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Entry
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- *113811 - COLLAGEN, TYPE XVII, ALPHA-1; COL17A1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*113811</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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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="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</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">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/113811">Table View</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>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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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>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000065618;t=ENST00000648076" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=1308" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=113811" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000065618;t=ENST00000648076" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000494" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000494" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=113811" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00223&isoform_id=00223_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/COL17A1" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/179517,179521,1877435,33872847,119569997,119569998,119569999,119829187,146345399,572802391" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q9UMD9" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</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>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=1308" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000065618;t=ENST00000648076" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=COL17A1" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=COL17A1" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+1308" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/COL17A1" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:1308" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1308" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr10&hgg_gene=ENST00000648076.2&hgg_start=104031286&hgg_end=104085880&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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="collapsed 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>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse 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://medlineplus.gov/genetics/gene/col17a1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=113811[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>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=113811[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000065618" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=COL17A1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=COL17A1" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=COL17A1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=COL17A1&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA26710" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:2194" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88450" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/COL17A1#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:88450" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1308/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/results?search_type=advanced&omia_id=001183,002793" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1308" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-7145" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</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>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1308" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=COL17A1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</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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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<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>SNOMEDCT:</strong> 715908008<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="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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113811
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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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COLLAGEN, TYPE XVII, ALPHA-1; COL17A1
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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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BULLOUS PEMPHIGOID ANTIGEN 2; BPAG2<br />
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BP180
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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="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=COL17A1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COL17A1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/10/545?start=-3&limit=10&highlight=545">10q25.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:104031286-104085880&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">10:104,031,286-104,085,880</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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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="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=619787,122400" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
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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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</tr>
|
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</thead>
|
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<tbody>
|
|
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<tr>
|
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<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/10/545?start=-3&limit=10&highlight=545">
|
|
10q25.1
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Epidermolysis bullosa, junctional 4, intermediate
|
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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/619787"> 619787 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<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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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Epithelial recurrent erosion dystrophy
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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/122400"> 122400 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<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">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
|
</td>
|
|
</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>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/113811" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/113811" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
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<p>Collagen XVII, a type II transmembrane protein, is a component of hemidesmosomes, which mediate the adhesion of keratinocytes and other epithelial cells to the underlying basement membrane. Collagen XVII can also be proteolytically shed from the cell surface of keratinocytes to generate a soluble basement membrane collagen (<a href="#11" class="mim-tip-reference" title="Franzke, C.-W., Tasanen, K., Schacke, H., Zhou, Z., Tryggvason, K., Mauch, C., Zigrino, P., Sunnarborg, S., Lee, D. C., Fahrenholz, F., Bruckner-Tuderman, L. <strong>Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs.</strong> EMBO J. 21: 5026-5035, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12356719[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdf532" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12356719">Franzke et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12356719" 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>Autoantibodies present in the sera of patients with bullous pemphigoid (BP) bind to the basement membrane zone. In addition to recognizing the 240-kD basement membrane protein (BP240, or DST; <a href="/entry/113810">113810</a>), they recognize a 180-kD protein in about 50% of all BP sera and in most sera from patients with herpes gestationis. <a href="#7" class="mim-tip-reference" title="Diaz, L. A., Ratrie, H., III, Saunders, W. S., Futamura, S., Squiquera, H. L., Anhalt, G. J., Giudice, G. J. <strong>Isolation of a human epidermal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera: immunolocalization of this protein to the hemidesmosome.</strong> J. Clin. Invest. 86: 1088-1094, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1698819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1698819</a>] [<a href="https://doi.org/10.1172/JCI114812" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1698819">Diaz et al. (1990)</a> isolated a cDNA for the 180-kD autoantigen and showed by Northern blot analysis that the BP180 and BP240 antigens are encoded by distinct RNA transcripts with lengths of 6.0 and 8.5 kb, respectively. They demonstrated by immunoelectron microscopy that, like the BP240 antigen, the BP180 antigen is located on the hemidesmosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1698819" 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="#19" class="mim-tip-reference" title="Li, K., Sawamura, D., Giudice, G. J., Diaz, L. A., Mattei, M.-G., Chu, M.-L., Uitto, J. <strong>Genomic organization of collagenous domains and chromosomal assignment of human 180-kDa bullous pemphigoid antigen-2, a novel collagen of stratified squamous epithelium.</strong> J. Biol. Chem. 266: 24064-24069, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1748679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1748679</a>]" pmid="1748679">Li et al. (1991)</a> found that the cDNA encoding BPAG2 predicts an amino acid sequence with 2 collagenous domains characterized by gly-X-Y repeats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1748679" 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="#30" class="mim-tip-reference" title="Sawamura, D., Li, K., Uitto, J. <strong>230-kD and 180-kD bullous pemphigoid antigens are distinct gene products. (Letter)</strong> J. Invest. Derm. 98: 942-943, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1497743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1497743</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12460914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1497743">Sawamura et al. (1992)</a> reviewed data unequivocally demonstrating that BPAG1 and BPAG2 (DST) are distinct gene products without structural homology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1497743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The work of <a href="#20" class="mim-tip-reference" title="Li, K., Tamai, K., Tan, E. M. L., Uitto, J. <strong>Cloning of type XVII collagen: complementary and genomic sequences of mouse 180-kDa bullous pemphigoid antigen (BPAG2) predict an interrupted collagenous domain, a transmembranous segment, and unusual features in the 5-prime end of the gene and the 3-prime-untranslated region of the mRNA.</strong> J. Biol. Chem. 268: 8825-8834, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8473327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8473327</a>]" pmid="8473327">Li et al. (1993)</a> indicated that the 180-kD bullous pemphigoid antigen is a transmembranous hemidesmosomal collagen designated type XVII collagen (COL17A1). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8473327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gatalica, B., Pulkkinen, L., Li, K., Kuokkanen, K., Ryynanen, M., McGrath, J. A., Uitto, J. <strong>Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 352-365, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9012408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9012408</a>]" pmid="9012408">Gatalica et al. (1997)</a> determined that the COL17A1 protein, which they called the alpha1(XVII) chain, consists of an intracellular globular domain, a transmembrane segment, and an extracellular domain that contains 15 separate collagenous subdomains, the largest consisting of 242 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9012408" 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="#31" class="mim-tip-reference" title="Schacke, H., Schumann, H., Hammami-Hauasli, N., Raghunath, M., Bruckner-Tuderman, L. <strong>Two forms of collagen XVII in keratinocytes. A full-length transmembrane protein and a soluble ectodomain.</strong> J. Biol. Chem. 273: 25937-25943, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9748270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9748270</a>] [<a href="https://doi.org/10.1074/jbc.273.40.25937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9748270">Schacke et al. (1998)</a> identified 2 molecular forms of collagen XVII in human skin and epithelial cells. Full-length collagen XVII appeared as a homotrimeric transmembrane molecule of three 180-kD alpha1(XVII) chains. A second, soluble form was recognized with antibodies to the ectodomain, but not the endodomain. The soluble form exhibited molecular properties of the collagen XVII ectodomain: a triple-helical, N-glycosylated molecule of three 120-kD polypeptides. Additional studies by <a href="#31" class="mim-tip-reference" title="Schacke, H., Schumann, H., Hammami-Hauasli, N., Raghunath, M., Bruckner-Tuderman, L. <strong>Two forms of collagen XVII in keratinocytes. A full-length transmembrane protein and a soluble ectodomain.</strong> J. Biol. Chem. 273: 25937-25943, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9748270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9748270</a>] [<a href="https://doi.org/10.1074/jbc.273.40.25937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9748270">Schacke et al. (1998)</a> suggested that both the 180- and 120-kD polypeptides were translated from the same mRNA and that the 120-kD polypeptide was generated posttranslationally. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9748270" 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>Using droplet digital PCR (ddPCR), <a href="#18" class="mim-tip-reference" title="Jonsson, F., Bystrom, B., Davidson, A. E., Backman, L. J., Kellgren, T. G., Tuft, S. J., Koskela, T., Ryden, P., Sandgren, O., Danielson, P., Hardcastle, A. J., Golovleva, I. <strong>Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).</strong> Hum. Mutat. 36: 463-473, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25676728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25676728</a>] [<a href="https://doi.org/10.1002/humu.22764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25676728">Jonsson et al. (2015)</a> quantified COL17A1 expression in 20 different human tissues, including corneal epithelial cells. The highest level of COL17A1 expression in noncorneal tissue was detected in placenta, followed by cervix, trachea, thymus, small intestine, and esophagus; COL17A1 was almost undetectable in heart, liver, and spleen. However, expression of COL17A1 was very high in corneal epithelial cells. Immunohistochemical analysis of healthy donor corneas showed the strongest COL17A1 staining in the epithelial basement membrane and in epithelial cells, with a lower level in stromal cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25676728" 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>By immunohistochemical analysis of fresh keratoconic cornea, <a href="#27" class="mim-tip-reference" title="Oliver, V. F., van Bysterveldt, K. A., Cadzow, M., Steger, B., Romano, V., Markie, D., Hewitt, A. W., Mackey, D. A., Willoughby, C. E., Sherwin, T., Crosier, P. S., McGhee, C. N., Vincent, A. L. <strong>A COL17A1 splice-altering mutation is prevalent in inherited recurrent corneal erosions.</strong> Ophthalmology 123: 709-722, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26786512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26786512</a>] [<a href="https://doi.org/10.1016/j.ophtha.2015.12.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26786512">Oliver et al. (2016)</a> demonstrated that COL17A1 is expressed in both corneal epithelial cells and the Bowman layer. Col17a1 staining in zebrafish samples suggested protein presence in the external surface membranes of cells in the superficial squamous layer. At 3 days postfertilization, Col17a1 was present throughout the 2-cell layer of the developing cornea, and in adult zebrafish it was was restricted to the external surface membrane of superficial epithelial cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26786512" 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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<div class="mim-changed mim-change"><p><a href="#19" class="mim-tip-reference" title="Li, K., Sawamura, D., Giudice, G. J., Diaz, L. A., Mattei, M.-G., Chu, M.-L., Uitto, J. <strong>Genomic organization of collagenous domains and chromosomal assignment of human 180-kDa bullous pemphigoid antigen-2, a novel collagen of stratified squamous epithelium.</strong> J. Biol. Chem. 266: 24064-24069, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1748679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1748679</a>]" pmid="1748679">Li et al. (1991)</a> determined that the COL17A1 gene spans approximately 12 kb of genomic DNA. The coding segment has 19 exons varying in size from 27 to 222 basepairs. The organization of these exons and the splice sites at the intron-exon junctions were clearly different from other fibrillar and nonfibrillar collagen genes previously described. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1748679" 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></div>
