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Entry
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- *120215 - COLLAGEN, TYPE V, ALPHA-1; COL5A1
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- OMIM
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<p>
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<span class="h4">*120215</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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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="#cloning">Cloning and Expression</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="#geneStructure">Gene Structure</a>
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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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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/120215">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 role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div id="mimFloatingLinksMenu">
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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=ENSG00000130635;t=ENST00000371817" 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=1289" 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=120215" 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=ENSG00000130635;t=ENST00000371817" 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_000093,NM_001278074,XM_017014266" 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_000093" 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=120215" 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=00368&isoform_id=00368_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/COL5A1" 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/219510,1020326,38014150,62089314,85687376,89276751,119608534,119608535,119608536,119608537,119608538,190192196,444737795,495528154,583075130,583765368,1034663755,2462622609" 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/P20908" 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=1289" 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=ENSG00000130635;t=ENST00000371817" 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=COL5A1" 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=COL5A1" 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+1289" 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/COL5A1" 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:1289" 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/1289" 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=chr9&hgg_gene=ENST00000371817.8&hgg_start=134641803&hgg_end=134844843&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://search.clinicalgenome.org/kb/gene-dosage/HGNC:2209" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2209" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/col5a1" 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=120215[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=120215[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://www.deciphergenomics.org/gene/COL5A1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000130635" 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=COL5A1" 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=COL5A1" 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=COL5A1" 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="http://www.le.ac.uk/genetics/collagen/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=COL5A1&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/PA26724" 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:2209" 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:88457" 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/COL5A1#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:88457" 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/1289/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/OMIA002165/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1289" 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-041105-6" 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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:120215" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:1289" 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=COL5A1&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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</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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120215
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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 V, ALPHA-1; COL5A1
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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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<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=COL5A1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COL5A1</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/9/629?start=-3&limit=10&highlight=629">9q34.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:134641803-134844843&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'})">9:134,641,803-134,844,843</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>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=130000,619329" 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">
|
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<span class="mim-font">
|
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<a href="/geneMap/9/629?start=-3&limit=10&highlight=629">
|
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9q34.3
|
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Ehlers-Danlos syndrome, classic type, 1
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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/130000"> 130000 </a>
|
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Fibromuscular dysplasia, multifocal
