|
|
Exacerbation during the summer (in some patients)<br /> -
|
|
Improvement with age<br /> -
|
|
Patients with the E477K substitution (<a href="/entry/148040#0025">148040.0025</a>) have a more severe course that is sometimes fatal in infancy (see <a href="/entry/148040#0025">148040.0025</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
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|
|
</div>
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|
|
</div>
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<div>
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the keratin 5 gene (KRT5, <a href="/entry/148040#0001">148040.0001</a>)<br />
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|
|
</span>
|
|
</div>
|
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|
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</div>
|
|
|
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</div>
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|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
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|
|
|
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|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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|
|
|
|
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|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Epidermolysis bullosa simplex
|
|
- <a href="/phenotypicSeries/PS131760">PS131760</a>
|
|
- 18 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/3/900?start=-3&limit=10&highlight=900"> 3q27.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617294"> Epidermolysis bullosa simplex 6, generalized intermediate, with or without cardiomyopathy </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/617294"> 617294 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611295"> KLHL24 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611295"> 611295 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/611?start=-3&limit=10&highlight=611"> 6p12.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615425"> Epidermolysis bullosa simplex 3, localized or generalized intermediate, with bp230 deficiency </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615425"> 615425 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/113810"> DST </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/113810"> 113810 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/621?start=-3&limit=10&highlight=621"> 8q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/226670"> Epidermolysis bullosa simplex 5B, with muscular dystrophy </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/226670"> 226670 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> PLEC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> 601282 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/621?start=-3&limit=10&highlight=621"> 8q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616487"> ?Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616487"> 616487 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> PLEC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> 601282 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/621?start=-3&limit=10&highlight=621"> 8q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/131950"> Epidermolysis bullosa simplex 5A, Ogna type </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/131950"> 131950 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> PLEC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> 601282 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/621?start=-3&limit=10&highlight=621"> 8q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612138"> Epidermolysis bullosa simplex 5C, with pyloric atresia </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612138"> 612138 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> PLEC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601282"> 601282 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/48?start=-3&limit=10&highlight=48"> 11p15.5 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609057"> Epidermolysis bullosa simplex 7, with nephropathy and deafness </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609057"> 609057 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602243"> CD151 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602243"> 602243 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/899?start=-3&limit=10&highlight=899"> 11q22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615028"> Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615028"> 615028 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612878"> EXPH5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612878"> 612878 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/410?start=-3&limit=10&highlight=410"> 12q13.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609352"> Epidermolysis bullosa simplex 2E, with migratory circinate erythema </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/609352"> 609352 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/148040"> KRT5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/148040"> 148040 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/410?start=-3&limit=10&highlight=410"> 12q13.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619588"> Epidermolysis bullosa simplex 2B, generalized intermediate </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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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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<a href="/entry/619588"> 619588 </a>
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<span class="mim-font">
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<a href="/entry/148040"> KRT5 </a>
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<span class="mim-font">
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<a href="/entry/148040"> 148040 </a>
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<a href="/geneMap/12/410?start=-3&limit=10&highlight=410"> 12q13.13 </a>
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<span class="mim-font">
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<a href="/entry/131960"> Epidermolysis bullosa simplex 2F, with mottled pigmentation </a>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/131960"> 131960 </a>
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<span class="mim-font">
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<a href="/entry/148040"> KRT5 </a>
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<span class="mim-font">
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<a href="/entry/148040"> 148040 </a>
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<a href="/geneMap/12/410?start=-3&limit=10&highlight=410"> 12q13.13 </a>
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<span class="mim-font">
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<a href="/entry/619555"> Epidermolysis bullosa simplex 2A, generalized severe </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/619555"> 619555 </a>
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<span class="mim-font">
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<a href="/entry/148040"> KRT5 </a>
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<span class="mim-font">
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<a href="/entry/148040"> 148040 </a>
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<a href="/geneMap/12/410?start=-3&limit=10&highlight=410"> 12q13.13 </a>