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<p><a href="#12" class="mim-tip-reference" title="Gatalica, B., Pulkkinen, L., Li, K., Kuokkanen, K., Ryynanen, M., McGrath, J. A., Uitto, J. <strong>Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 352-365, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9012408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9012408</a>]" pmid="9012408">Gatalica et al. (1997)</a> cloned the entire human COL17A1 gene and elucidated its intron/exon organization. They demonstrated that the gene comprises 56 distinct exons, which span approximately 52 kb of the genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9012408" 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 COL17A1 gene was mapped to chromosome 10q24.3 by in situ hybridization (<a href="#29" class="mim-tip-reference" title="Sawamura, D., Li, K., Nomura, K., Sugita, Y., Christiano, A. M., Uitto, J. <strong>Bullous pemphigoid antigen: cDNA cloning, cellular expression, and evidence for polymorphism of the human gene.</strong> J. Invest. Derm. 96: 908-915, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2045679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2045679</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12475433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2045679">Sawamura et al., 1991</a>; <a href="#19" class="mim-tip-reference" title="Li, K., Sawamura, D., Giudice, G. J., Diaz, L. A., Mattei, M.-G., Chu, M.-L., Uitto, J. <strong>Genomic organization of collagenous domains and chromosomal assignment of human 180-kDa bullous pemphigoid antigen-2, a novel collagen of stratified squamous epithelium.</strong> J. Biol. Chem. 266: 24064-24069, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1748679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1748679</a>]" pmid="1748679">Li et al., 1991</a>). <a href="#2" class="mim-tip-reference" title="Copeland, N. G., Gilbert, D. J., Li, K., Sawamura, D., Giudice, G. J., Chu, M.-L., Jenkins, N. A., Uitto, J. <strong>Chromosomal localization of mouse bullous pemphigoid antigens, BPAG1 and BPAG2: identification of a new region of homology between mouse and human chromosomes.</strong> Genomics 15: 180-181, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432531</a>] [<a href="https://doi.org/10.1006/geno.1993.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432531">Copeland et al. (1993)</a> demonstrated that the homologous murine gene is located on the distal end of chromosome 19 in a region of homology to human chromosome 10q. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1748679+8432531+2045679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#34" class="mim-tip-reference" title="Tasanen, K., Eble, J. A., Aumailley, M., Schumann, H., Baetge, J., Tu, H., Bruckner, P., Bruckner-Tuderman, L. <strong>Collagen XVII is destabilized by a glycine substitution mutation in the cell adhesion domain Col15.</strong> J. Biol. Chem. 275: 3093-3099, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10652291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10652291</a>] [<a href="https://doi.org/10.1074/jbc.275.5.3093" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10652291">Tasanen et al. (2000)</a> expressed the largest collagenous domain of collagen XVII, Col15, in a eukaryotic episomal expression system. The protein fragment was triple-helical when produced in cultures containing ascorbic acid. When the vitamin supply was limited, the 4-hydroxyproline content was reduced from 74 to 9%, which resulted in a drastic reduction of the stability of the triple helix. A mutation associated with epidermolysis bullosa also had a striking effect on thermal stability of the recombinant fragment, causing partial unfolding at 4 degrees C. The recombinant protein fragment promoted cell adhesion of epithelial and fibroblast cell lines with a beta-1 integrin (<a href="/entry/135630">135630</a>)-mediated mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10652291" 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="#11" class="mim-tip-reference" title="Franzke, C.-W., Tasanen, K., Schacke, H., Zhou, Z., Tryggvason, K., Mauch, C., Zigrino, P., Sunnarborg, S., Lee, D. C., Fahrenholz, F., Bruckner-Tuderman, L. <strong>Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs.</strong> EMBO J. 21: 5026-5035, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12356719[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdf532" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12356719">Franzke et al. (2002)</a> showed that COL17A1 was cleaved near the cell membrane of HaCaT human keratinocytes, and that almost the entire extracellular domain of COL17A1 was released into the culture medium. Shedding was enhanced by phorbol esters and IL1B (<a href="/entry/147720">147720</a>), and it was inhibited by chemical metalloprotease inhibitors and TIMP3 (<a href="/entry/188826">188826</a>), but not by TIMP2 (<a href="/entry/188825">188825</a>). RT-PCR showed that TACE (ADAM17; <a href="/entry/603639">603639</a>), ADAM10 (<a href="/entry/602192">602192</a>), and ADAM9 (<a href="/entry/602713">602713</a>), but not other metalloproteases, were expressed by HaCaT cells. HaCaT cells transfected with mouse Tace, human ADAM9, or bovine Adam10 showed increased COL17A1 shedding. Conversely, mouse keratinocytes deficient in Tace showed less Col17a1 shedding. In addition, HaCaT cells overexpressing Tace, ADAM9, or Adam10 showed reduced motility. <a href="#11" class="mim-tip-reference" title="Franzke, C.-W., Tasanen, K., Schacke, H., Zhou, Z., Tryggvason, K., Mauch, C., Zigrino, P., Sunnarborg, S., Lee, D. C., Fahrenholz, F., Bruckner-Tuderman, L. <strong>Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs.</strong> EMBO J. 21: 5026-5035, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12356719[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdf532" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12356719">Franzke et al. (2002)</a> also found that furin (<a href="/entry/136950">136950</a>) was likely involved in COL17A1 shedding and suggested that it may activate the metalloproteases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12356719" 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="#24" class="mim-tip-reference" title="Matsumura, H., Mohri, Y., Binh, N. T., Morinaga, H., Fukuda, M., Ito, M., Kurata, S., Hoeijmakers, J., Nishimura, E. K. <strong>Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis.</strong> Science 351: aad4395, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26912707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26912707</a>] [<a href="https://doi.org/10.1126/science.aad4395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26912707">Matsumura et al. (2016)</a> showed that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wildtype mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26912707" 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="#22" class="mim-tip-reference" title="Liu, N., Matsumura, H., Kato, T., Ichinose, S., Takada, A., Namiki, T., Asakawa, K., Morinaga, H., Mohri, Y., De Arcangelis, A., Geroges-Labouesse, E., Nanba, D., Nishimura, E. K. <strong>Stem cell competition orchestrates skin homeostasis and ageing.</strong> Nature 568: 344-350, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30944469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30944469</a>] [<a href="https://doi.org/10.1038/s41586-019-1085-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30944469">Liu et al. (2019)</a> reported that the expression of the hemidesmosome component COL17A1 by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modeling showed that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing aging. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin aging. Conversely, the forced maintenance of COL17A1 rescues skin organ aging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30944469" 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><strong><em>Intermediate Junctional Epidermolysis Bullosa 4</em></strong></p><p>
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In patients with intermediate junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) with a phenotype designated GABEB (generalized atrophic benign epidermolysis bullosa), characterized by universal alopecia and atrophy of the skin, <a href="#14" class="mim-tip-reference" title="Jonkman, M. F., de Jong, M. C. J. M., Heeres, K., Pas, H. H., van der Meer, J. B., Owaribe, K., Martinez de Velasco, A. M., Niessen, C. M., Sonnenberg, A. <strong>180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.</strong> J. Clin. Invest. 95: 1345-1352, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7883981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7883981</a>] [<a href="https://doi.org/10.1172/JCI117785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7883981">Jonkman et al. (1995)</a> found that the BP180 antigen is deficient and the BPAG2 mRNA is reduced, suggesting that the BPAG2 gene is the site of the mutation. This was established to be the case by <a href="#26" class="mim-tip-reference" title="McGrath, J. A., Gatalica, B., Christiano, A. M., Li, K., Owaribe, K., McMillan, J. R., Eady, R. A. J., Uitto, J. <strong>Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.</strong> Nature Genet. 11: 83-86, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550320</a>] [<a href="https://doi.org/10.1038/ng0995-83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550320">McGrath et al. (1995)</a>, who demonstrated a mutation in the BPAG2 gene in this disorder (<a href="#0001">113811.0001</a>). In a series of 18 patients with nonlethal junctional epidermolysis bullosa from unrelated families studied by <a href="#15" class="mim-tip-reference" title="Jonkman, M. F., De Jong, M. C. J. M., Heeres, K., Steijlen, P. M., Owaribe, K., Kuster, W., Meurer, M., Gedde-Dahl, T., Jr., Sonnenberg, A., Bruckner-Tuderman, L. <strong>Generalized atrophic benign epidermolysis bullosa: either 180-kd bullous pemphigoid antigen or laminin-5 deficiency.</strong> Arch. Derm. 132: 145-150, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8629821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8629821</a>] [<a href="https://doi.org/10.1001/archderm.132.2.145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8629821">Jonkman et al. (1996)</a>, 9 presented with the clinical characteristics of GABEB. From immunofluorescence studies with monoclonal antibodies to BP180 and laminin-5, they concluded that the defect was in BP180 in 8 patients and laminin-5 (<a href="/entry/150310">150310</a>) in 1. Both BP180 and laminin-5 antigens were normally expressed in the other 9 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8629821+7550320+7883981" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gatalica, B., Pulkkinen, L., Li, K., Kuokkanen, K., Ryynanen, M., McGrath, J. A., Uitto, J. <strong>Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 352-365, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9012408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9012408</a>]" pmid="9012408">Gatalica et al. (1997)</a> described novel mutations (<a href="#0003">113811.0003</a> and <a href="#0004">113811.0004</a>) in the COL17A1 gene in patients with GABEB. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9012408" 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 4 unrelated families with junctional epidermolysis bullosa of different phenotypes, <a href="#10" class="mim-tip-reference" title="Floeth, M., Fiedorowicz, J., Schacke, H., Hammami-Hauasli, N., Owaribe, K., Trueb, R. M., Bruckner-Tuderman, L. <strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong> J. Invest. Derm. 111: 528-533, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9740252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9740252</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9740252">Floeth et al. (1998)</a> identified novel homozygous and compound heterozygous COL17A1 mutations. Three patients had GABEB, with nonscarring blistering and varying degrees of alopecia. The fourth patient had the localisata variant of junctional epidermolysis bullosa, with predominantly acral blistering and normal hair. Patients 1 and 2 carried homozygous deletions, 520delAG (<a href="#0010">113811.0010</a>) and 2965delG (<a href="#0011">113811.0011</a>), respectively. Patient 3 was compound heterozygous for a missense and a deletion mutation (G539E and 2666delTT), and patient 4 was heterozygous for a previously known mutation, arg1226 to ter (R1226X; <a href="#0001">113811.0001</a>). The deletions led to premature termination codons and drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of the collagen in GABEB skin. The missense mutation G539E allowed synthesis of immunoreactive collagen XVII in keratinocytes, but prevented its secretion, thus causing lack of the protein in the skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9740252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Floeth, M., Bruckner-Tuderman, L. <strong>Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes.</strong> Am. J. Hum. Genet. 65: 1530-1537, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577906</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577906[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577906">Floeth and Bruckner-Tuderman (1999)</a> described a family with severe nonlethal junctional epidermolysis bullosa who had mutations in both the laminin-5, beta-3 subunit (LAMB3; <a href="/entry/150310">150310</a>), and COL17A1 genes. The index patient was compound heterozygous for the COL17A1 mutations L855X (<a href="#0012">113811.0012</a>) and R1226X (<a href="#0001">113811.0001</a>) and was heterozygous for the LAMB3 mutation R635X (<a href="/entry/150310#0001">150310.0001</a>). As a consequence, 2 functionally related proteins were affected. Absence of collagen XVII and attenuated laminin-5 expression resulted in rudimentary hemidesmosome structure and separation of the epidermis from the basement membrane, with severe skin blistering as the clinical manifestation. In contrast, single heterozygotes carrying either (1) one or the other of the COL17A1 null alleles or (2) a double heterozygote for a COL17A1 and a LAMB3 null allele did not have a pathologic skin phenotype. These observations indicated that the known allelic heterogeneity in junctional epidermolysis bullosa (JEB) is further complicated by interactions between unlinked mutations. They also demonstrated that identification of 1 mutation in 1 gene is not sufficient for determination of the genetic basis of JEB in a given family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577906" 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>Somatic Mosaic Reversion in JEB4</em></strong></p><p>
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Jonkman et al. (<a href="#14" class="mim-tip-reference" title="Jonkman, M. F., de Jong, M. C. J. M., Heeres, K., Pas, H. H., van der Meer, J. B., Owaribe, K., Martinez de Velasco, A. M., Niessen, C. M., Sonnenberg, A. <strong>180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.</strong> J. Clin. Invest. 95: 1345-1352, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7883981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7883981</a>] [<a href="https://doi.org/10.1172/JCI117785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7883981">1995</a>, <a href="#15" class="mim-tip-reference" title="Jonkman, M. F., De Jong, M. C. J. M., Heeres, K., Steijlen, P. M., Owaribe, K., Kuster, W., Meurer, M., Gedde-Dahl, T., Jr., Sonnenberg, A., Bruckner-Tuderman, L. <strong>Generalized atrophic benign epidermolysis bullosa: either 180-kd bullous pemphigoid antigen or laminin-5 deficiency.</strong> Arch. Derm. 132: 145-150, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8629821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8629821</a>] [<a href="https://doi.org/10.1001/archderm.132.2.145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8629821">1996</a>) observed a mosaic pattern of immunoreactive type XVII collagen in clusters of basal cells in patches of clinically unaffected skin in a Dutch GABEB (JEB4; <a href="/entry/619787">619787</a>) patient, in whom the remainder of the skin demonstrated characteristic blistering from mechanical trauma. <a href="#16" class="mim-tip-reference" title="Jonkman, M. F., Scheffer, H., Stulp, R., Pas, H. H., Nijenhuis, M., Heeres, K., Owaribe, K., Pulkkinen, L., Uitto, J. <strong>Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion.</strong> Cell 88: 543-551, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9038345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9038345</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81894-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9038345">Jonkman et al. (1997)</a> demonstrated that the mosaic phenotype in this compound heterozygote patient was caused by reversion of one of the mutations in the COL17A1 gene. They also demonstrated that the reverse mutation was the result of the nonreciprocal transfer of a part of 1 parental allele for the other by a mitotic gene conversion mechanism. The maternal allele, carrying a 1706delA mutation (<a href="#0005">113811.0005</a>), showed reversion of the mutation and loss of heterozygosity (LOH) along a tract of at least 381 bp in revertant keratinocytes derived from clinically unaffected skin patches. The paternal mutation, R1226X (<a href="#0001">113811.0001</a>), remained present in all cell samples. <a href="#16" class="mim-tip-reference" title="Jonkman, M. F., Scheffer, H., Stulp, R., Pas, H. H., Nijenhuis, M., Heeres, K., Owaribe, K., Pulkkinen, L., Uitto, J. <strong>Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion.</strong> Cell 88: 543-551, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9038345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9038345</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81894-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9038345">Jonkman et al. (1997)</a> stated that the natural gene therapy reported here has implications for the design of gene therapy, since reversion of the affected genotype to carrier genotype of approximately 50% of the basal keratinocytes appeared to be sufficient to normalize the function of the skin, as noted in clinically unaffected skin patches of the patient with this autosomal recessive disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8629821+9038345+7883981" 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 56-year-old Austrian woman with GABEB and revertant mosaicism, <a href="#5" class="mim-tip-reference" title="Darling, T. N., Yee, C., Bauer, J. W., Hintner, H., Yancey, K. B. <strong>Revertant mosaicism: partial correction of a germ-line mutation in COL17A1 by a frame-restoring mutation.</strong> J. Clin. Invest. 103: 1371-1377, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10330419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10330419</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10330419[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI4338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10330419">Darling et al. (1999)</a> demonstrated partial correction of a maternally inherited germline 2-bp deletion in COL17A1 (<a href="#0009">113811.0009</a>) by a frame-restoring mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10330419" 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="#17" class="mim-tip-reference" title="Jonkman, M. F. <strong>Revertant mosaicism in human genetic disorders.</strong> Am. J. Med. Genet. 85: 361-364, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10398261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10398261</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19990806)85:4<361::aid-ajmg11>3.0.co;2-e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10398261">Jonkman (1999)</a> provided a general discussion of revertant mosaicism in human genetic disorders. They listed 6 mendelian disorders in which this phenomenon had been observed. Gene conversion was thought to be the mechanism in 2 instances. The only true back mutation appeared to be that in the autosomal recessive adenosine deaminase (ADA)-deficient type of severe combined immunodeficiency (ADA-SCID; see <a href="/entry/102700#0026">102700.0026</a>). See also <a href="/entry/308380#0010">308380.0010</a> for a possible example of revertant mosaicism in X-linked SCID. <a href="#38" class="mim-tip-reference" title="Youssoufian, H. <strong>Natural gene therapy and the Darwinian legacy.