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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/619329"> 619329 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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<p>Type V collagen was first identified in human placenta and adult skin, but later studies showed that it is present in many other tissues and organs as a minor collagen component. Type V collagen occurs as heterotrimers of 3 different polypeptide chains, alpha-1, alpha-2 (COL5A2; <a href="/entry/120190">120190</a>), and alpha-3 (COL5A3; <a href="/entry/120216">120216</a>), or 2 copies of alpha-1 and 1 copy of alpha-2; it also occurs as a homotrimer of alpha-1 polypeptides. <a href="#20" class="mim-tip-reference" title="Takahara, K., Sato, Y., Okazawa, K., Okamoto, N., Noda, A., Yaoi, Y., Kato, I. <strong>Complete primary structure of human collagen alpha-1(V) chain.</strong> J. Biol. Chem. 266: 13124-13129, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2071595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2071595</a>]" pmid="2071595">Takahara et al. (1991)</a> reported the sequence of cDNA encoding the complete prepro-alpha-1(V) chain. The collagenous region and COOH-terminal noncollagenous region closely resembled that of the alpha-1(XI) (<a href="/entry/120280">120280</a>) chain; however, codon usage differed, suggesting that the COL5A1 gene is evolutionarily distinct. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2071595" 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>Using cDNA and genomic clones for the COL5A1 gene as probes, <a href="#9" class="mim-tip-reference" title="Greenspan, D. S., Byers, M. G., Eddy, R. L., Cheng, W., Jani-Sait, S., Shows, T. B. <strong>Human collagen gene COL5A1 maps to the q34.2-q34.3 region of chromosome 9, near the locus for nail-patella syndrome.</strong> Genomics 12: 836-837, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1572660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1572660</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90320-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1572660">Greenspan et al. (1992)</a> determined in panels of human-mouse hybrid cell lines and by in situ hybridization experiments that the COL5A1 gene is located in the segment 9q34.2-q34.3. <a href="#5" class="mim-tip-reference" title="Caridi, G., Pezzolo, A., Bertelli, R., Gimelli, G., Di Donato, A., Candiano, G., Ghiggeri, G. M. <strong>Mapping of the human COL5A1 gene to chromosome 9q34.3.</strong> Hum. Genet. 90: 174-176, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1427773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1427773</a>] [<a href="https://doi.org/10.1007/BF00210769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1427773">Caridi et al. (1992)</a> likewise assigned the COL5A1 gene to 9q34.3 by in situ hybridization. <a href="#11" class="mim-tip-reference" title="Mattei, M. G., Bruce, B., Karsenty, G. <strong>Mouse alpha-1 type V collagen gene maps to the [A2-B] region of chromosome 2.</strong> Genomics 16: 786-788, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8325657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8325657</a>] [<a href="https://doi.org/10.1006/geno.1993.1270" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8325657">Mattei et al. (1993)</a> found that the homologous gene in the mouse is located in the A2-B region of chromosome 2. They independently confirmed the localization of the human gene to 9q34. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1427773+8325657+1572660" 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="#19" class="mim-tip-reference" title="Takahara, K., Hoffman, G. G., Greenspan, D. S. <strong>Complete structural organization of the human alpha-1(V) collagen gene (COL5A1): divergence from the conserved organization of other characterized fibrillar collagen genes.</strong> Genomics 29: 588-597, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575750</a>] [<a href="https://doi.org/10.1006/geno.1995.9961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575750">Takahara et al. (1995)</a> determined the complete genomic structure of COL5A1 and showed that the gene is more complex than other fibrillar collagen genes, having 66 exons compared to 52. The gene spans at least 750 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8575750" 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="#7" class="mim-tip-reference" title="Fichard, A., Kleman, J.-P., Ruggiero, F. <strong>Another look at collagen V and XI molecules.</strong> Matrix Biol. 14: 515-531, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8535602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8535602</a>] [<a href="https://doi.org/10.1016/s0945-053x(05)80001-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8535602">Fichard et al. (1995)</a> reviewed collagens V and XI and commented on their fundamental role in the control of fibrillogenesis, probably by forming a core within the fibrils. Another characteristic of these collagens is the partial retention of their N-propeptide extensions in tissue forms, which is unusual for known fibrillar collagens. The tissue locations of collagen V and XI are different, but their structural and biologic properties seem to be closely related. Their primary structures are highly conserved at both the gene and the protein level, and this conservation is the basis of their similar biologic properties. In particular, they are both resistant to mammalian collagenases, and surprisingly sensitive to trypsin. Although they have both cell adhesion and heparin binding sites that could be crucial in physiologic processes such as development and wound healing, the 2 collagens are usually buried within the major collagen fibrils. It had become evident that several collagen-type molecules are, in fact, heterotypic associations of chains from both collagens V and XI, demonstrating that these 2 collagens are not distinct types but a single type that can be called collagen V/XI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8535602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Baghdadi, M. B., Castel, D., Machado, L., Fukada, S., Birk, D. E., Relaix, F., Tajbakhsh, S., Mourikis, P. <strong>Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.</strong> Nature 557: 714-718, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795344</a>] [<a href="https://doi.org/10.1038/s41586-018-0144-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795344">Baghdadi et al. (2018)</a> showed that adult muscle satellite cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, <a href="#1" class="mim-tip-reference" title="Baghdadi, M. B., Castel, D., Machado, L., Fukada, S., Birk, D. E., Relaix, F., Tajbakhsh, S., Mourikis, P. <strong>Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.