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<span class="mim-font">
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<a href="/entry/619599"> Epidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span 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 class="mim-font">
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<a href="/entry/619599"> 619599 </a>
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<span class="mim-font">
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<a href="/entry/148040"> KRT5 </a>
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<span class="mim-font">
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<a href="/entry/148040"> 148040 </a>
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<a href="/geneMap/12/410?start=-3&limit=10&highlight=410"> 12q13.13 </a>
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<span class="mim-font">
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<a href="/entry/619594"> Epidermolysis bullosa simplex 2C, localized </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/619594"> 619594 </a>
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<span class="mim-font">
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<a href="/entry/148040"> KRT5 </a>
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<span class="mim-font">
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<a href="/entry/148040"> 148040 </a>
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<span class="mim-font">
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<a href="/geneMap/17/549?start=-3&limit=10&highlight=549"> 17q21.2 </a>
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<span class="mim-font">
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<a href="/entry/131800"> Epidermolysis bullosa simplex 1C, localized </a>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/131800"> 131800 </a>
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<span class="mim-font">
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<a href="/entry/148066"> KRT14 </a>
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<span class="mim-font">
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<a href="/entry/148066"> 148066 </a>
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<span class="mim-font">
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<a href="/geneMap/17/549?start=-3&limit=10&highlight=549"> 17q21.2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/131760"> Epidermolysis bullosa simplex 1A, generalized severe </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/131760"> 131760 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/148066"> KRT14 </a>
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<span class="mim-font">
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<a href="/entry/148066"> 148066 </a>
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<a href="/geneMap/17/549?start=-3&limit=10&highlight=549"> 17q21.2 </a>
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<span class="mim-font">
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<a href="/entry/601001"> Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive </a>
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</span>
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</td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span 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 class="mim-font">
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<a href="/entry/601001"> 601001 </a>
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<span class="mim-font">
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<a href="/entry/148066"> KRT14 </a>
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<span class="mim-font">
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<a href="/entry/148066"> 148066 </a>
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<a href="/geneMap/17/549?start=-3&limit=10&highlight=549"> 17q21.2 </a>
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<span class="mim-font">
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<a href="/entry/131900"> Epidermolysis bullosa simplex 1B, generalized intermediate </a>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/131900"> 131900 </a>
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<span class="mim-font">
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<a href="/entry/148066"> KRT14 </a>
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<span class="mim-font">
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<a href="/entry/148066"> 148066 </a>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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<a id="text" class="mim-anchor"></a>
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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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<p>A number sign (#) is used with this entry because generalized severe epidermolysis bullosa simplex-2A (EBS2A) is caused by heterozygous mutation in the KRT5 gene (<a href="/entry/148040">148040</a>) on chromosome 12q13.</p><p>Another form of generalized severe EBS, EBS1A (<a href="/entry/131760">131760</a>), is caused by mutation in the KRT14 gene (<a href="/entry/148066">148066</a>).</p>
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<a id="description" class="mim-anchor"></a>
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<strong>Description</strong>
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<p>Generalized severe epidermolysis bullosa simplex-2A (EBS2A) is an autosomal dominant skin disorder characterized by extensive intraepidermal blistering after minor mechanical stress from the time of birth with herpetiform marginal spreading and central healing. Oral mucosal involvement, nail dystrophy, onychogryposis, formation of milia, and palmoplantar hyperkeratosis are common features. Blistering is more frequent in warm weather and generally improves with advancing age. The 'severe' subtype of EBS was previously known as the Dowling-Meara type (EBSDM). In addition to the intraepidermal blister formation after minor mechanical stress common to all forms of EBS, skin biopsies from patients with the severe EBS subtype show aggregation and clumping of basal keratins on electron microscopy, resulting in a total collapse of the keratin cytoskeleton of basal keratinocytes (summary by <a href="#4" class="mim-tip-reference" title="Muller, F. B., Anton-Lamprecht, I., Kuster, W., Korge, B. P. <strong>A premature stop codon mutation in the 2B helix termination peptide of keratin 5 in a German epidermolysis bullosa simplex Dowling-Meara case.</strong> J. Invest. Derm. 112: 988-990, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383750</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1999.00615.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383750">Muller et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a discussion of genetic heterogeneity of the subtypes of EBS, see EBS1A (<a href="/entry/131760">131760</a>).</p>
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<strong>Clinical Features</strong>