</strong> Nature Genet. 13: 255-256, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673116</a>] [<a href="https://doi.org/10.1038/ng0796-255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673116">Youssoufian (1996)</a> referred to this as 'natural gene therapy.' <a href="#37" class="mim-tip-reference" title="Wahn, V., Stephan, V., Hirschhorn, R. <strong>Reverse mutations--spontaneous amelioration or cure of inherited disorders?</strong> Europ. J. Pediat. 157: 613-617, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9727841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9727841</a>] [<a href="https://doi.org/10.1007/s004310050896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9727841">Wahn et al. (1998)</a> discussed reverse mutations as providing spontaneous amelioration or cure of inherited disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10398261+8673116+9727841" 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="#28" class="mim-tip-reference" title="Pasmooij, A. M. G., Pas, H. H., Deviaene, F. C. L., Nijenhuis, M., Jonkman, M. F. <strong>Multiple correcting COL17A1 mutations in patients with revertant mosaicism of epidermolysis bullosa.</strong> Am. J. Hum. Genet. 77: 727-740, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16252234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16252234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16252234[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/497344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16252234">Pasmooij et al. (2005)</a> reported the occurrence of multiple corrections in 2 unrelated probands with revertant mosaicism of non-Herlitz junctional epidermolysis bullosa due to mutations in the COL17A1 gene. Immunofluorescence microscopy and laser dissection microscopy, followed by DNA and RNA analysis, were performed on skin biopsy specimens. In patient 1, a true back mutation was identified in a specimen from the arm, and a second-site mutation which compensated for the frameshift caused by the inherited insertion mutation was identified in the 3-prime splice site of exon 55 in a specimen from the middle finger. Patient 2 showed--besides 2 distinct gene conversion events in specimens from the arm and hand sites, both of which corrected the 1706delA mutation (<a href="#0005">113811.0005</a>)--a second-site mutation in an ankle specimen that prevented the premature ending of the protein by the primary nonsense mutation. Thus, both inherited mutations, paternal as well as maternal, reverted at least once by different reversion events in distinct cell clusters in the described patients. The occurrence of multiple correcting mutations within the same patient indicated that in vivo reversion is less unusual than was generally thought. In one patient, mosaic patterns of type XVII collagen-positive keratinocytes were present in clinically unaffected and affected skin. This suggested that reversion may be overlooked and may happen more often than expected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16252234" 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>Epithelial Recurrent Erosion Dystrophy</em></strong></p><p>
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In affected members of an extended Swedish pedigree segregating autosomal dominant epithelial recurrent erosion dystrophy (ERED; <a href="/entry/122400">122400</a>), <a href="#18" class="mim-tip-reference" title="Jonsson, F., Bystrom, B., Davidson, A. E., Backman, L. J., Kellgren, T. G., Tuft, S. J., Koskela, T., Ryden, P., Sandgren, O., Danielson, P., Hardcastle, A. J., Golovleva, I. <strong>Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).</strong> Hum. Mutat. 36: 463-473, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25676728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25676728</a>] [<a href="https://doi.org/10.1002/humu.22764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25676728">Jonsson et al. (2015)</a> identified a heterozygous missense mutation in the COL17A1 gene (T939I; <a href="#0015">113811.0015</a>). In a similarly affected 5-generation family, <a href="#18" class="mim-tip-reference" title="Jonsson, F., Bystrom, B., Davidson, A. E., Backman, L. J., Kellgren, T. G., Tuft, S. J., Koskela, T., Ryden, P., Sandgren, O., Danielson, P., Hardcastle, A. J., Golovleva, I. <strong>Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).</strong> Hum. Mutat. 36: 463-473, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25676728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25676728</a>] [<a href="https://doi.org/10.1002/humu.22764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25676728">Jonsson et al. (2015)</a> analyzed an apparently nonpathogenic (<a href="#33" class="mim-tip-reference" title="Sullivan, L. S., Zhao, X., Bowne, S. J., Xu, X., Daiger, S. P., Yee, S. B., Yee, R. W. <strong>Exclusion of the human collagen type XVII (COL17A1) gene as the cause of Thiel-Behnke corneal dystrophy (CDB2) on chromosome 10q23-q25.</strong> Curr. Eye Res. 27: 223-226, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14562173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14562173</a>] [<a href="https://doi.org/10.1076/ceyr.27.4.223.16595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14562173">Sullivan et al., 2003</a>) synonymous variant in COL17A1 (G1052G; <a href="#0016">113811.0016</a>) that segregated fully with disease, and discovered that it creates a cryptic splice donor site resulting in aberrant pre-RNA splicing. Noting that ocular findings, including corneal blistering and erosions, had been reported in 23% of patients with nonlethal junctional epidermolysis bullosa and in 32% of patients with recessive forms of dystrophic EB (<a href="#8" class="mim-tip-reference" title="Fine, J.-D., Johnson, L. B., Weiner, M., Stein, A., Cash, S., Deleoz, J., Devries, D. T., Suchindran, C. <strong>Eye involvement in inherited epidermolysis bullosa: experience of the National Epidermolysis Bullosa Registry.</strong> Am. J. Ophthal. 138: 254-262, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15289135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15289135</a>] [<a href="https://doi.org/10.1016/j.ajo.2004.03.034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15289135">Fine et al., 2004</a>), <a href="#18" class="mim-tip-reference" title="Jonsson, F., Bystrom, B., Davidson, A. E., Backman, L. J., Kellgren, T. G., Tuft, S. J., Koskela, T., Ryden, P., Sandgren, O., Danielson, P., Hardcastle, A. J., Golovleva, I. <strong>Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).</strong> Hum. Mutat. 36: 463-473, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25676728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25676728</a>] [<a href="https://doi.org/10.1002/humu.22764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25676728">Jonsson et al. (2015)</a> suggested that it might be important to examine the cornea in heterozygous COL17A1 mutation carriers in EB families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25676728+14562173+15289135" 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 individuals from 4 families with ERED, including 2 families from New Zealand, 1 from Tasmania, and 1 from the UK, <a href="#27" class="mim-tip-reference" title="Oliver, V. F., van Bysterveldt, K. A., Cadzow, M., Steger, B., Romano, V., Markie, D., Hewitt, A. W., Mackey, D. A., Willoughby, C. E., Sherwin, T., Crosier, P. S., McGhee, C. N., Vincent, A. L. <strong>A COL17A1 splice-altering mutation is prevalent in inherited recurrent corneal erosions.</strong> Ophthalmology 123: 709-722, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26786512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26786512</a>] [<a href="https://doi.org/10.1016/j.ophtha.2015.12.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26786512">Oliver et al. (2016)</a> identified heterozygosity for the synonymous G1052G mutation in COL17A1. Haplotype analysis was consistent with a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26786512" 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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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912769 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912769;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912769?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#26" class="mim-tip-reference" title="McGrath, J. A., Gatalica, B., Christiano, A. M., Li, K., Owaribe, K., McMillan, J. R., Eady, R. A. J., Uitto, J. <strong>Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.</strong> Nature Genet. 11: 83-86, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550320</a>] [<a href="https://doi.org/10.1038/ng0995-83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550320">McGrath et al. (1995)</a> reported a 14-year-old male with typical clinical features of non-Herlitz (intermediate) junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>); they described the phenotype as GABEB (generalized atrophic benign epidermolysis bullosa). The parents, who were not related, were clinically normal. The patient was found to be a compound heterozygote for a premature termination mutation of both alleles of the BPAG2 gene: a paternally inherited C-to-T transition at nucleotide 3781 of their clone that converted an arginine residue to a nonsense codon (R1226X), and a maternally inherited 1-bp insertion of G at nucleotide position 4150 (<a href="#0002">113811.0002</a>) that resulted in a frameshift and premature termination codon 50 nucleotides downstream from the site of insertion. The 2 mutations in BPAG2 were symbolized R1226X and 4150insG by the authors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550320" 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 9-year-old girl (patient 2) with JEB4, <a href="#32" class="mim-tip-reference" title="Schumann, H., Hammami-Hauasli, N., Pulkkinen, L., Mauviel, A., Kuster, W., Luthi, U., Owaribe, K., Uitto, J., Bruckner-Tuderman, L. <strong>Three novel homozygous point mutations and a new polymorphism in the COL17A1 gene: relation to biological and clinical phenotypes of junctional epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 1344-1353, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199555</a>] [<a href="https://doi.org/10.1086/515463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199555">Schumann et al. (1997)</a> identified homozygosity for the R1226X mutation in COL17A1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199555" 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 34-year-old male (patient 4) with the localisata variant of junctional epidermolysis bullosa (see <a href="/entry/619787">619787</a>), the offspring of healthy nonconsanguineous Polish parents, <a href="#10" class="mim-tip-reference" title="Floeth, M., Fiedorowicz, J., Schacke, H., Hammami-Hauasli, N., Owaribe, K., Trueb, R. M., Bruckner-Tuderman, L. <strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong> J. Invest. Derm. 111: 528-533, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9740252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9740252</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9740252">Floeth et al. (1998)</a> found heterozygosity for an R1226X mutation in the COL17A1 gene, resulting from a C-to-T transition at nucleotide 3781. The mutation was also found in the patient's unaffected father and sister, but not in the mother; <a href="#10" class="mim-tip-reference" title="Floeth, M., Fiedorowicz, J., Schacke, H., Hammami-Hauasli, N., Owaribe, K., Trueb, R. M., Bruckner-Tuderman, L. <strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong> J. Invest. Derm. 111: 528-533, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9740252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9740252</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9740252">Floeth et al. (1998)</a> stated that the patient was 'compound heterozygous.' The patient had nonscarring blistering since birth, initially generalized but later localized to the distal extremities. During the course of the disease, a slight hyperpigmentation of the skin and dystrophy of the toenails developed. No dental anomalies were observed, but the patient had a tendency to dental caries. The scalp and body hair were completely normal. <a href="#10" class="mim-tip-reference" title="Floeth, M., Fiedorowicz, J., Schacke, H., Hammami-Hauasli, N., Owaribe, K., Trueb, R. M., Bruckner-Tuderman, L. <strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong> J. Invest. Derm. 111: 528-533, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9740252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9740252</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9740252">Floeth et al. (1998)</a> noted that the same mutation had previously been reported in GABEB families from the U.K., Holland, and Germany (<a href="#26" class="mim-tip-reference" title="McGrath, J. A., Gatalica, B., Christiano, A. M., Li, K., Owaribe, K., McMillan, J. R., Eady, R. A. J., Uitto, J. <strong>Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.</strong> Nature Genet. 11: 83-86, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550320</a>] [<a href="https://doi.org/10.1038/ng0995-83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550320">McGrath et al., 1995</a>; <a href="#16" class="mim-tip-reference" title="Jonkman, M. F., Scheffer, H., Stulp, R., Pas, H. H., Nijenhuis, M., Heeres, K., Owaribe, K., Pulkkinen, L., Uitto, J. <strong>Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion.</strong> Cell 88: 543-551, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9038345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9038345</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81894-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9038345">Jonkman et al., 1997</a>; <a href="#32" class="mim-tip-reference" title="Schumann, H., Hammami-Hauasli, N., Pulkkinen, L., Mauviel, A., Kuster, W., Luthi, U., Owaribe, K., Uitto, J., Bruckner-Tuderman, L. <strong>Three novel homozygous point mutations and a new polymorphism in the COL17A1 gene: relation to biological and clinical phenotypes of junctional epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 1344-1353, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199555</a>] [<a href="https://doi.org/10.1086/515463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199555">Schumann et al., 1997</a>). R1226X may represent a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9740252+9199555+7550320+9038345" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Floeth, M., Bruckner-Tuderman, L. <strong>Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes.</strong> Am. J. Hum. Genet. 65: 1530-1537, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577906</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577906[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577906">Floeth and Bruckner-Tuderman (1999)</a> described a family with severe nonlethal junctional epidermolysis bullosa who had mutations in both the laminin-5, beta-3 subunit (LAMB3; <a href="/entry/150310">150310</a>), and COL17A1 genes. The index patient, a 2-year-old boy, was compound heterozygous for the COL17A1 mutations leu855 to ter (L855X; <a href="#0012">113811.0012</a>) and R1226X, and heterozygous for the LAMB3 mutation R635X (<a href="/entry/150310#0001">150310.0001</a>). As a consequence, 2 functionally related proteins were affected. Absence of collagen XVII and attenuated laminin-5 expression resulted in rudimentary hemidesmosome structure and separation of the epidermis from the basement membrane, with severe skin blistering as the clinical manifestation. In contrast, single heterozygotes carrying either (1) one or the other of the COL17A1 null alleles or (2) a double heterozygote for a COL17A1 and a LAMB3 null allele did not have a pathologic skin phenotype. These observations indicated that the known allelic heterogeneity in JEB is further complicated by interactions between unlinked mutations. They also demonstrated that identification of 1 mutation in 1 gene is not sufficient for determination of the genetic basis of JEB in a given family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577906" 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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<strong>.0002 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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<p>For discussion of the 1-bp insertion in the COL17A1 gene that was found in compound heterozygous state in a patient with the non-Herlitz form of junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) by <a href="#26" class="mim-tip-reference" title="McGrath, J. A., Gatalica, B., Christiano, A. M., Li, K., Owaribe, K., McMillan, J. R., Eady, R. A. J., Uitto, J. <strong>Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.</strong> Nature Genet. 11: 83-86, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550320</a>] [<a href="https://doi.org/10.1038/ng0995-83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550320">McGrath et al. (1995)</a>, see <a href="#0001">113811.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550320" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1564673127 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564673127;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1564673127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1564673127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Finnish family (family A) with non-Herlitz junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>), <a href="#12" class="mim-tip-reference" title="Gatalica, B., Pulkkinen, L., Li, K., Kuokkanen, K., Ryynanen, M., McGrath, J. A., Uitto, J. <strong>Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 352-365, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9012408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9012408</a>]" pmid="9012408">Gatalica et al. (1997)</a> found homozygosity for a 5-bp deletion, 2944del5, which resulted in frameshift and a premature termination of translation 45 nucleotides downstream of the deletion in exon 43. The proband showed negative immunofluorescence staining with an anti-type XVII collagen antibody. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9012408" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912770 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912770;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912770?