</strong> Nature 557: 714-718, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795344</a>] [<a href="https://doi.org/10.1038/s41586-018-0144-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795344">Baghdadi et al. (2018)</a> identified NOTCH1 (<a href="/entry/190198">190198</a>)/RBPJ (<a href="/entry/147183">147183</a>)-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, <a href="#1" class="mim-tip-reference" title="Baghdadi, M. B., Castel, D., Machado, L., Fukada, S., Birk, D. E., Relaix, F., Tajbakhsh, S., Mourikis, P. <strong>Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.</strong> Nature 557: 714-718, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795344</a>] [<a href="https://doi.org/10.1038/s41586-018-0144-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795344">Baghdadi et al. (2018)</a> showed that collagen V produced by satellite cells is a critical component of the quiescent niche, as depletion of collagen V by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of collagen V with satellite cells is mediated by the calcitonin receptor (CALCR; <a href="/entry/114131">114131</a>), for which collagen V acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in collagen V-null satellite cells. <a href="#1" class="mim-tip-reference" title="Baghdadi, M. B., Castel, D., Machado, L., Fukada, S., Birk, D. E., Relaix, F., Tajbakhsh, S., Mourikis, P. <strong>Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.</strong> Nature 557: 714-718, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795344</a>] [<a href="https://doi.org/10.1038/s41586-018-0144-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795344">Baghdadi et al. (2018)</a> concluded that their study revealed a Notch-COLV-calcitonin receptor signaling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29795344" 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>Ehlers-Danlos Syndrome, Classic Type 1</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Nicholls, A. C., McCarron, S., Narcisi, P., Pope, F. M. <strong>Molecular abnormalities of type V collagen in Ehlers Danlos syndrome. (Abstract)</strong> Am. J. Hum. Genet. 55 (suppl.): A233, 1994."None>Nicholls et al. (1994)</a> identified molecular abnormalities in type V collagen in 2 patients with Ehlers-Danlos syndrome. The first patient, with overlapping clinical features of both EDS I/II (EDSCL1; <a href="/entry/130000">130000</a>) and EDS VII (see <a href="/entry/130060">130060</a>) and additional unusual corneal abnormalities, was heterozygous for a G(+3)-to-T change in the 5-prime splice site leading to deletion of the upstream exon (<a href="#0001">120215.0001</a>). The in-frame 54-bp deletion eliminated 6 Gly-X-Y triplets from the triple helical domain. The second patient also showed clinical features of EDS I/II and had, in addition, vascular weakness similar to the EDS IV (<a href="/entry/130050">130050</a>) subtype. Both the alpha-1 and the alpha-2 chains of type V collagen ran with lower mobility than normal on SDS-page gels, indicative of excessive posttranslational modification of the protein due to a point mutation in 1 of the protein chains.</p><p>Using a polymorphic intragenic simple sequence repeat at the COL5A1 locus, <a href="#4" class="mim-tip-reference" title="Burrows, N. P., Nicholls, A. C., Yates, J. R. W., Gatward, G., Sarathachandra, P., Richards, A., Pope, F. M. <strong>The gene encoding collagen alpha-1(V) (COL5A1) is linked to mixed Ehlers-Danlos syndrome type I/II.</strong> J. Invest. Derm. 106: 1273-1276, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8752669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8752669</a>] [<a href="https://doi.org/10.1111/1523-1747.ep12348978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8752669">Burrows et al. (1996)</a> demonstrated tight linkage to EDS I/II in a 3-generation family, giving a lod score of 4.07 at zero recombination. The variation in expression in this family suggested that EDS types I and II are allelic, and the linkage data supported the hypothesis that mutation in COL5A1 can cause both phenotypes. That this was indeed the case was demonstrated by <a href="#13" class="mim-tip-reference" title="Nicholls, A. C., Oliver, J. E., McCarron, S., Harrison, J. B., Greenspan, D. S., Pope, F. M. <strong>An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome.</strong> J. Med. Genet. 33: 940-946, 1996. Note: Erratum: J. Med. Genet. 334: 87 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8950675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8950675</a>] [<a href="https://doi.org/10.1136/jmg.33.11.940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8950675">Nicholls et al. (1996)</a> who, in a patient with clinical features of Ehlers-Danlos syndrome type I/II and VII, demonstrated an exon-skipping mutation in the COL5A1 gene (<a href="#0001">120215.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8950675+8752669" 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="#23" class="mim-tip-reference" title="Wenstrup, R. J., Langland, G. T., Willing, M. C., D'Souza, V. N., Cole, W. G. <strong>A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-alpha-1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I).</strong> Hum. Molec. Genet. 5: 1733-1736, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923000</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1733" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923000">Wenstrup et al. (1996)</a> demonstrated that affected individuals in an EDS I COL5A1-linked family were heterozygous for a 4-bp deletion in intron 65 (<a href="#0002">120215.0002</a>). This deletion led to a 234-bp deletion of exon 65 in the processed mRNA for pro-alpha-1(V) collagen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I., Naeyaert, J.-M. <strong>Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II.</strong> Am. J. Hum. Genet. 