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<p><a href="#5" class="mim-tip-reference" title="Nomura, K., Shimizu, H., Meng, X., Umeki, K., Tamai, K., Sawamura, D., Nagao, K., Kawakami, T., Nishikawa, T., Hashimoto, I. <strong>A novel keratin K5 mutation in Dowling-Meara epidermolysis bullosa simplex.</strong> J. Invest. Derm. 107: 253-254, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757772</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12329741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8757772">Nomura et al. (1996)</a> reported a Japanese boy with EBS Dowling-Meara (EBSDM) and mutation in the KRT5 gene who developed blisters over the entire body after birth. At 6 days of age, extensive blisters and erosions were present over the entire body and in oral mucous membranes. On clinical grounds, the more severe EB subtypes junctional (see <a href="/entry/226650">226650</a>) or dystrophic (see <a href="/entry/131750">131750</a>) were suspected. After a few months, palmar and plantar hyperkeratosis developed, as well as deformities on all nails. There was no family history of blistering disease. Electron microscopy revealed blisters within basal cells and clumping of tonofilaments characteristic of EBSDM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8757772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Rugg, E. L., Rachet-Prehu, M.-O., Rochat, A., Barrandon, Y., Goossens, M., Lane, E. B., Hovnanian, A. <strong>Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.</strong> Europ. J. Hum. Genet. 7: 293-300, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10234505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10234505</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10234505">Rugg et al. (1999)</a> studied a family of French ancestry with EBS Dowling-Meara type and mutation in the KRT5 gene. All affected individuals had suffered since birth from recurrent and general blistering after mild physical trauma. Blistering was nonscarring and occurred at any body site, but predominantly on hands, elbows, feet, knees, and face. Oral blistering was sometimes noted. Moderate hyperkeratosis of palms and soles was present in several affected individuals. Disease exacerbation was observed during the summer. No milia were noted, and hair, nails, and teeth were normal. Electron microscopic examination of a skin biopsy obtained after rubbing an intact area showed cleavage within the basal keratinocytes with clumping of keratin filaments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10234505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Muller, F. B., Anton-Lamprecht, I., Kuster, W., Korge, B. P. <strong>A premature stop codon mutation in the 2B helix termination peptide of keratin 5 in a German epidermolysis bullosa simplex Dowling-Meara case.</strong> J. Invest. Derm. 112: 988-990, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383750</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1999.00615.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383750">Muller et al. (1999)</a> reported a 38-year-old woman with a mutation in KRT5 who had been affected since birth by generalized blister formation with herpetiform spreading and central healing. Hemorrhagic blisters occurred on the trunk, palms and soles, face, and in oral mucosa after minor trauma. Palmar and plantar hyperkeratoses existed before walking, and plantar hyperkeratoses were painful in periods of blistering. Subungual blisters and irregular nail plate thickening were present. Although some improvement was noted after age 4 years, recurrent generalized blistering occurred into adulthood. Blistering in the basal layer and clumping of basal keratins seen on electron microscopy permitted the diagnosis of EBSDM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383750" 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="Shemanko, C. S., Horn, H. M., Keohane, S. G., Hepburn, N., Kerr, A. I. G., Atherton, D. J., Tidman, M. J., Lane, E. B. <strong>Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential.</strong> Brit. J. Derm. 142: 315-320, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10730767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10730767</a>] [<a href="https://doi.org/10.1046/j.1365-2133.2000.03304.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10730767">Shemanko et al. (2000)</a> described a female infant (patient 2) with Dowling-Meara EBS and mutation in the KRT5 gene who had a hoarse cry, a feature not well documented in Dowling-Meara EBS but usually associated with junctional EB. At birth, patient 2 had blisters on palms and soles, and within hours blistering had spread to involve the tongue, buccal mucosa, periungual regions, and large areas of skin. By 3 weeks of age she had developed stridor and a hoarse cry, which was present until about the age of 2 years. Laryngoscopy was not undertaken. At the age of 19 months, the child developed a widespread cutaneous herpes simplex infection, requiring inpatient treatment with systemic aciclovir. At 5 years of age, the patient was developing normally despite the persistence of widespread herpetiform blistering. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10730767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Glu477 to Lys Mutation</em></strong></p><p>
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<a href="#7" class="mim-tip-reference" title="Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C. <strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong> J. Invest. Derm. 136: 719-721, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26743602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26743602</a>] [<a href="https://doi.org/10.1016/j.jid.2015.11.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26743602">Sathishkumar et al. (2016)</a> and <a href="#2" class="mim-tip-reference" title="Lalor, L., Titeux, M., Palisson, F., Fuentes, I., Yubero, M. J., Tasanen, K., Huilaja, L., Has, C., Tadini, G., Haggstrom, A. N., Hovnanian, A., Lucky, A. W. <strong>Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: genotype-phenotype correlation and in silico modeling analysis.</strong> Pediat. Derm. 36: 132-138, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30515866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30515866</a>] [<a href="https://doi.org/10.1111/pde.13722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30515866">Lalor et al. (2019)</a> reported patients with particularly severe generalized EBS, including skin loss requiring intensive care; several patients died in the first months of life. All of these patients carried a E477K mutation in KRT5 (see MOLECULAR GENETICS). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26743602+30515866" 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="Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C. <strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong> J. Invest. Derm. 136: 719-721, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26743602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26743602</a>] [<a href="https://doi.org/10.1016/j.jid.2015.11.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26743602">Sathishkumar et al. (2016)</a> reported 7 children and 1 adult with severe generalized EBS. All 7 children had extensive skin loss at birth and required intensive medical care, and 5 of them died within the first 6 months of life, having received parenteral feeding, opiate analgesia, and antibiotics until death. Of the 2 surviving infants, one was a 4-year-old girl, and the other was still hospitalized at day 86 of life, with hoarseness, feeding difficulties, and recurrent skin infections. Four of the deceased infants had no family history of EBS, but 1 had an affected mother who had severe blistering in childhood and in adulthood experienced marked palmoplantar keratoderma with significant pain and recurrent infections restricting mobility, as well as severe periodontal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26743602" 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="Lalor, L., Titeux, M., Palisson, F., Fuentes, I., Yubero, M. J., Tasanen, K., Huilaja, L., Has, C., Tadini, G., Haggstrom, A. N., Hovnanian, A., Lucky, A. W. <strong>Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: genotype-phenotype correlation and in silico modeling analysis.