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Finnish family (family B), <a href="#12" class="mim-tip-reference" title="Gatalica, B., Pulkkinen, L., Li, K., Kuokkanen, K., Ryynanen, M., McGrath, J. A., Uitto, J. <strong>Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 352-365, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9012408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9012408</a>]" pmid="9012408">Gatalica et al. (1997)</a> demonstrated that the proband with non-Herlitz type of junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) was a compound heterozygote, with one allele containing the 2944del5 mutation (<a href="#0003">113811.0003</a>) of COL17A1 and the other containing a nonsense mutation, Q1023X. The proband showed negative immunofluorescence staining with an anti-type XVII collagen antibody. The results attested to the functional importance of type XVII collagen as a transmembrane component of the hemidesmosomes at the dermal/epidermal junction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9012408" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs753898533 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs753898533;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs753898533?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs753898533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs753898533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with non-Herlitz junctional epidermolysis bullosa (JEB4; <a href="/entry/226650">226650</a>) who was a compound heterozygote with the R1226X mutation (<a href="#0001">113811.0001</a>) on the paternal chromosome, <a href="#16" class="mim-tip-reference" title="Jonkman, M. F., Scheffer, H., Stulp, R., Pas, H. H., Nijenhuis, M., Heeres, K., Owaribe, K., Pulkkinen, L., Uitto, J. <strong>Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion.</strong> Cell 88: 543-551, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9038345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9038345</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81894-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9038345">Jonkman et al. (1997)</a> identified a 1706delA mutation on the maternal chromosome. The patient showed patches of clinically unaffected skin, whereas the remainder of the skin demonstrated characteristic blistering from mechanical trauma. They showed that the mosaic phenotype was caused by reversion of one of the mutations, as a result of the nonreciprocal transfer of a part of 1 paternal allele for the other by a mechanism designated mitotic gene conversion. Revertant keratinocytes derived from clinically unaffected skin patches showed LOH along a tract of at least 381 bp. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9038345" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912771 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912771;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912771?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001781284 OR RCV002247369 OR RCV002279925 OR RCV004742230" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001781284, RCV002247369, RCV002279925, RCV004742230" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001781284...</a>
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<p>In a 53-year-old man (patient 3), the offspring of third-cousin parents, with intermediate junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) classified as the localisata variant, <a href="#32" class="mim-tip-reference" title="Schumann, H., Hammami-Hauasli, N., Pulkkinen, L., Mauviel, A., Kuster, W., Luthi, U., Owaribe, K., Uitto, J., Bruckner-Tuderman, L. <strong>Three novel homozygous point mutations and a new polymorphism in the COL17A1 gene: relation to biological and clinical phenotypes of junctional epidermolysis bullosa.</strong> Am. J. Hum. Genet. 60: 1344-1353, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199555</a>] [<a href="https://doi.org/10.1086/515463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199555">Schumann et al. (1997)</a> demonstrated homozygosity for an 4013G-A transition in exon 52 of the COL17A1 gene, resulting in an arg1303-to-gln (R1303Q) mutation. The patient had trauma-induced blistering of the skin since school age but developed an overall milder phenotype, with blistering predominantly of the distal extremities and, occasionally, of the oral mucosa. During the course of the disease, all nails were lost, and mild skin atrophy developed on the extremities. Electron microscopy showed slight structural alterations of the hemidesmosomes. His unaffected daughter was heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199555" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1478395810 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1478395810;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1478395810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1478395810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 28-year-old Italian female, the product of a consanguineous union, with non-Herlitz junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) <a href="#1" class="mim-tip-reference" title="Chavanas, S., Gache, Y., Tadini, G., Pulkkinen, L., Uitto, J., Ortonne, J. P., Meneguzzi, G. <strong>A homozygous in-frame deletion in the collagenous domain of bullous pemphigoid antigen BP180 (type XVII collagen) causes generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 109: 74-78, 1997. Note: Erratum: J. Invest. Derm. 109: 613 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9204958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9204958</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12276614" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9204958">Chavanas et al. (1997)</a> detected homozygosity for a 2441-2A-G transition in the acceptor site of intron 31 of the COL17A1 gene, resulting in in-frame exon skipping within the collagenous ectodomain of the protein. The consequent deletion of 9 amino acids in the mutant BP180 was predicted to alter the structure of the homotrimer and to exert a deleterious effect on stability of the protein that would account for the complete absence of immunoreactivity of the proband's skin to antibodies directed against BP180. Each of her clinically normal parents was heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9204958" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1589562891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1589562891;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1589562891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1589562891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 19-year-old Austrian patient with a history of generalized blistering since birth with diffuse scalp alopecia and pitted, discolored teeth (JEB4; <a href="/entry/619787">619787</a>), designated the GABEB phenotype, <a href="#6" class="mim-tip-reference" title="Darling, T. N., Yee, C., Koh, B., McGrath, J. A., Bauer, J. W., Uitto, J., Hintner, H., Yancey, K. B. <strong>Cycloheximide facilitates the identification of aberrant transcripts resulting from a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 110: 165-169, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9457913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9457913</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00103.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9457913">Darling et al. (1998)</a> found heterozygosity for a G-to-T transversion at the -1 position of exon 32 of the COL17A1 gene. His parents were unrelated and showed no features. The mutation was inherited from the mother; although no paternally inherited mutation was identified, the authors considered it clear that the proband had a second genetic lesion, either paternally inherited or de novo. This acceptor splice site mutation led to the formation of aberrant transcripts present at extremely low levels. Based on their recent finding that cycloheximide stabilized mutant COL17A1 transcripts in keratinocytes homozygous for a frameshift mutation, <a href="#6" class="mim-tip-reference" title="Darling, T. N., Yee, C., Koh, B., McGrath, J. A., Bauer, J. W., Uitto, J., Hintner, H., Yancey, K. B. <strong>Cycloheximide facilitates the identification of aberrant transcripts resulting from a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 110: 165-169, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9457913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9457913</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00103.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9457913">Darling et al. (1998)</a> studied the effects of a splice site mutation on splicing of COL17A1 transcripts, using RT-PCR of total RNA from keratinocytes incubated in the presence or absence of cycloheximide. Using this approach, an abnormally spliced transcript was identified that contained an extra 264 bases upstream from exon 32, resulting in a premature termination codon 27 bp downstream from the cryptic splice site. Three other splice variants, including 1 derived from the skipping of exon 32, were also identified. These results indicated the usefulness of cycloheximide treatment in evaluating the abnormal processing of mRNA due to splice site mutations. Aberrant splicing often generates a premature termination codon. Transcripts with premature termination codons can occur at low or undetectable levels due to nonsense-mediated mRNA decay. The levels of these transcripts can be increased by cycloheximide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9457913" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2134563935 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2134563935;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2134563935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2134563935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 4 affected individuals from a family with non-Herlitz junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) originally described by <a href="#13" class="mim-tip-reference" title="Hintner, H., Wolff, K. <strong>Generalized atrophic benign epidermolysis bullosa.</strong> Arch. Derm. 118: 375-384, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7092249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7092249</a>]" pmid="7092249">Hintner and Wolff (1982)</a>, <a href="#25" class="mim-tip-reference" title="McGrath, J. A., Darling, T., Gatalica, B., Pohla-Gubo, G., Hintner, H., Christiano, A. M., Yancey, K., Uitto, J. <strong>A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 106: 771-774, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8618019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8618019</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12345821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8618019">McGrath et al. (1996)</a> detected homozygosity for a 2-bp deletion in the COL17A1 gene, 4003delTC. The mutation resulted in frameshift and premature termination of the protein 86 bp downstream. The unaffected mother and 2 unaffected sibs were heterozygous for the mutation; the father was deceased. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7092249+8618019" 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 8 affected individuals from 5 Austrian families with non-Herlitz junctional epidermolysis bullosa <a href="#4" class="mim-tip-reference" title="Darling, T. N., McGrath, J. A., Yee, C., Gatalica, B., Hametner, R., Bauer, J. W., Pohla-Gubo, G., Christiano, A. M., Uitto, J., Hintner, H., Yancey, K. B. <strong>Premature termination codons are present on both alleles of the bullous pemphigoid antigen 2/type XVII collagen gene in five Austrian families with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 108: 463-468, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9077475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9077475</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12289718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9077475">Darling et al. (1997)</a> detected a 2-bp deletion in COL17A1, 4003delTC. Family A had been studied by <a href="#25" class="mim-tip-reference" title="McGrath, J. A., Darling, T., Gatalica, B., Pohla-Gubo, G., Hintner, H., Christiano, A. M., Yancey, K., Uitto, J. <strong>A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 106: 771-774, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8618019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8618019</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12345821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8618019">McGrath et al. (1996)</a>. Affected members of 3 of the families (A-C) were homozygous for the mutation, and in the other 2 families (D, E) were compound heterozygous. In family E, the father and his affected son were heterozygous for a G-to-T transversion at nucleotide 2512 resulting in substitution of a premature termination codon for glycine (G803X; <a href="#0017">113811.0017</a>), with the 4003delTC mutation occurring on the maternal allele of the affected son. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9077475+8618019" 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>By haplotype analysis using microsatellites located in the region near COL17A1, <a href="#3" class="mim-tip-reference" title="Darling, T. N., Koh, B. B., Bale, S. J., Compton, J. G., Bauer, J. W., Hintner, H., Yancey, K. B. <strong>A deletion mutation in COL17A1 in five Austrian families with generalized atrophic benign epidermolysis bullosa represents propagation of an ancestral allele.</strong> J. Invest. Derm. 110: 170-173, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9457914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9457914</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00101.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9457914">Darling et al. (1998)</a> showed that the 4003delTC mutation in the 5 Austrian families originally studied by <a href="#13" class="mim-tip-reference" title="Hintner, H., Wolff, K. <strong>Generalized atrophic benign epidermolysis bullosa.</strong> Arch. Derm. 118: 375-384, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7092249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7092249</a>]" pmid="7092249">Hintner and Wolff (1982)</a> and <a href="#25" class="mim-tip-reference" title="McGrath, J. A., Darling, T., Gatalica, B., Pohla-Gubo, G., Hintner, H., Christiano, A. M., Yancey, K., Uitto, J. <strong>A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 106: 771-774, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8618019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8618019</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12345821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8618019">McGrath et al. (1996)</a> was located on a single ancestral allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9457914+7092249+8618019" 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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<strong>.0010 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs773423028 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs773423028;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs773423028?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs773423028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs773423028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002255768 OR RCV002279944" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002255768, RCV002279944" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002255768...</a>
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<p>In a 75-year-old German man (patient 1) with intermediate junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) classified as GABEB, <a href="#10" class="mim-tip-reference" title="Floeth, M., Fiedorowicz, J., Schacke, H., Hammami-Hauasli, N., Owaribe, K., Trueb, R. M., Bruckner-Tuderman, L. <strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong> J. Invest. Derm. 111: 528-533, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9740252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9740252</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9740252">Floeth et al. (1998)</a> found homozygosity for a deletion mutation, 520delAG, in the COL17A1 gene. Although the patient had never had axillary or pubic hair, scalp hair remained normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9740252" 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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<strong>.0011 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2134581672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2134581672;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2134581672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2134581672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002279928" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002279928" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002279928</a>
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<p>In a 6-year-old Turkish girl (patient 2) with intermediate junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) classified as GABEB, <a href="#10" class="mim-tip-reference" title="Floeth, M., Fiedorowicz, J., Schacke, H., Hammami-Hauasli, N., Owaribe, K., Trueb, R. M., Bruckner-Tuderman, L. <strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong> J. Invest. Derm. 111: 528-533, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9740252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9740252</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9740252">Floeth et al. (1998)</a> found homozygosity for a deletion mutation, 2956delG, in the COL17A1 gene. The mutation led to a premature termination codon and to drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of collagen in GABEB skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9740252" 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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<strong>.0012 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912772 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912772;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002279929" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002279929" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002279929</a>
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<p>For discussion of the leu855-to-ter (L855X) mutation in the COL17A1 gene that was found in compound heterozygous state in a patient with severe nonlethal junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) by <a href="#9" class="mim-tip-reference" title="Floeth, M., Bruckner-Tuderman, L. <strong>Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes.</strong> Am. J. Hum. Genet. 65: 1530-1537, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577906</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577906[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577906">Floeth and Bruckner-Tuderman (1999)</a>, see <a href="#0001">113811.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577906" 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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<strong>.0013 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912773 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912773;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912773" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121912773" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002279930" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002279930" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002279930</a>