60: 547-554, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042913</a>]" pmid="9042913">De Paepe et al. (1997)</a> likewise identified a mutation in COL5A1 segregating with EDS I in a 4-generation family (<a href="#0003">120215.0003</a>). In addition, they detected splicing defects in the COL5A1 gene in a patient with EDS I and in a family with EDS II (<a href="#0005">120215.0005</a>). Thus they proved that EDS I and II are allelic disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To determine whether allele-product instability could explain failure to identify some mutations in the COL5A1 gene in classic EDS, <a href="#16" class="mim-tip-reference" title="Schwarze, U., Atkinson, M., Hoffman, G. G., Greenspan, D. S., Byers, P. H. <strong>Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II).</strong> Am. J. Hum. Genet. 66: 1757-1765, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10796876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10796876</a>] [<a href="https://doi.org/10.1086/302933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10796876">Schwarze et al. (2000)</a> analyzed polymorphic variants in the COL5A1 gene in 16 individuals and examined mRNA for the expression of both alleles and for alterations in splicing. They found a splice site mutation in a single individual and determined that, in 6 individuals, the mRNA from one COL5A1 allele either was not expressed or was very unstable. They identified small insertions or deletions in 5 of these cell strains, but were unable to identify the mutation in the sixth individual. Thus, although as many as half of the mutations that give rise to EDS types I and II are likely to lie in the COL5A1 gene, a significant portion of them result in very low levels of mRNA from the mutant allele, as a consequence of nonsense-mediated mRNA decay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10796876" 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>Similarly, <a href="#22" class="mim-tip-reference" title="Wenstrup, R. J., Florer, J. B., Willing, M. C., Giunta, C., Steinmann, B., Young, F., Susic, M., Cole, W. G. <strong>COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS.</strong> Am. J. Hum. Genet. 66: 1766-1776, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777716</a>] [<a href="https://doi.org/10.1086/302930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10777716">Wenstrup et al. (2000)</a> found that 8 of 28 probands with classic EDS, who were heterozygous for expressed polymorphisms in COL5A1, showed complete or nearly complete loss of expression of one COL5A1 allele. Reduced levels of COL5A1 mRNA relative to levels of COL5A2 mRNA were also observed in the cultured fibroblasts from EDS probands. Products of the 2 COL5A1 alleles were approximately equal after the addition of cycloheximide to the fibroblast cultures. After harvesting of mRNAs from cycloheximide-treated cultured fibroblasts, heteroduplex analysis of overlapping RT-PCR segments spanning the complete COL5A1 cDNA showed anomalies in 4 of the 8 probands, leading to identification of causative mutations; in the remaining 4 probands, targeting of CGA-to-TGA mutations in genomic DNA revealed a premature stop codon in one of them. <a href="#22" class="mim-tip-reference" title="Wenstrup, R. J., Florer, J. B., Willing, M. C., Giunta, C., Steinmann, B., Young, F., Susic, M., Cole, W. G. <strong>COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS.</strong> Am. J. Hum. Genet. 66: 1766-1776, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777716</a>] [<a href="https://doi.org/10.1086/302930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10777716">Wenstrup et al. (2000)</a> estimated that one-third of persons with classic EDS have mutations of the COL5A1 gene that result in haploinsufficiency. These findings indicated that normal formation of the heterotypic collagen fibrils that contain types I, III, and V collagen require the expression of both COL5A1 alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777716" 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 42-year-old German man with EDS and spontaneous rupture of his left common iliac artery who was negative for mutation in COL3A1 (<a href="/entry/120180">120180</a>), <a href="#2" class="mim-tip-reference" title="Borck, G., Beighton, P., Wilhelm, C., Kohlhase, J., Kubisch, C. <strong>Arterial rupture in classic Ehlers-Danlos syndrome with COL5A1 mutation.</strong> Am. J. Med. Genet. 152A: 2090-2093, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20635400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20635400</a>] [<a href="https://doi.org/10.1002/ajmg.a.33541" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20635400">Borck et al. (2010)</a> identified a de novo heterozygous nonsense mutation (<a href="#0012">120215.0012</a>) in the COL5A1 gene. The authors stated that this was the first report of a patient with COL5A1 mutation-positive EDS and rupture of a large artery, suggesting that arterial rupture might be a rare complication of classic EDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20635400" 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="#18" class="mim-tip-reference" title="Symoens, S., Syx, D., Malfait, F., Callewaert, B., De Backer, J., Vanakker, O., Coucke, P., De Paepe, A. <strong>Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria.</strong> Hum. Mutat. 33: 1485-1493, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22696272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22696272</a>] [<a href="https://doi.org/10.1002/humu.22137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22696272">Symoens et al. (2012)</a> analyzed COL5A1 and COL5A2 in 126 patients with a diagnosis or suspicion of classic EDS. In 93 patients, a type V collagen defect was found, of which 73 were COL5A1 mutations, 13 were COL5A2 mutations, and 7 were COL5A1 null-alleles with mutation unknown. The majority of the 73 COL5A1 mutations generated a COL5A1 null-allele, whereas one-third were structural mutations, scattered throughout COL5A1. All COL5A2 mutations were structural mutations. Reduced availability of type V collagen appeared to be the major disease-causing mechanism, besides other intra- and extracellular contributing factors. All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring, and joint hypermobility. No COL5A1/COL5A2 mutation was detected in 24 patients who displayed skin and joint hyperextensibility but lacked dystrophic scarring. Overall, over 90% of patients fulfilling all major Villefranche criteria for classic EDS were shown to harbor a type V collagen defect, indicating that this is the major, if not the only, cause of classic EDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22696272" 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>Multifocal Fibromuscular Dysplasia</em></strong></p><p>