</strong> Pediat. Derm. 36: 132-138, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30515866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30515866</a>] [<a href="https://doi.org/10.1111/pde.13722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30515866">Lalor et al. (2019)</a> reported 6 children with severe generalized EBS. All 6 patients had severe generalized blistering and aplasia cutis and required intensive care after birth, and 1 child died at age 1 month due to sepsis. Blistering improved with age, and surviving children developed a distinctive reticulated skin pattern that was erythematous, hyperpigmented, or both, with round blanched patches of skin centrally. Most patients had severe onychodystrophy with moderate to severe palmoplantar hyperkeratosis. Often there was severe neonatal oral blistering and poor weight gain, necessitating gastrostomy tube placement. Two patients had broncho- and/or laryngomalacia, requiring tracheostomy. In addition, most patients had multiple developmental delays, beyond what might be expected for a chronically ill child. The authors noted that the reticulated pattern of pigmentation in these patients appeared to be distinct and perhaps pathognomonic, and stated that it was different from the pigmentation observed in EBS with mottled pigmentation (EBSMP; <a href="/entry/131960">131960</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30515866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of EBS2A in the families reported by <a href="#3" class="mim-tip-reference" title="Lane, E. B., Rugg, E. L., Navsaria, H., Leigh, I. M., Heagerty, A. H. M., Ishida-Yamamoto, A., Eady, R. A. J. <strong>A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering.</strong> Nature 356: 244-246, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1372711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1372711</a>] [<a href="https://doi.org/10.1038/356244a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1372711">Lane et al. (1992)</a> and <a href="#6" class="mim-tip-reference" title="Rugg, E. L., Rachet-Prehu, M.-O., Rochat, A., Barrandon, Y., Goossens, M., Lane, E. B., Hovnanian, A. <strong>Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.</strong> Europ. J. Hum. Genet. 7: 293-300, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10234505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10234505</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10234505">Rugg et al. (1999)</a> was consistent with autosomal dominant inheritance. The heterozygous mutations in the KRT5 gene that were identified in patients with EBS2A by <a href="#5" class="mim-tip-reference" title="Nomura, K., Shimizu, H., Meng, X., Umeki, K., Tamai, K., Sawamura, D., Nagao, K., Kawakami, T., Nishikawa, T., Hashimoto, I. <strong>A novel keratin K5 mutation in Dowling-Meara epidermolysis bullosa simplex.</strong> J. Invest. Derm. 107: 253-254, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757772</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12329741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8757772">Nomura et al. (1996)</a> and <a href="#4" class="mim-tip-reference" title="Muller, F. B., Anton-Lamprecht, I., Kuster, W., Korge, B. P. <strong>A premature stop codon mutation in the 2B helix termination peptide of keratin 5 in a German epidermolysis bullosa simplex Dowling-Meara case.</strong> J. Invest. Derm. 112: 988-990, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383750</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1999.00615.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383750">Muller et al. (1999)</a> occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10234505+1372711+8757772+10383750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large family with Dowling-Meara EBS, <a href="#3" class="mim-tip-reference" title="Lane, E. B., Rugg, E. L., Navsaria, H., Leigh, I. M., Heagerty, A. H. M., Ishida-Yamamoto, A., Eady, R. A. J. <strong>A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering.</strong> Nature 356: 244-246, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1372711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1372711</a>] [<a href="https://doi.org/10.1038/356244a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1372711">Lane et al. (1992)</a> identified a heterozygous mutation in the KRT5 gene (E475G; <a href="/entry/148040#0001">148040.0001</a>) that segregated with the disorder in an autosomal dominant pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1372711" 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 Japanese patient with EBSDM, <a href="#5" class="mim-tip-reference" title="Nomura, K., Shimizu, H., Meng, X., Umeki, K., Tamai, K., Sawamura, D., Nagao, K., Kawakami, T., Nishikawa, T., Hashimoto, I. <strong>A novel keratin K5 mutation in Dowling-Meara epidermolysis bullosa simplex.</strong> J. Invest. Derm. 107: 253-254, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757772</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12329741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8757772">Nomura et al. (1996)</a> detected a de novo heterozygous missense mutation in the KRT5 gene (<a href="/entry/148040#0008">148040.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8757772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a large French family with Dowling-Meara EBS, <a href="#6" class="mim-tip-reference" title="Rugg, E. L., Rachet-Prehu, M.-O., Rochat, A., Barrandon, Y., Goossens, M., Lane, E. B., Hovnanian, A. <strong>Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.</strong> Europ. J. Hum. Genet. 7: 293-300, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10234505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10234505</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10234505">Rugg et al. (1999)</a> identified a heterozygous splice site mutation in the KRT5 gene (<a href="/entry/148040#0011">148040.0011</a>), resulting in a deletion of the last 5 amino acids of the H1 head domain and the first 17 amino acids of the conserved N-terminal end of the 1A rod domain, including the first 2 heptad repeats and the helix initiation peptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10234505" 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 5-year-old girl with Dowling-Meara EBS and a hoarse cry, <a href="#8" class="mim-tip-reference" title="Shemanko, C. S., Horn, H. M., Keohane, S. G., Hepburn, N., Kerr, A. I. G., Atherton, D. J., Tidman, M. J., Lane, E. B. <strong>Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential.</strong> Brit. J. Derm. 142: 315-320, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10730767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10730767</a>] [<a href="https://doi.org/10.1046/j.1365-2133.2000.03304.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10730767">Shemanko et al. (2000)</a> identified a heterozygous missense mutation in the KRT5 gene (S181P; <a href="/entry/148040#0012">148040.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10730767" 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 38-year-old German woman with EBSDM, <a href="#4" class="mim-tip-reference" title="Muller, F. B., Anton-Lamprecht, I., Kuster, W., Korge, B. P. <strong>A premature stop codon mutation in the 2B helix termination peptide of keratin 5 in a German epidermolysis bullosa simplex Dowling-Meara case.</strong> J. Invest. Derm. 112: 988-990, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383750</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1999.00615.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383750">Muller et al. (1999)</a> detected a heterozygous nonsense mutation in the KRT5 gene (E477X; <a href="/entry/148040#0015">148040.0015</a>). The patient's unaffected parents, 2 sisters, and son did not carry the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Glu477 to Lys Mutation</em></strong></p><p>