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<p><a href="#35" class="mim-tip-reference" title="Tasanen, K., Floeth, M., Schumann, H., Bruckner-Tuderman, L. <strong>Hemizygosity for a glycine substitution in collagen XVII: unfolding and degradation of the ectodomain.</strong> J. Invest. Derm. 115: 207-212, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10951237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10951237</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2000.00049.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10951237">Tasanen et al. (2000)</a> studied the stability of collagen XVII in a 13-year-old boy with intermediate junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) who was compound heterozygous for the novel gly633-to-asp (G633D) mutation and the novel nonsense mutation, arg145 to ter (R145X; <a href="#0014">113811.0014</a>). Collagen XVII mRNA was significantly reduced, indicating nonsense-mediated mRNA degradation and hemizygosity of the patient for the G633D substitution. The thermal stability of the G633D mutant eukaryotic recombinant Col15 domain of collagen XVII was reduced. The midpoint of the helix-to-coil transition, Tm, was 5 degrees C lower than that of wildtype recombinant Col15, indicating abnormal triple-helix folding and susceptibility to proteolysis. Immunoassays consistently demonstrated reduced amounts of the full-length collagen XVII and absence of the soluble ectodomain in keratinocyte cultures, and lack of the ectodomain from the junctional epidermolysis bullosa skin. These observations showed that the G633D mutation in collagen XVII causes abnormal folding and susceptibility to degradation, and thus perturbs the physiologic adhesive functions of collagen XVII in the skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10951237" 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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<strong>.0014 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001382545 OR RCV002279931" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001382545, RCV002279931" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001382545...</a>
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<p>For discussion of the arg145-to-ter (R145X) mutation in the COL17A gene that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa (JEB4; <a href="/entry/619787">619787</a>) by <a href="#35" class="mim-tip-reference" title="Tasanen, K., Floeth, M., Schumann, H., Bruckner-Tuderman, L. <strong>Hemizygosity for a glycine substitution in collagen XVII: unfolding and degradation of the ectodomain.</strong> J. Invest. Derm. 115: 207-212, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10951237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10951237</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2000.00049.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10951237">Tasanen et al. (2000)</a>, see <a href="#0013">113811.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10951237" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797045142 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797045142;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs797045142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs797045142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000190896 OR RCV003556236" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190896, RCV003556236" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190896...</a>
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<p>In 35 affected members of an extended Swedish pedigree with epithelial recurrent erosion dystrophy (ERED; <a href="/entry/122400">122400</a>), <a href="#18" class="mim-tip-reference" title="Jonsson, F., Bystrom, B., Davidson, A. E., Backman, L. J., Kellgren, T. G., Tuft, S. J., Koskela, T., Ryden, P., Sandgren, O., Danielson, P., Hardcastle, A. J., Golovleva, I. <strong>Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).</strong> Hum. Mutat. 36: 463-473, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25676728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25676728</a>] [<a href="https://doi.org/10.1002/humu.22764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25676728">Jonsson et al. (2015)</a> identified heterozygosity for a c.2816C-T transition (c.2816C-T, NM_000494.3) in the COL17A1 gene, resulting in a thr939-to-ile (T939I) substitution. The mutation was not found in 9 unaffected family members, in 139 ethnically matched controls, or in the Exome Sequencing Project database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25676728" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs760714959 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs760714959;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs760714959?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs760714959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs760714959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000190897 OR RCV003447515 OR RCV005089967" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190897, RCV003447515, RCV005089967" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190897...</a>
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<p>In a 5-generation family with epithelial recurrent erosion dystrophy (ERED; <a href="/entry/122400">122400</a>), originally studied by <a href="#23" class="mim-tip-reference" title="Lohse, E., Stock, E. L., Jones, J. C. R., Braude, L. S., O'Grady, R. B., Roth, S. I. <strong>Reis-Bucklers' corneal dystrophy: immunofluorescent and electron microscopic studies.</strong> Cornea 8: 200-209, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2663347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2663347</a>]" pmid="2663347">Lohse et al. (1989)</a>, <a href="#33" class="mim-tip-reference" title="Sullivan, L. S., Zhao, X., Bowne, S. J., Xu, X., Daiger, S. P., Yee, S. B., Yee, R. W. <strong>Exclusion of the human collagen type XVII (COL17A1) gene as the cause of Thiel-Behnke corneal dystrophy (CDB2) on chromosome 10q23-q25.</strong> Curr. Eye Res. 27: 223-226, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14562173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14562173</a>] [<a href="https://doi.org/10.1076/ceyr.27.4.223.16595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14562173">Sullivan et al. (2003)</a> detected a heterozygous c.3156C-T transition (c.3156C-T, NM_000494.3) in exon 46 of the COL17A1 gene, resulting in a synonymous gly1052-to-gly (G1052G) substitution that segregated fully with disease but was believed to be nonpathogenic. <a href="#18" class="mim-tip-reference" title="Jonsson, F., Bystrom, B., Davidson, A. E., Backman, L. J., Kellgren, T. G., Tuft, S. J., Koskela, T., Ryden, P., Sandgren, O., Danielson, P., Hardcastle, A. J., Golovleva, I. <strong>Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED).</strong> Hum. Mutat. 36: 463-473, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25676728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25676728</a>] [<a href="https://doi.org/10.1002/humu.22764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25676728">Jonsson et al. (2015)</a> performed splicing assays in transfected HEK293 cells and demonstrated generation of an aberrantly spliced product with the c.3156C-T mutant that was 54 bp smaller than wildtype. Direct sequencing of the aberrant product demonstrated that the c.3156C-T variant creates a cryptic splice donor site 54 nucleotides upstream of the genuine splice donor site, causing truncation of exon 46 spliced onto exon 47 and resulting in insertion of a single amino acid (Gly1052Ala) followed by in-frame deletion of 17 amino acids (Gly1053_1070del). In the large Swedish family with ERED originally reported by <a href="#23" class="mim-tip-reference" title="Lohse, E., Stock, E. L., Jones, J. C. R., Braude, L. S., O'Grady, R. B., Roth, S. I. <strong>Reis-Bucklers' corneal dystrophy: immunofluorescent and electron microscopic studies.</strong> Cornea 8: 200-209, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2663347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2663347</a>]" pmid="2663347">Lohse et al. (1989)</a> and now consisting of 6 generations, <a href="#21" class="mim-tip-reference" title="Lin, B. R., Le, D. J., Chen, Y., Wang, Q., Chung, D. D., Frausto, R. F., Croasdale, C., Yee, R. W., Hejtmancik, F. J., Aldave, A. J. <strong>Whole exome sequencing and segregation analysis confirms that a mutation in COL17A1 is the cause of epithelial recurrent erosion dystrophy in a large dominant pedigree previously mapped to chromosome 10q23-q24.</strong> PLoS One 11: e0157418, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27309958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27309958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27309958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0157418" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27309958">Lin et al. (2016)</a> performed whole-exome sequencing and confirmed that the c.3156C-T change segregated completely with disease in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27309958+2663347+25676728+14562173" 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 4 families with ERED, including a large 3-generation New Zealand family (06NZ-TRB1) previously studied by <a href="#36" class="mim-tip-reference" title="Vincent, A. L., Markie, D. M., De Karolyi, B., Wheeldon, C. E., Patel, D. V., Grupcheva, C. N., McGhee, C. N. J. <strong>Exclusion of known corneal dystrophy genes in an autosomal dominant pedigree of a unique anterior membrane corneal dystrophy.</strong> Molec. Vision 15: 1700-1708, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19710953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19710953</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19710953[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="19710953">Vincent et al. (2009)</a>, an unrelated 3-generation New Zealand family (15NZ-LED1), a large 4-generation Tasmanian family (CDTAS1), and a large 3-generation family from the UK (UKOGA), <a href="#27" class="mim-tip-reference" title="Oliver, V. F., van Bysterveldt, K. A., Cadzow, M., Steger, B., Romano, V., Markie, D., Hewitt, A. W., Mackey, D. A., Willoughby, C. E., Sherwin, T., Crosier, P. S., McGhee, C. N., Vincent, A. L. <strong>A COL17A1 splice-altering mutation is prevalent in inherited recurrent corneal erosions.</strong> Ophthalmology 123: 709-722, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26786512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26786512</a>] [<a href="https://doi.org/10.1016/j.ophtha.2015.12.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26786512">Oliver et al. (2016)</a> identified heterozygosity for the c.3156C-T transition in COL17A1. The mutation segregated fully with disease in each of the families and was found once in the ExAC database (allele frequency, 8.240 x 10(-6)). Haplotype analysis with flanking microsatellite markers showed segregation with affected individuals in all 4 families, consistent with a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19710953+26786512" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs752317971 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs752317971;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs752317971?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs752317971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs752317971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of a gly803-to-ter (G803X) mutation in the COL17A1 gene that was identified in compound heterozygous state in an individual with intermediate junctional epidermolysis bullosa-4 (JEB4; <a href="/entry/619787">619787</a>) by <a href="#4" class="mim-tip-reference" title="Darling, T. N., McGrath, J. A., Yee, C., Gatalica, B., Hametner, R., Bauer, J. W., Pohla-Gubo, G., Christiano, A. M., Uitto, J., Hintner, H., Yancey, K. B. <strong>Premature termination codons are present on both alleles of the bullous pemphigoid antigen 2/type XVII collagen gene in five Austrian families with generalized atrophic benign epidermolysis bullosa.</strong> J. Invest. Derm. 108: 463-468, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9077475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9077475</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12289718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9077475">Darling et al. (1997)</a>, see <a href="#0009">113811.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9077475" 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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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1006/geno.1993.1027" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1046/j.1523-1747.1998.00101.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/1523-1747.ep12289718" target="_blank">Full Text</a>]
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<a id="Darling1999" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1172/JCI4338" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1046/j.1523-1747.1998.00103.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI114812" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ajo.2004.03.034" target="_blank">Full Text</a>]
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<strong>Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577906</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577906[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/302672" target="_blank">Full Text</a>]
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<strong>Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.</strong>
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[<a href="https://doi.org/10.1046/j.1523-1747.1998.00325.x" target="_blank">Full Text</a>]
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<div class="">
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Franzke, C.-W., Tasanen, K., Schacke, H., Zhou, Z., Tryggvason, K., Mauch, C., Zigrino, P., Sunnarborg, S., Lee, D. C., Fahrenholz, F., Bruckner-Tuderman, L.
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[<a href="https://doi.org/10.1093/emboj/cdf532" target="_blank">Full Text</a>]
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<a id="Gatalica1997" class="mim-anchor"></a>
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<div class="">
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<strong>Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa.</strong>
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</p>
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<a id="13" class="mim-anchor"></a>
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<a id="Hintner1982" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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<a id="Jonkman1995" class="mim-anchor"></a>
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<strong>180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7883981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7883981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7883981" 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/10.1172/JCI117785" target="_blank">Full Text</a>]
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<a id="Jonkman1996" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1001/archderm.132.2.145" target="_blank">Full Text</a>]
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<a id="Jonkman1997" class="mim-anchor"></a>
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Sullivan, L. S., Zhao, X., Bowne, S. J., Xu, X., Daiger, S. P., Yee, S. B., Yee, R. W.
|
|
<strong>Exclusion of the human collagen type XVII (COL17A1) gene as the cause of Thiel-Behnke corneal dystrophy (CDB2) on chromosome 10q23-q25.</strong>
|
|
Curr. Eye Res. 27: 223-226, 2003.
|
|
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|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14562173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14562173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14562173" 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/10.1076/ceyr.27.4.223.16595" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="34" class="mim-anchor"></a>
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<a id="Tasanen2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Tasanen, K., Eble, J. A., Aumailley, M., Schumann, H., Baetge, J., Tu, H., Bruckner, P., Bruckner-Tuderman, L.
|
|
<strong>Collagen XVII is destabilized by a glycine substitution mutation in the cell adhesion domain Col15.</strong>
|
|
J. Biol. Chem. 275: 3093-3099, 2000.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10652291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10652291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10652291" 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/10.1074/jbc.275.5.3093" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="35" class="mim-anchor"></a>
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<a id="Tasanen2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tasanen, K., Floeth, M., Schumann, H., Bruckner-Tuderman, L.
|
|
<strong>Hemizygosity for a glycine substitution in collagen XVII: unfolding and degradation of the ectodomain.</strong>
|
|
J. Invest. Derm. 115: 207-212, 2000.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10951237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10951237</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10951237" 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.1523-1747.2000.00049.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="36" class="mim-anchor"></a>
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<a id="Vincent2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vincent, A. L., Markie, D. M., De Karolyi, B., Wheeldon, C. E., Patel, D. V., Grupcheva, C. N., McGhee, C. N. J.
|
|
<strong>Exclusion of known corneal dystrophy genes in an autosomal dominant pedigree of a unique anterior membrane corneal dystrophy.</strong>
|
|
Molec. Vision 15: 1700-1708, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19710953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19710953</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19710953[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19710953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="37" class="mim-anchor"></a>
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<a id="Wahn1998" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Wahn, V., Stephan, V., Hirschhorn, R.
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<strong>Reverse mutations--spontaneous amelioration or cure of inherited disorders?</strong>
|
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Europ. J. Pediat. 157: 613-617, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9727841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9727841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9727841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004310050896" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="38" class="mim-anchor"></a>
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<a id="Youssoufian1996" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Youssoufian, H.
|
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<strong>Natural gene therapy and the Darwinian legacy.</strong>
|
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Nature Genet. 13: 255-256, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673116" 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/ng0796-255" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/11/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 10/31/2017<br>Ada Hamosh - updated : 06/07/2017<br>Marla J. F. O'Neill - updated : 9/17/2015<br>Patricia A. Hartz - updated : 10/28/2008<br>Victor A. McKusick - updated : 10/12/2005<br>Victor A. McKusick - updated : 3/19/2002<br>Gary A. Bellus - updated : 4/3/2001<br>Joanna S. Amberger - updated : 2/5/2001<br>Ada Hamosh - updated : 2/11/2000<br>Victor A. McKusick - updated : 12/17/1999<br>Victor A. McKusick - updated : 10/21/1999<br>Victor A. McKusick - updated : 9/14/1999<br>Victor A. McKusick - updated : 8/31/1999<br>Victor A. McKusick - updated : 2/4/1999<br>Victor A. McKusick - updated : 4/15/1998<br>Victor A. McKusick - updated : 9/19/1997<br>Victor A. McKusick - updated : 6/17/1997<br>Victor A. McKusick - updated : 4/7/1997<br>Victor A. McKusick - updated : 2/17/1997
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Victor A. McKusick : 11/13/1990
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/17/2025
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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carol : 03/28/2023<br>alopez : 03/29/2022<br>alopez : 02/17/2021<br>alopez : 09/11/2019<br>carol : 11/03/2017<br>alopez : 06/07/2017<br>carol : 04/25/2017<br>carol : 06/23/2016<br>carol : 1/30/2016<br>alopez : 9/17/2015<br>carol : 5/21/2015<br>mcolton : 5/19/2015<br>terry : 3/15/2013<br>terry : 11/3/2010<br>mgross : 10/28/2008<br>ckniffin : 7/1/2008<br>carol : 10/25/2007<br>carol : 10/22/2007<br>alopez : 10/14/2005<br>terry : 10/12/2005<br>carol : 7/29/2005<br>mgross : 3/17/2004<br>alopez : 5/22/2003<br>alopez : 12/3/2002<br>terry : 3/19/2002<br>cwells : 4/11/2001<br>cwells : 4/3/2001<br>alopez : 2/5/2001<br>joanna : 2/5/2001<br>carol : 11/16/2000<br>alopez : 2/15/2000<br>terry : 2/11/2000<br>mgross : 12/27/1999<br>terry : 12/17/1999<br>carol : 10/21/1999<br>jlewis : 9/14/1999<br>terry : 8/31/1999<br>carol : 2/9/1999<br>carol : 2/7/1999<br>terry : 2/4/1999<br>terry : 5/29/1998<br>carol : 5/8/1998<br>terry : 4/15/1998<br>mark : 9/23/1997<br>terry : 9/19/1997<br>terry : 6/23/1997<br>terry : 6/17/1997<br>mark : 4/7/1997<br>terry : 4/2/1997<br>mark : 2/17/1997<br>terry : 2/10/1997<br>mark : 3/28/1996<br>terry : 3/21/1996<br>mark : 3/4/1996<br>mark : 2/20/1996<br>mark : 8/31/1995<br>carol : 2/11/1993<br>supermim : 3/16/1992<br>carol : 2/12/1992<br>carol : 2/4/1992<br>carol : 1/10/1992
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
|
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<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 113811
|
|
</span>
|
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</h3>
|
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</div>
|
|
|
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<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COLLAGEN, TYPE XVII, ALPHA-1; COL17A1
|
|
|
|
</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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<div >
|
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
BULLOUS PEMPHIGOID ANTIGEN 2; BPAG2<br />
|
|
BP180
|
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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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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: COL17A1</em></strong>
|
|
</span>
|
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</p>
|
|
</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 715908008;
|
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</span>
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</p>
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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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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 10q25.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 10:104,031,286-104,085,880 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</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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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
10q25.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Epidermolysis bullosa, junctional 4, intermediate
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619787
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epithelial recurrent erosion dystrophy
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
122400
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Collagen XVII, a type II transmembrane protein, is a component of hemidesmosomes, which mediate the adhesion of keratinocytes and other epithelial cells to the underlying basement membrane. Collagen XVII can also be proteolytically shed from the cell surface of keratinocytes to generate a soluble basement membrane collagen (Franzke et al., 2002). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
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<span class="mim-text-font">
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<p>Autoantibodies present in the sera of patients with bullous pemphigoid (BP) bind to the basement membrane zone. In addition to recognizing the 240-kD basement membrane protein (BP240, or DST; 113810), they recognize a 180-kD protein in about 50% of all BP sera and in most sera from patients with herpes gestationis. Diaz et al. (1990) isolated a cDNA for the 180-kD autoantigen and showed by Northern blot analysis that the BP180 and BP240 antigens are encoded by distinct RNA transcripts with lengths of 6.0 and 8.5 kb, respectively. They demonstrated by immunoelectron microscopy that, like the BP240 antigen, the BP180 antigen is located on the hemidesmosome. </p><p>Li et al. (1991) found that the cDNA encoding BPAG2 predicts an amino acid sequence with 2 collagenous domains characterized by gly-X-Y repeats. </p><p>Sawamura et al. (1992) reviewed data unequivocally demonstrating that BPAG1 and BPAG2 (DST) are distinct gene products without structural homology. </p><p>The work of Li et al. (1993) indicated that the 180-kD bullous pemphigoid antigen is a transmembranous hemidesmosomal collagen designated type XVII collagen (COL17A1). </p><p>Gatalica et al. (1997) determined that the COL17A1 protein, which they called the alpha1(XVII) chain, consists of an intracellular globular domain, a transmembrane segment, and an extracellular domain that contains 15 separate collagenous subdomains, the largest consisting of 242 amino acids. </p><p>Schacke et al. (1998) identified 2 molecular forms of collagen XVII in human skin and epithelial cells. Full-length collagen XVII appeared as a homotrimeric transmembrane molecule of three 180-kD alpha1(XVII) chains. A second, soluble form was recognized with antibodies to the ectodomain, but not the endodomain. The soluble form exhibited molecular properties of the collagen XVII ectodomain: a triple-helical, N-glycosylated molecule of three 120-kD polypeptides. Additional studies by Schacke et al. (1998) suggested that both the 180- and 120-kD polypeptides were translated from the same mRNA and that the 120-kD polypeptide was generated posttranslationally. </p><p>Using droplet digital PCR (ddPCR), Jonsson et al. (2015) quantified COL17A1 expression in 20 different human tissues, including corneal epithelial cells. The highest level of COL17A1 expression in noncorneal tissue was detected in placenta, followed by cervix, trachea, thymus, small intestine, and esophagus; COL17A1 was almost undetectable in heart, liver, and spleen. However, expression of COL17A1 was very high in corneal epithelial cells. Immunohistochemical analysis of healthy donor corneas showed the strongest COL17A1 staining in the epithelial basement membrane and in epithelial cells, with a lower level in stromal cells. </p><p>By immunohistochemical analysis of fresh keratoconic cornea, Oliver et al. (2016) demonstrated that COL17A1 is expressed in both corneal epithelial cells and the Bowman layer. Col17a1 staining in zebrafish samples suggested protein presence in the external surface membranes of cells in the superficial squamous layer. At 3 days postfertilization, Col17a1 was present throughout the 2-cell layer of the developing cornea, and in adult zebrafish it was was restricted to the external surface membrane of superficial epithelial cells. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Li et al. (1991) determined that the COL17A1 gene spans approximately 12 kb of genomic DNA. The coding segment has 19 exons varying in size from 27 to 222 basepairs. The organization of these exons and the splice sites at the intron-exon junctions were clearly different from other fibrillar and nonfibrillar collagen genes previously described. </p><p>Gatalica et al. (1997) cloned the entire human COL17A1 gene and elucidated its intron/exon organization. They demonstrated that the gene comprises 56 distinct exons, which span approximately 52 kb of the genome. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>The COL17A1 gene was mapped to chromosome 10q24.3 by in situ hybridization (Sawamura et al., 1991; Li et al., 1991). Copeland et al. (1993) demonstrated that the homologous murine gene is located on the distal end of chromosome 19 in a region of homology to human chromosome 10q. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Tasanen et al. (2000) expressed the largest collagenous domain of collagen XVII, Col15, in a eukaryotic episomal expression system. The protein fragment was triple-helical when produced in cultures containing ascorbic acid. When the vitamin supply was limited, the 4-hydroxyproline content was reduced from 74 to 9%, which resulted in a drastic reduction of the stability of the triple helix. A mutation associated with epidermolysis bullosa also had a striking effect on thermal stability of the recombinant fragment, causing partial unfolding at 4 degrees C. The recombinant protein fragment promoted cell adhesion of epithelial and fibroblast cell lines with a beta-1 integrin (135630)-mediated mechanism. </p><p>Franzke et al. (2002) showed that COL17A1 was cleaved near the cell membrane of HaCaT human keratinocytes, and that almost the entire extracellular domain of COL17A1 was released into the culture medium. Shedding was enhanced by phorbol esters and IL1B (147720), and it was inhibited by chemical metalloprotease inhibitors and TIMP3 (188826), but not by TIMP2 (188825). RT-PCR showed that TACE (ADAM17; 603639), ADAM10 (602192), and ADAM9 (602713), but not other metalloproteases, were expressed by HaCaT cells. HaCaT cells transfected with mouse Tace, human ADAM9, or bovine Adam10 showed increased COL17A1 shedding. Conversely, mouse keratinocytes deficient in Tace showed less Col17a1 shedding. In addition, HaCaT cells overexpressing Tace, ADAM9, or Adam10 showed reduced motility. Franzke et al. (2002) also found that furin (136950) was likely involved in COL17A1 shedding and suggested that it may activate the metalloproteases. </p><p>Matsumura et al. (2016) showed that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wildtype mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ. </p><p>Liu et al. (2019) reported that the expression of the hemidesmosome component COL17A1 by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modeling showed that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing aging. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin aging. Conversely, the forced maintenance of COL17A1 rescues skin organ aging. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Intermediate Junctional Epidermolysis Bullosa 4</em></strong></p><p>
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In patients with intermediate junctional epidermolysis bullosa (JEB4; 619787) with a phenotype designated GABEB (generalized atrophic benign epidermolysis bullosa), characterized by universal alopecia and atrophy of the skin, Jonkman et al. (1995) found that the BP180 antigen is deficient and the BPAG2 mRNA is reduced, suggesting that the BPAG2 gene is the site of the mutation. This was established to be the case by McGrath et al. (1995), who demonstrated a mutation in the BPAG2 gene in this disorder (113811.0001). In a series of 18 patients with nonlethal junctional epidermolysis bullosa from unrelated families studied by Jonkman et al. (1996), 9 presented with the clinical characteristics of GABEB. From immunofluorescence studies with monoclonal antibodies to BP180 and laminin-5, they concluded that the defect was in BP180 in 8 patients and laminin-5 (150310) in 1. Both BP180 and laminin-5 antigens were normally expressed in the other 9 patients. </p><p>Gatalica et al. (1997) described novel mutations (113811.0003 and 113811.0004) in the COL17A1 gene in patients with GABEB. </p><p>In 4 unrelated families with junctional epidermolysis bullosa of different phenotypes, Floeth et al. (1998) identified novel homozygous and compound heterozygous COL17A1 mutations. Three patients had GABEB, with nonscarring blistering and varying degrees of alopecia. The fourth patient had the localisata variant of junctional epidermolysis bullosa, with predominantly acral blistering and normal hair. Patients 1 and 2 carried homozygous deletions, 520delAG (113811.0010) and 2965delG (113811.0011), respectively. Patient 3 was compound heterozygous for a missense and a deletion mutation (G539E and 2666delTT), and patient 4 was heterozygous for a previously known mutation, arg1226 to ter (R1226X; 113811.0001). The deletions led to premature termination codons and drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of the collagen in GABEB skin. The missense mutation G539E allowed synthesis of immunoreactive collagen XVII in keratinocytes, but prevented its secretion, thus causing lack of the protein in the skin. </p><p>Floeth and Bruckner-Tuderman (1999) described a family with severe nonlethal junctional epidermolysis bullosa who had mutations in both the laminin-5, beta-3 subunit (LAMB3; 150310), and COL17A1 genes. The index patient was compound heterozygous for the COL17A1 mutations L855X (113811.0012) and R1226X (113811.0001) and was heterozygous for the LAMB3 mutation R635X (150310.0001). As a consequence, 2 functionally related proteins were affected. Absence of collagen XVII and attenuated laminin-5 expression resulted in rudimentary hemidesmosome structure and separation of the epidermis from the basement membrane, with severe skin blistering as the clinical manifestation. In contrast, single heterozygotes carrying either (1) one or the other of the COL17A1 null alleles or (2) a double heterozygote for a COL17A1 and a LAMB3 null allele did not have a pathologic skin phenotype. These observations indicated that the known allelic heterogeneity in junctional epidermolysis bullosa (JEB) is further complicated by interactions between unlinked mutations. They also demonstrated that identification of 1 mutation in 1 gene is not sufficient for determination of the genetic basis of JEB in a given family. </p><p><strong><em>Somatic Mosaic Reversion in JEB4</em></strong></p><p>