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<a href="#7" class="mim-tip-reference" title="Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C. <strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong> J. Invest. Derm. 136: 719-721, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26743602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26743602</a>] [<a href="https://doi.org/10.1016/j.jid.2015.11.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26743602">Sathishkumar et al. (2016)</a> reviewed a cohort of 37 newborns with generalized severe EBS, reported to the National Health Service of the UK over a 15-year period, 33 of whom underwent genetic analysis. Of those 33 patients, 17 had mutations in the KRT5 gene, 15 had mutations in KRT14, and 1 had a mutation in both KRT5 and KRT14. Seven children, including 5 who died in infancy and 1 who remained hospitalized at almost 3 months of age, were heterozygous for an E477K substitution in the KRT5 gene (<a href="/entry/148040#0025">148040.0025</a>). The E477K variant occurred de novo in all but 1 of the children, who had an affected mother. <a href="#7" class="mim-tip-reference" title="Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C. <strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong> J. Invest. Derm. 136: 719-721, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26743602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26743602</a>] [<a href="https://doi.org/10.1016/j.jid.2015.11.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26743602">Sathishkumar et al. (2016)</a> noted that the E477K variant had been reported previously in 10 cases of generalized severe EBS, but clinical information was limited and mortality data were not reported. The authors suggested that the E477K variant might predispose to a severe and potentially lethal form of generalized severe EBS, noting that survivors were likely to be overrepresented if some affected neonates died before genetic studies were performed and the mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26743602" 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="Lalor, L., Titeux, M., Palisson, F., Fuentes, I., Yubero, M. J., Tasanen, K., Huilaja, L., Has, C., Tadini, G., Haggstrom, A. N., Hovnanian, A., Lucky, A. W. <strong>Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: genotype-phenotype correlation and in silico modeling analysis.</strong> Pediat. Derm. 36: 132-138, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30515866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30515866</a>] [<a href="https://doi.org/10.1111/pde.13722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30515866">Lalor et al. (2019)</a> ascertained 6 children from national or local epidermolysis bullosa databases, from the United States, Italy, Germany, Finland, and Chile, in whom Sanger sequencing had revealed heterozygosity for the E477K mutation in the KRT5 gene. All were severely affected and 1 infant died. In 5 patients, the mutation was demonstrated to have arisen de novo; genetic analysis had not yet been performed in the parents of the sixth patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30515866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 15-year review of all infants born with generalized severe EBS and notified to the National Health Service of the UK, <a href="#7" class="mim-tip-reference" title="Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C. <strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong> J. Invest. Derm. 136: 719-721, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26743602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26743602</a>] [<a href="https://doi.org/10.1016/j.jid.2015.11.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26743602">Sathishkumar et al. (2016)</a> identified 37 cases. Genetic analysis in 33 of those cases showed KRT5 mutations in 17, KRT14 mutations in 15, and mutations in both KRT5 and KRT14 in 1 patient. The authors noted that generalized severe EBS was associated with KRT5 and KRT14 mutations involving the highly conserved ends of the alpha-helical rod domain, the helix boundary motifs, whereas mutations outside the helix boundary motifs were associated with milder EBS phenotypes. In addition, clinical severity had been reported to be associated with the nature of the amino acid change, with changes in polarity or acidity being associated with more severe phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26743602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Kim, E. N., Harris, A. G., Bingham, L. J., Yan, W., Su, J. C., Murrell, D. F. <strong>A review of 52 pedigrees with epidermolysis bullosa simplex identifying ten novel mutations in KRT5 and KRT14 in australia.</strong> Acta Derm. Venereol. 97: 1114-1119, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28561874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28561874</a>] [<a href="https://doi.org/10.2340/00015555-2715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28561874">Kim et al. (2017)</a> screened 52 Australian patients with EBS for mutations in the KRT5 and KRT14 genes and identified 32 different mutations in 39 pedigrees. The authors found that mutations causing localized EBS occurred sporadically across the KRT5 and KRT14 peptides. Mutations resulting in generalized severe EBS were most commonly clustered at the helix boundary motifs, the helix initiation (HIP) and termination (HTP) regions, which are critical for normal keratin formation. In most other cases phenotypes correlated with the location of the mutations and were in agreement with previous reports. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28561874" 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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Kim, E. N., Harris, A. G., Bingham, L. J., Yan, W., Su, J. C., Murrell, D. F.
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<strong>A review of 52 pedigrees with epidermolysis bullosa simplex identifying ten novel mutations in KRT5 and KRT14 in australia.</strong>
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Acta Derm. Venereol. 97: 1114-1119, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28561874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28561874</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28561874" 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/10.2340/00015555-2715" target="_blank">Full Text</a>]
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Lalor, L., Titeux, M., Palisson, F., Fuentes, I., Yubero, M. J., Tasanen, K., Huilaja, L., Has, C., Tadini, G., Haggstrom, A. N., Hovnanian, A., Lucky, A. W.