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Jonkman et al. (1995, 1996) observed a mosaic pattern of immunoreactive type XVII collagen in clusters of basal cells in patches of clinically unaffected skin in a Dutch GABEB (JEB4; 619787) patient, in whom the remainder of the skin demonstrated characteristic blistering from mechanical trauma. Jonkman et al. (1997) demonstrated that the mosaic phenotype in this compound heterozygote patient was caused by reversion of one of the mutations in the COL17A1 gene. They also demonstrated that the reverse mutation was the result of the nonreciprocal transfer of a part of 1 parental allele for the other by a mitotic gene conversion mechanism. The maternal allele, carrying a 1706delA mutation (113811.0005), showed reversion of the mutation and loss of heterozygosity (LOH) along a tract of at least 381 bp in revertant keratinocytes derived from clinically unaffected skin patches. The paternal mutation, R1226X (113811.0001), remained present in all cell samples. Jonkman et al. (1997) stated that the natural gene therapy reported here has implications for the design of gene therapy, since reversion of the affected genotype to carrier genotype of approximately 50% of the basal keratinocytes appeared to be sufficient to normalize the function of the skin, as noted in clinically unaffected skin patches of the patient with this autosomal recessive disorder. </p><p>In a 56-year-old Austrian woman with GABEB and revertant mosaicism, Darling et al. (1999) demonstrated partial correction of a maternally inherited germline 2-bp deletion in COL17A1 (113811.0009) by a frame-restoring mutation. </p><p>Jonkman (1999) provided a general discussion of revertant mosaicism in human genetic disorders. They listed 6 mendelian disorders in which this phenomenon had been observed. Gene conversion was thought to be the mechanism in 2 instances. The only true back mutation appeared to be that in the autosomal recessive adenosine deaminase (ADA)-deficient type of severe combined immunodeficiency (ADA-SCID; see 102700.0026). See also 308380.0010 for a possible example of revertant mosaicism in X-linked SCID. Youssoufian (1996) referred to this as 'natural gene therapy.' Wahn et al. (1998) discussed reverse mutations as providing spontaneous amelioration or cure of inherited disorders. </p><p>Pasmooij et al. (2005) reported the occurrence of multiple corrections in 2 unrelated probands with revertant mosaicism of non-Herlitz junctional epidermolysis bullosa due to mutations in the COL17A1 gene. Immunofluorescence microscopy and laser dissection microscopy, followed by DNA and RNA analysis, were performed on skin biopsy specimens. In patient 1, a true back mutation was identified in a specimen from the arm, and a second-site mutation which compensated for the frameshift caused by the inherited insertion mutation was identified in the 3-prime splice site of exon 55 in a specimen from the middle finger. Patient 2 showed--besides 2 distinct gene conversion events in specimens from the arm and hand sites, both of which corrected the 1706delA mutation (113811.0005)--a second-site mutation in an ankle specimen that prevented the premature ending of the protein by the primary nonsense mutation. Thus, both inherited mutations, paternal as well as maternal, reverted at least once by different reversion events in distinct cell clusters in the described patients. The occurrence of multiple correcting mutations within the same patient indicated that in vivo reversion is less unusual than was generally thought. In one patient, mosaic patterns of type XVII collagen-positive keratinocytes were present in clinically unaffected and affected skin. This suggested that reversion may be overlooked and may happen more often than expected. </p><p><strong><em>Epithelial Recurrent Erosion Dystrophy</em></strong></p><p>
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In affected members of an extended Swedish pedigree segregating autosomal dominant epithelial recurrent erosion dystrophy (ERED; 122400), Jonsson et al. (2015) identified a heterozygous missense mutation in the COL17A1 gene (T939I; 113811.0015). In a similarly affected 5-generation family, Jonsson et al. (2015) analyzed an apparently nonpathogenic (Sullivan et al., 2003) synonymous variant in COL17A1 (G1052G; 113811.0016) that segregated fully with disease, and discovered that it creates a cryptic splice donor site resulting in aberrant pre-RNA splicing. Noting that ocular findings, including corneal blistering and erosions, had been reported in 23% of patients with nonlethal junctional epidermolysis bullosa and in 32% of patients with recessive forms of dystrophic EB (Fine et al., 2004), Jonsson et al. (2015) suggested that it might be important to examine the cornea in heterozygous COL17A1 mutation carriers in EB families. </p><p>In affected individuals from 4 families with ERED, including 2 families from New Zealand, 1 from Tasmania, and 1 from the UK, Oliver et al. (2016) identified heterozygosity for the synonymous G1052G mutation in COL17A1. Haplotype analysis was consistent with a founder effect. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>17 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, ARG1226TER
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<br />
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SNP: rs121912769,
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gnomAD: rs121912769,
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ClinVar: RCV001352741, RCV001851939, RCV002279920
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>McGrath et al. (1995) reported a 14-year-old male with typical clinical features of non-Herlitz (intermediate) junctional epidermolysis bullosa (JEB4; 619787); they described the phenotype as GABEB (generalized atrophic benign epidermolysis bullosa). The parents, who were not related, were clinically normal. The patient was found to be a compound heterozygote for a premature termination mutation of both alleles of the BPAG2 gene: a paternally inherited C-to-T transition at nucleotide 3781 of their clone that converted an arginine residue to a nonsense codon (R1226X), and a maternally inherited 1-bp insertion of G at nucleotide position 4150 (113811.0002) that resulted in a frameshift and premature termination codon 50 nucleotides downstream from the site of insertion. The 2 mutations in BPAG2 were symbolized R1226X and 4150insG by the authors. </p><p>In a 9-year-old girl (patient 2) with JEB4, Schumann et al. (1997) identified homozygosity for the R1226X mutation in COL17A1. </p><p>In a 34-year-old male (patient 4) with the localisata variant of junctional epidermolysis bullosa (see 619787), the offspring of healthy nonconsanguineous Polish parents, Floeth et al. (1998) found heterozygosity for an R1226X mutation in the COL17A1 gene, resulting from a C-to-T transition at nucleotide 3781. The mutation was also found in the patient's unaffected father and sister, but not in the mother; Floeth et al. (1998) stated that the patient was 'compound heterozygous.' The patient had nonscarring blistering since birth, initially generalized but later localized to the distal extremities. During the course of the disease, a slight hyperpigmentation of the skin and dystrophy of the toenails developed. No dental anomalies were observed, but the patient had a tendency to dental caries. The scalp and body hair were completely normal. Floeth et al. (1998) noted that the same mutation had previously been reported in GABEB families from the U.K., Holland, and Germany (McGrath et al., 1995; Jonkman et al., 1997; Schumann et al., 1997). R1226X may represent a mutation hotspot. </p><p>Floeth and Bruckner-Tuderman (1999) described a family with severe nonlethal junctional epidermolysis bullosa who had mutations in both the laminin-5, beta-3 subunit (LAMB3; 150310), and COL17A1 genes. The index patient, a 2-year-old boy, was compound heterozygous for the COL17A1 mutations leu855 to ter (L855X; 113811.0012) and R1226X, and heterozygous for the LAMB3 mutation R635X (150310.0001). As a consequence, 2 functionally related proteins were affected. Absence of collagen XVII and attenuated laminin-5 expression resulted in rudimentary hemidesmosome structure and separation of the epidermis from the basement membrane, with severe skin blistering as the clinical manifestation. In contrast, single heterozygotes carrying either (1) one or the other of the COL17A1 null alleles or (2) a double heterozygote for a COL17A1 and a LAMB3 null allele did not have a pathologic skin phenotype. These observations indicated that the known allelic heterogeneity in JEB is further complicated by interactions between unlinked mutations. They also demonstrated that identification of 1 mutation in 1 gene is not sufficient for determination of the genetic basis of JEB in a given family. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, 1-BP INS, 4150G
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<br />
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ClinVar: RCV002279921
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 1-bp insertion in the COL17A1 gene that was found in compound heterozygous state in a patient with the non-Herlitz form of junctional epidermolysis bullosa (JEB4; 619787) by McGrath et al. (1995), see 113811.0001. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, 5-BP DEL, NT2944
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<br />
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SNP: rs1564673127,
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ClinVar: RCV002279922
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Finnish family (family A) with non-Herlitz junctional epidermolysis bullosa (JEB4; 619787), Gatalica et al. (1997) found homozygosity for a 5-bp deletion, 2944del5, which resulted in frameshift and a premature termination of translation 45 nucleotides downstream of the deletion in exon 43. The proband showed negative immunofluorescence staining with an anti-type XVII collagen antibody. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, GLN1023TER
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<br />
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SNP: rs121912770,
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gnomAD: rs121912770,
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ClinVar: RCV002279923
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Finnish family (family B), Gatalica et al. (1997) demonstrated that the proband with non-Herlitz type of junctional epidermolysis bullosa (JEB4; 619787) was a compound heterozygote, with one allele containing the 2944del5 mutation (113811.0003) of COL17A1 and the other containing a nonsense mutation, Q1023X. The proband showed negative immunofluorescence staining with an anti-type XVII collagen antibody. The results attested to the functional importance of type XVII collagen as a transmembrane component of the hemidesmosomes at the dermal/epidermal junction. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, 1-BP DEL, 1706A
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<br />
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SNP: rs753898533,
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gnomAD: rs753898533,
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ClinVar: RCV002279924
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with non-Herlitz junctional epidermolysis bullosa (JEB4; 226650) who was a compound heterozygote with the R1226X mutation (113811.0001) on the paternal chromosome, Jonkman et al. (1997) identified a 1706delA mutation on the maternal chromosome. The patient showed patches of clinically unaffected skin, whereas the remainder of the skin demonstrated characteristic blistering from mechanical trauma. They showed that the mosaic phenotype was caused by reversion of one of the mutations, as a result of the nonreciprocal transfer of a part of 1 paternal allele for the other by a mechanism designated mitotic gene conversion. Revertant keratinocytes derived from clinically unaffected skin patches showed LOH along a tract of at least 381 bp. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, ARG1303GLN
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<br />
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|
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SNP: rs121912771,
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gnomAD: rs121912771,
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ClinVar: RCV001781284, RCV002247369, RCV002279925, RCV004742230
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a 53-year-old man (patient 3), the offspring of third-cousin parents, with intermediate junctional epidermolysis bullosa (JEB4; 619787) classified as the localisata variant, Schumann et al. (1997) demonstrated homozygosity for an 4013G-A transition in exon 52 of the COL17A1 gene, resulting in an arg1303-to-gln (R1303Q) mutation. The patient had trauma-induced blistering of the skin since school age but developed an overall milder phenotype, with blistering predominantly of the distal extremities and, occasionally, of the oral mucosa. During the course of the disease, all nails were lost, and mild skin atrophy developed on the extremities. Electron microscopy showed slight structural alterations of the hemidesmosomes. His unaffected daughter was heterozygous for the mutation. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0007 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL17A1, IVS31AS, A-G, -2
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<br />
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|
SNP: rs1478395810,
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ClinVar: RCV000778270, RCV002279941
|
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|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a 28-year-old Italian female, the product of a consanguineous union, with non-Herlitz junctional epidermolysis bullosa (JEB4; 619787) Chavanas et al. (1997) detected homozygosity for a 2441-2A-G transition in the acceptor site of intron 31 of the COL17A1 gene, resulting in in-frame exon skipping within the collagenous ectodomain of the protein. The consequent deletion of 9 amino acids in the mutant BP180 was predicted to alter the structure of the homotrimer and to exert a deleterious effect on stability of the protein that would account for the complete absence of immunoreactivity of the proband's skin to antibodies directed against BP180. Each of her clinically normal parents was heterozygous for the mutation. </p>
|
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</span>
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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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<div>
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<h4>
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|
<span class="mim-font">
|
|
<strong>.0008 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
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|
COL17A1, IVS31AS, G-T, -1
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<br />
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|
|
SNP: rs1589562891,
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|
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ClinVar: RCV002279926
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|
|
|
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</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a 19-year-old Austrian patient with a history of generalized blistering since birth with diffuse scalp alopecia and pitted, discolored teeth (JEB4; 619787), designated the GABEB phenotype, Darling et al. (1998) found heterozygosity for a G-to-T transversion at the -1 position of exon 32 of the COL17A1 gene. His parents were unrelated and showed no features. The mutation was inherited from the mother; although no paternally inherited mutation was identified, the authors considered it clear that the proband had a second genetic lesion, either paternally inherited or de novo. This acceptor splice site mutation led to the formation of aberrant transcripts present at extremely low levels. Based on their recent finding that cycloheximide stabilized mutant COL17A1 transcripts in keratinocytes homozygous for a frameshift mutation, Darling et al. (1998) studied the effects of a splice site mutation on splicing of COL17A1 transcripts, using RT-PCR of total RNA from keratinocytes incubated in the presence or absence of cycloheximide. Using this approach, an abnormally spliced transcript was identified that contained an extra 264 bases upstream from exon 32, resulting in a premature termination codon 27 bp downstream from the cryptic splice site. Three other splice variants, including 1 derived from the skipping of exon 32, were also identified. These results indicated the usefulness of cycloheximide treatment in evaluating the abnormal processing of mRNA due to splice site mutations. Aberrant splicing often generates a premature termination codon. Transcripts with premature termination codons can occur at low or undetectable levels due to nonsense-mediated mRNA decay. The levels of these transcripts can be increased by cycloheximide. </p>
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</span>
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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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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
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COL17A1, 2-BP DEL, 4003TC
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<br />
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|
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SNP: rs2134563935,
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|
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ClinVar: RCV002279927
|
|
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|
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</span>
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</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected individuals from a family with non-Herlitz junctional epidermolysis bullosa (JEB4; 619787) originally described by Hintner and Wolff (1982), McGrath et al. (1996) detected homozygosity for a 2-bp deletion in the COL17A1 gene, 4003delTC. The mutation resulted in frameshift and premature termination of the protein 86 bp downstream. The unaffected mother and 2 unaffected sibs were heterozygous for the mutation; the father was deceased. </p><p>In 8 affected individuals from 5 Austrian families with non-Herlitz junctional epidermolysis bullosa Darling et al. (1997) detected a 2-bp deletion in COL17A1, 4003delTC. Family A had been studied by McGrath et al. (1996). Affected members of 3 of the families (A-C) were homozygous for the mutation, and in the other 2 families (D, E) were compound heterozygous. In family E, the father and his affected son were heterozygous for a G-to-T transversion at nucleotide 2512 resulting in substitution of a premature termination codon for glycine (G803X; 113811.0017), with the 4003delTC mutation occurring on the maternal allele of the affected son. </p><p>By haplotype analysis using microsatellites located in the region near COL17A1, Darling et al. (1998) showed that the 4003delTC mutation in the 5 Austrian families originally studied by Hintner and Wolff (1982) and McGrath et al. (1996) was located on a single ancestral allele. </p>
|
|
</span>
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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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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
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COL17A1, 2-BP DEL, 520AG
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<br />
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|
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SNP: rs773423028,
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|
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gnomAD: rs773423028,
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|
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|
|
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ClinVar: RCV002255768, RCV002279944
|
|
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|
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 75-year-old German man (patient 1) with intermediate junctional epidermolysis bullosa (JEB4; 619787) classified as GABEB, Floeth et al. (1998) found homozygosity for a deletion mutation, 520delAG, in the COL17A1 gene. Although the patient had never had axillary or pubic hair, scalp hair remained normal. </p>
|
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</span>
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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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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, 1-BP DEL, 2965G
|
|
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|
|
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<br />
|
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|
|
SNP: rs2134581672,
|
|
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|
|
|
|
ClinVar: RCV002279928
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Turkish girl (patient 2) with intermediate junctional epidermolysis bullosa (JEB4; 619787) classified as GABEB, Floeth et al. (1998) found homozygosity for a deletion mutation, 2956delG, in the COL17A1 gene. The mutation led to a premature termination codon and to drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of collagen in GABEB skin. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, LEU855TER
|
|
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|
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<br />
|
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|
|
SNP: rs121912772,
|
|
|
|
|
|
|
|
ClinVar: RCV002279929
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the leu855-to-ter (L855X) mutation in the COL17A1 gene that was found in compound heterozygous state in a patient with severe nonlethal junctional epidermolysis bullosa (JEB4; 619787) by Floeth and Bruckner-Tuderman (1999), see 113811.0001. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, GLY633ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912773,
|
|
|
|
|
|
|
|
ClinVar: RCV002279930
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Tasanen et al. (2000) studied the stability of collagen XVII in a 13-year-old boy with intermediate junctional epidermolysis bullosa (JEB4; 619787) who was compound heterozygous for the novel gly633-to-asp (G633D) mutation and the novel nonsense mutation, arg145 to ter (R145X; 113811.0014). Collagen XVII mRNA was significantly reduced, indicating nonsense-mediated mRNA degradation and hemizygosity of the patient for the G633D substitution. The thermal stability of the G633D mutant eukaryotic recombinant Col15 domain of collagen XVII was reduced. The midpoint of the helix-to-coil transition, Tm, was 5 degrees C lower than that of wildtype recombinant Col15, indicating abnormal triple-helix folding and susceptibility to proteolysis. Immunoassays consistently demonstrated reduced amounts of the full-length collagen XVII and absence of the soluble ectodomain in keratinocyte cultures, and lack of the ectodomain from the junctional epidermolysis bullosa skin. These observations showed that the G633D mutation in collagen XVII causes abnormal folding and susceptibility to degradation, and thus perturbs the physiologic adhesive functions of collagen XVII in the skin. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, ARG145TER
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121912774,
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|
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|
|
|
gnomAD: rs121912774,
|
|
|
|
|
|
ClinVar: RCV001382545, RCV002279931
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg145-to-ter (R145X) mutation in the COL17A gene that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa (JEB4; 619787) by Tasanen et al. (2000), see 113811.0013. </p>
|
|
</span>
|
|
</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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|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 EPITHELIAL RECURRENT EROSION DYSTROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, THR939ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797045142,
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|
|
|
|
|
|
|
ClinVar: RCV000190896, RCV003556236
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 35 affected members of an extended Swedish pedigree with epithelial recurrent erosion dystrophy (ERED; 122400), Jonsson et al. (2015) identified heterozygosity for a c.2816C-T transition (c.2816C-T, NM_000494.3) in the COL17A1 gene, resulting in a thr939-to-ile (T939I) substitution. The mutation was not found in 9 unaffected family members, in 139 ethnically matched controls, or in the Exome Sequencing Project database. </p>
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 EPITHELIAL RECURRENT EROSION DYSTROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, GLY1052GLY
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs760714959,
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|
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|
|
|
gnomAD: rs760714959,
|
|
|
|
|
|
ClinVar: RCV000190897, RCV003447515, RCV005089967
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-generation family with epithelial recurrent erosion dystrophy (ERED; 122400), originally studied by Lohse et al. (1989), Sullivan et al. (2003) detected a heterozygous c.3156C-T transition (c.3156C-T, NM_000494.3) in exon 46 of the COL17A1 gene, resulting in a synonymous gly1052-to-gly (G1052G) substitution that segregated fully with disease but was believed to be nonpathogenic. Jonsson et al. (2015) performed splicing assays in transfected HEK293 cells and demonstrated generation of an aberrantly spliced product with the c.3156C-T mutant that was 54 bp smaller than wildtype. Direct sequencing of the aberrant product demonstrated that the c.3156C-T variant creates a cryptic splice donor site 54 nucleotides upstream of the genuine splice donor site, causing truncation of exon 46 spliced onto exon 47 and resulting in insertion of a single amino acid (Gly1052Ala) followed by in-frame deletion of 17 amino acids (Gly1053_1070del). In the large Swedish family with ERED originally reported by Lohse et al. (1989) and now consisting of 6 generations, Lin et al. (2016) performed whole-exome sequencing and confirmed that the c.3156C-T change segregated completely with disease in the family. </p><p>In 4 families with ERED, including a large 3-generation New Zealand family (06NZ-TRB1) previously studied by Vincent et al. (2009), an unrelated 3-generation New Zealand family (15NZ-LED1), a large 4-generation Tasmanian family (CDTAS1), and a large 3-generation family from the UK (UKOGA), Oliver et al. (2016) identified heterozygosity for the c.3156C-T transition in COL17A1. The mutation segregated fully with disease in each of the families and was found once in the ExAC database (allele frequency, 8.240 x 10(-6)). Haplotype analysis with flanking microsatellite markers showed segregation with affected individuals in all 4 families, consistent with a founder effect. </p>
|
|
</span>
|
|
</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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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 4, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL17A1, GLY803TER
|
|
|
|
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<br />
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SNP: rs752317971,
|
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gnomAD: rs752317971,
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|
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ClinVar: RCV000376543, RCV000493431, RCV002279955
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of a gly803-to-ter (G803X) mutation in the COL17A1 gene that was identified in compound heterozygous state in an individual with intermediate junctional epidermolysis bullosa-4 (JEB4; 619787) by Darling et al. (1997), see 113811.0009. </p>
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</span>
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<strong>A homozygous in-frame deletion in the collagenous domain of bullous pemphigoid antigen BP180 (type XVII collagen) causes generalized atrophic benign epidermolysis bullosa.</strong>
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<strong>Premature termination codons are present on both alleles of the bullous pemphigoid antigen 2/type XVII collagen gene in five Austrian families with generalized atrophic benign epidermolysis bullosa.</strong>
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<strong>Cycloheximide facilitates the identification of aberrant transcripts resulting from a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa.</strong>
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Floeth, M., Bruckner-Tuderman, L.
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Franzke, C.-W., Tasanen, K., Schacke, H., Zhou, Z., Tryggvason, K., Mauch, C., Zigrino, P., Sunnarborg, S., Lee, D. C., Fahrenholz, F., Bruckner-Tuderman, L.
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<strong>Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs.</strong>
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Jonkman, M. F., de Jong, M. C. J. M., Heeres, K., Pas, H. H., van der Meer, J. B., Owaribe, K., Martinez de Velasco, A. M., Niessen, C. M., Sonnenberg, A.
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<strong>180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.</strong>
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J. Clin. Invest. 95: 1345-1352, 1995.
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Jonkman, M. F., De Jong, M. C. J. M., Heeres, K., Steijlen, P. M., Owaribe, K., Kuster, W., Meurer, M., Gedde-Dahl, T., Jr., Sonnenberg, A., Bruckner-Tuderman, L.
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<strong>Whole exome sequencing and segregation analysis confirms that a mutation in COL17A1 is the cause of epithelial recurrent erosion dystrophy in a large dominant pedigree previously mapped to chromosome 10q23-q24.</strong>
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Matsumura, H., Mohri, Y., Binh, N. T., Morinaga, H., Fukuda, M., Ito, M., Kurata, S., Hoeijmakers, J., Nishimura, E. K.
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<strong>Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis.</strong>
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<strong>A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa.</strong>
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<strong>Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.</strong>
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<strong>A COL17A1 splice-altering mutation is prevalent in inherited recurrent corneal erosions.</strong>
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Ophthalmology 123: 709-722, 2016.
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<p class="mim-text-font">
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Sawamura, D., Li, K., Uitto, J.
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<strong>230-kD and 180-kD bullous pemphigoid antigens are distinct gene products. (Letter)</strong>
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Schacke, H., Schumann, H., Hammami-Hauasli, N., Raghunath, M., Bruckner-Tuderman, L.
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Schumann, H., Hammami-Hauasli, N., Pulkkinen, L., Mauviel, A., Kuster, W., Luthi, U., Owaribe, K., Uitto, J., Bruckner-Tuderman, L.
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<strong>Three novel homozygous point mutations and a new polymorphism in the COL17A1 gene: relation to biological and clinical phenotypes of junctional epidermolysis bullosa.</strong>
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Sullivan, L. S., Zhao, X., Bowne, S. J., Xu, X., Daiger, S. P., Yee, S. B., Yee, R. W.
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<strong>Exclusion of the human collagen type XVII (COL17A1) gene as the cause of Thiel-Behnke corneal dystrophy (CDB2) on chromosome 10q23-q25.</strong>
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Tasanen, K., Eble, J. A., Aumailley, M., Schumann, H., Baetge, J., Tu, H., Bruckner, P., Bruckner-Tuderman, L.
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<strong>Collagen XVII is destabilized by a glycine substitution mutation in the cell adhesion domain Col15.</strong>
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Youssoufian, H.
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Ada Hamosh - updated : 09/11/2019<br>Marla J. F. O'Neill - updated : 10/31/2017<br>Ada Hamosh - updated : 06/07/2017<br>Marla J. F. O'Neill - updated : 9/17/2015<br>Patricia A. Hartz - updated : 10/28/2008<br>Victor A. McKusick - updated : 10/12/2005<br>Victor A. McKusick - updated : 3/19/2002<br>Gary A. Bellus - updated : 4/3/2001<br>Joanna S. Amberger - updated : 2/5/2001<br>Ada Hamosh - updated : 2/11/2000<br>Victor A. McKusick - updated : 12/17/1999<br>Victor A. McKusick - updated : 10/21/1999<br>Victor A. McKusick - updated : 9/14/1999<br>Victor A. McKusick - updated : 8/31/1999<br>Victor A. McKusick - updated : 2/4/1999<br>Victor A. McKusick - updated : 4/15/1998<br>Victor A. McKusick - updated : 9/19/1997<br>Victor A. McKusick - updated : 6/17/1997<br>Victor A. McKusick - updated : 4/7/1997<br>Victor A. McKusick - updated : 2/17/1997
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Victor A. McKusick : 11/13/1990
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