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<strong>Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: genotype-phenotype correlation and in silico modeling analysis.</strong>
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Pediat. Derm. 36: 132-138, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30515866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30515866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30515866" 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/pde.13722" target="_blank">Full Text</a>]
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Lane, E. B., Rugg, E. L., Navsaria, H., Leigh, I. M., Heagerty, A. H. M., Ishida-Yamamoto, A., Eady, R. A. J.
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<strong>A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering.</strong>
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Nature 356: 244-246, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1372711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1372711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1372711" 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/10.1038/356244a0" target="_blank">Full Text</a>]
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Muller, F. B., Anton-Lamprecht, I., Kuster, W., Korge, B. P.
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<strong>A premature stop codon mutation in the 2B helix termination peptide of keratin 5 in a German epidermolysis bullosa simplex Dowling-Meara case.</strong>
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J. Invest. Derm. 112: 988-990, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383750" 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/10.1046/j.1523-1747.1999.00615.x" target="_blank">Full Text</a>]
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Nomura, K., Shimizu, H., Meng, X., Umeki, K., Tamai, K., Sawamura, D., Nagao, K., Kawakami, T., Nishikawa, T., Hashimoto, I.
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<strong>A novel keratin K5 mutation in Dowling-Meara epidermolysis bullosa simplex.</strong>
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J. Invest. Derm. 107: 253-254, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757772</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8757772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Rugg, E. L., Rachet-Prehu, M.-O., Rochat, A., Barrandon, Y., Goossens, M., Lane, E. B., Hovnanian, A.
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<strong>Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.</strong>
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Europ. J. Hum. Genet. 7: 293-300, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10234505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10234505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10234505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C.
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<strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong>
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J. Invest. Derm. 136: 719-721, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26743602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26743602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26743602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Shemanko, C. S., Horn, H. M., Keohane, S. G., Hepburn, N., Kerr, A. I. G., Atherton, D. J., Tidman, M. J., Lane, E. B.
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<strong>Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential.</strong>
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Brit. J. Derm. 142: 315-320, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10730767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10730767</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10730767" 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/10.1046/j.1365-2133.2000.03304.x" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 01/13/2022
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Anne M. Stumpf - updated : 11/11/2021
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Creation Date:
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Anne M. Stumpf : 09/30/2021
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alopez : 01/13/2022
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alopez : 11/11/2021<br>alopez : 11/01/2021<br>alopez : 10/28/2021<br>alopez : 10/26/2021<br>alopez : 10/25/2021<br>alopez : 10/20/2021
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<strong>#</strong> 619555
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EPIDERMOLYSIS BULLOSA SIMPLEX 2A, GENERALIZED SEVERE; EBS2A
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EPIDERMOLYSIS BULLOSA SIMPLEX 2A, DOWLING-MEARA TYPE
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<strong>ORPHA:</strong> 79396;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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12q13.13
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Epidermolysis bullosa simplex 2A, generalized severe
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619555
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Autosomal dominant
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<span class="mim-font">
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3
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KRT5
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148040
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<p>A number sign (#) is used with this entry because generalized severe epidermolysis bullosa simplex-2A (EBS2A) is caused by heterozygous mutation in the KRT5 gene (148040) on chromosome 12q13.</p><p>Another form of generalized severe EBS, EBS1A (131760), is caused by mutation in the KRT14 gene (148066).</p>
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<strong>Description</strong>
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<p>Generalized severe epidermolysis bullosa simplex-2A (EBS2A) is an autosomal dominant skin disorder characterized by extensive intraepidermal blistering after minor mechanical stress from the time of birth with herpetiform marginal spreading and central healing. Oral mucosal involvement, nail dystrophy, onychogryposis, formation of milia, and palmoplantar hyperkeratosis are common features. Blistering is more frequent in warm weather and generally improves with advancing age. The 'severe' subtype of EBS was previously known as the Dowling-Meara type (EBSDM). In addition to the intraepidermal blister formation after minor mechanical stress common to all forms of EBS, skin biopsies from patients with the severe EBS subtype show aggregation and clumping of basal keratins on electron microscopy, resulting in a total collapse of the keratin cytoskeleton of basal keratinocytes (summary by Muller et al., 1999). </p><p>For a discussion of genetic heterogeneity of the subtypes of EBS, see EBS1A (131760).</p>
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<strong>Clinical Features</strong>
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<p>Nomura et al. (1996) reported a Japanese boy with EBS Dowling-Meara (EBSDM) and mutation in the KRT5 gene who developed blisters over the entire body after birth. At 6 days of age, extensive blisters and erosions were present over the entire body and in oral mucous membranes. On clinical grounds, the more severe EB subtypes junctional (see 226650) or dystrophic (see 131750) were suspected. After a few months, palmar and plantar hyperkeratosis developed, as well as deformities on all nails. There was no family history of blistering disease. Electron microscopy revealed blisters within basal cells and clumping of tonofilaments characteristic of EBSDM. </p><p>Rugg et al. (1999) studied a family of French ancestry with EBS Dowling-Meara type and mutation in the KRT5 gene. All affected individuals had suffered since birth from recurrent and general blistering after mild physical trauma. Blistering was nonscarring and occurred at any body site, but predominantly on hands, elbows, feet, knees, and face. Oral blistering was sometimes noted. Moderate hyperkeratosis of palms and soles was present in several affected individuals. Disease exacerbation was observed during the summer. No milia were noted, and hair, nails, and teeth were normal. Electron microscopic examination of a skin biopsy obtained after rubbing an intact area showed cleavage within the basal keratinocytes with clumping of keratin filaments. </p><p>Muller et al. (1999) reported a 38-year-old woman with a mutation in KRT5 who had been affected since birth by generalized blister formation with herpetiform spreading and central healing. Hemorrhagic blisters occurred on the trunk, palms and soles, face, and in oral mucosa after minor trauma. Palmar and plantar hyperkeratoses existed before walking, and plantar hyperkeratoses were painful in periods of blistering. Subungual blisters and irregular nail plate thickening were present. Although some improvement was noted after age 4 years, recurrent generalized blistering occurred into adulthood. Blistering in the basal layer and clumping of basal keratins seen on electron microscopy permitted the diagnosis of EBSDM. </p><p>Shemanko et al. (2000) described a female infant (patient 2) with Dowling-Meara EBS and mutation in the KRT5 gene who had a hoarse cry, a feature not well documented in Dowling-Meara EBS but usually associated with junctional EB. At birth, patient 2 had blisters on palms and soles, and within hours blistering had spread to involve the tongue, buccal mucosa, periungual regions, and large areas of skin. By 3 weeks of age she had developed stridor and a hoarse cry, which was present until about the age of 2 years. Laryngoscopy was not undertaken. At the age of 19 months, the child developed a widespread cutaneous herpes simplex infection, requiring inpatient treatment with systemic aciclovir. At 5 years of age, the patient was developing normally despite the persistence of widespread herpetiform blistering. </p><p><strong><em>Glu477 to Lys Mutation</em></strong></p><p>
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Sathishkumar et al. (2016) and Lalor et al. (2019) reported patients with particularly severe generalized EBS, including skin loss requiring intensive care; several patients died in the first months of life. All of these patients carried a E477K mutation in KRT5 (see MOLECULAR GENETICS). </p><p>Sathishkumar et al. (2016) reported 7 children and 1 adult with severe generalized EBS. All 7 children had extensive skin loss at birth and required intensive medical care, and 5 of them died within the first 6 months of life, having received parenteral feeding, opiate analgesia, and antibiotics until death. Of the 2 surviving infants, one was a 4-year-old girl, and the other was still hospitalized at day 86 of life, with hoarseness, feeding difficulties, and recurrent skin infections. Four of the deceased infants had no family history of EBS, but 1 had an affected mother who had severe blistering in childhood and in adulthood experienced marked palmoplantar keratoderma with significant pain and recurrent infections restricting mobility, as well as severe periodontal disease. </p><p>Lalor et al. (2019) reported 6 children with severe generalized EBS. All 6 patients had severe generalized blistering and aplasia cutis and required intensive care after birth, and 1 child died at age 1 month due to sepsis. Blistering improved with age, and surviving children developed a distinctive reticulated skin pattern that was erythematous, hyperpigmented, or both, with round blanched patches of skin centrally. Most patients had severe onychodystrophy with moderate to severe palmoplantar hyperkeratosis. Often there was severe neonatal oral blistering and poor weight gain, necessitating gastrostomy tube placement. Two patients had broncho- and/or laryngomalacia, requiring tracheostomy. In addition, most patients had multiple developmental delays, beyond what might be expected for a chronically ill child. The authors noted that the reticulated pattern of pigmentation in these patients appeared to be distinct and perhaps pathognomonic, and stated that it was different from the pigmentation observed in EBS with mottled pigmentation (EBSMP; 131960). </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of EBS2A in the families reported by Lane et al. (1992) and Rugg et al. (1999) was consistent with autosomal dominant inheritance. The heterozygous mutations in the KRT5 gene that were identified in patients with EBS2A by Nomura et al. (1996) and Muller et al. (1999) occurred de novo. </p>
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<strong>Molecular Genetics</strong>
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<p>In a large family with Dowling-Meara EBS, Lane et al. (1992) identified a heterozygous mutation in the KRT5 gene (E475G; 148040.0001) that segregated with the disorder in an autosomal dominant pattern. </p><p>In a Japanese patient with EBSDM, Nomura et al. (1996) detected a de novo heterozygous missense mutation in the KRT5 gene (148040.0008). </p><p>In affected members of a large French family with Dowling-Meara EBS, Rugg et al. (1999) identified a heterozygous splice site mutation in the KRT5 gene (148040.0011), resulting in a deletion of the last 5 amino acids of the H1 head domain and the first 17 amino acids of the conserved N-terminal end of the 1A rod domain, including the first 2 heptad repeats and the helix initiation peptide. </p><p>In a 5-year-old girl with Dowling-Meara EBS and a hoarse cry, Shemanko et al. (2000) identified a heterozygous missense mutation in the KRT5 gene (S181P; 148040.0012). </p><p>In a 38-year-old German woman with EBSDM, Muller et al. (1999) detected a heterozygous nonsense mutation in the KRT5 gene (E477X; 148040.0015). The patient's unaffected parents, 2 sisters, and son did not carry the mutation. </p><p><strong><em>Glu477 to Lys Mutation</em></strong></p><p>
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Sathishkumar et al. (2016) reviewed a cohort of 37 newborns with generalized severe EBS, reported to the National Health Service of the UK over a 15-year period, 33 of whom underwent genetic analysis. Of those 33 patients, 17 had mutations in the KRT5 gene, 15 had mutations in KRT14, and 1 had a mutation in both KRT5 and KRT14. Seven children, including 5 who died in infancy and 1 who remained hospitalized at almost 3 months of age, were heterozygous for an E477K substitution in the KRT5 gene (148040.0025). The E477K variant occurred de novo in all but 1 of the children, who had an affected mother. Sathishkumar et al. (2016) noted that the E477K variant had been reported previously in 10 cases of generalized severe EBS, but clinical information was limited and mortality data were not reported. The authors suggested that the E477K variant might predispose to a severe and potentially lethal form of generalized severe EBS, noting that survivors were likely to be overrepresented if some affected neonates died before genetic studies were performed and the mutation occurred de novo. </p><p>Lalor et al. (2019) ascertained 6 children from national or local epidermolysis bullosa databases, from the United States, Italy, Germany, Finland, and Chile, in whom Sanger sequencing had revealed heterozygosity for the E477K mutation in the KRT5 gene. All were severely affected and 1 infant died. In 5 patients, the mutation was demonstrated to have arisen de novo; genetic analysis had not yet been performed in the parents of the sixth patient. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>In a 15-year review of all infants born with generalized severe EBS and notified to the National Health Service of the UK, Sathishkumar et al. (2016) identified 37 cases. Genetic analysis in 33 of those cases showed KRT5 mutations in 17, KRT14 mutations in 15, and mutations in both KRT5 and KRT14 in 1 patient. The authors noted that generalized severe EBS was associated with KRT5 and KRT14 mutations involving the highly conserved ends of the alpha-helical rod domain, the helix boundary motifs, whereas mutations outside the helix boundary motifs were associated with milder EBS phenotypes. In addition, clinical severity had been reported to be associated with the nature of the amino acid change, with changes in polarity or acidity being associated with more severe phenotypes. </p><p>Kim et al. (2017) screened 52 Australian patients with EBS for mutations in the KRT5 and KRT14 genes and identified 32 different mutations in 39 pedigrees. The authors found that mutations causing localized EBS occurred sporadically across the KRT5 and KRT14 peptides. Mutations resulting in generalized severe EBS were most commonly clustered at the helix boundary motifs, the helix initiation (HIP) and termination (HTP) regions, which are critical for normal keratin formation. In most other cases phenotypes correlated with the location of the mutations and were in agreement with previous reports. </p>
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<strong>REFERENCES</strong>
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Kim, E. N., Harris, A. G., Bingham, L. J., Yan, W., Su, J. C., Murrell, D. F.
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<strong>A review of 52 pedigrees with epidermolysis bullosa simplex identifying ten novel mutations in KRT5 and KRT14 in australia.</strong>
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Acta Derm. Venereol. 97: 1114-1119, 2017.
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[PubMed: 28561874]
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[Full Text: https://doi.org/10.2340/00015555-2715]
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Lalor, L., Titeux, M., Palisson, F., Fuentes, I., Yubero, M. J., Tasanen, K., Huilaja, L., Has, C., Tadini, G., Haggstrom, A. N., Hovnanian, A., Lucky, A. W.
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<strong>Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: genotype-phenotype correlation and in silico modeling analysis.</strong>
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Pediat. Derm. 36: 132-138, 2019.
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[PubMed: 30515866]
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[Full Text: https://doi.org/10.1111/pde.13722]
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<p class="mim-text-font">
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Lane, E. B., Rugg, E. L., Navsaria, H., Leigh, I. M., Heagerty, A. H. M., Ishida-Yamamoto, A., Eady, R. A. J.
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<strong>A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering.</strong>
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Nature 356: 244-246, 1992.
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[PubMed: 1372711]
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[Full Text: https://doi.org/10.1038/356244a0]
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Muller, F. B., Anton-Lamprecht, I., Kuster, W., Korge, B. P.
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Nomura, K., Shimizu, H., Meng, X., Umeki, K., Tamai, K., Sawamura, D., Nagao, K., Kawakami, T., Nishikawa, T., Hashimoto, I.
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Rugg, E. L., Rachet-Prehu, M.-O., Rochat, A., Barrandon, Y., Goossens, M., Lane, E. B., Hovnanian, A.
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<strong>Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.</strong>
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Europ. J. Hum. Genet. 7: 293-300, 1999.
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[PubMed: 10234505]
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Sathishkumar, D., Orrin, E., Terron-Kwiatkowski, A., Browne, F., Martinez, A. E., Mellerio, J. E., Ogboli, M., Hoey, S., Ozoemena, L., Liu, L., Baty, D., McGrath, J. A., Moss, C.
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<strong>The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex.</strong>
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[PubMed: 10730767]
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