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In 4 unrelated patients with multifocal fibromuscular dysplasia (FMDMF; <a href="/entry/619329">619329</a>), <a href="#15" class="mim-tip-reference" title="Richer, J., Hill, H. L., Wang, Y., Yang, M.-L., Hunker, K. L., Lane, J., Blackburn, S., Coleman, D. M., Eliason, J., Sillon, G., D'Agostino, M.-D., Jetty, P., and 16 others. <strong>A novel recurrent COL5A1 genetic variant is associated with a dysplasia-associated arterial disease exhibiting dissections and fibromuscular dysplasia.</strong> Arterioscler. Thromb. Vasc. Biol. 40: 2686-2699, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32938213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32938213</a>] [<a href="https://doi.org/10.1161/ATVBAHA.119.313885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32938213">Richer et al. (2020)</a> identified heterozygosity for a missense mutation in the COL5A1 gene (G514S; <a href="#0013">120215.0013</a>). Ancestry analysis revealed a shared haplotype, suggesting a common founder. The mutation, which was not found in the gnomAD database, segregated with incomplete penetrance in the family of 1 of the probands. In a cohort of 264 unrelated adult patients with FMDMF, 134 of whom had dissections or macroaneurysms, the authors observed a higher burden of low-frequency COL5A1 variants, of unclear clinical significance but predicted to be deleterious, in patients who had experienced an arterial dissection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32938213" 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>Exclusion Studies</em></strong></p><p>
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<a href="#10" class="mim-tip-reference" title="Greenspan, D. S., Northrup, H., Au, K.-S., McAllister, K. A., Francomano, C. A., Wenstrup, R. J., Marchuk, D. A., Kwiatkowski, D. J. <strong>COL5A1: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II.</strong> Genomics 25: 737-739, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7759113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7759113</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80021-d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7759113">Greenspan et al. (1995)</a> used 3-prime untranslated region RFLPs to exclude the COL5A1 gene as a candidate in families with tuberous sclerosis-1 (<a href="/entry/191100">191100</a>), Ehlers-Danlos syndrome type II, and the nail-patella syndrome (<a href="/entry/161200">161200</a>). In addition, they described a polymorphic simple sequence repeat (SSR) within a COL5A1 intron. They used this SSR to exclude COL5A1 as a candidate gene also in hereditary hemorrhagic telangiectasia (<a href="/entry/187300">187300</a>), and to add COL5A1 to the index markers of chromosome 9 by evaluation of the COL5A1 locus on the CEPH 40-family reference pedigree set. This genetic mapping placed COL5A1 between markers D9S66 and D9S67. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7759113" 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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<strong>13 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=120215[MIM]" class="btn btn-default mim-tip-hint" role="button" 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>
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<strong>.0001 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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">rs786200922 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200922;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=rs786200922" 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=rs786200922" 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=RCV000018723 OR RCV000578847" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018723, RCV000578847" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018723...</a>
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<p><a href="#13" class="mim-tip-reference" title="Nicholls, A. C., Oliver, J. E., McCarron, S., Harrison, J. B., Greenspan, D. S., Pope, F. M. <strong>An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome.</strong> J. Med. Genet. 33: 940-946, 1996. Note: Erratum: J. Med. Genet. 334: 87 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8950675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8950675</a>] [<a href="https://doi.org/10.1136/jmg.33.11.940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8950675">Nicholls et al. (1996)</a> demonstrated a defect in COL5A1 in a 24-year-old woman with many features of the Ehlers-Danlos syndrome (EDSCL1; <a href="/entry/130000">130000</a>). She showed generalized skin fragility with extensive scarring of the forehead, shins, and knees, and scattered bruising on the arms and legs. She had marked generalized joint laxity with severe bilateral hallux valgus and diamond-shaped feet. She was short (155 cm), with mild thoracic kyphoscoliosis, pectus excavatum, and audible mitral valve prolapse. The eyes were unusually prominent and ophthalmologic examination demonstrated hypermetropia caused by flattened corneas. Because of the short stature and scoliosis, the differential diagnosis initially favored EDS VII (<a href="/entry/225410">225410</a>), but the cutaneous fragility and other features were also consistent with EDS types I and II. Electron microscopy of skin tissue indicated abnormal collagen fibrillogenesis with longitudinal sections showing a marked disruption of fibril packing, giving very irregular outlines to transverse sections. <a href="#13" class="mim-tip-reference" title="Nicholls, A. C., Oliver, J. E., McCarron, S., Harrison, J. B., Greenspan, D. S., Pope, F. M. <strong>An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome.</strong> J. Med. Genet. 33: 940-946, 1996. Note: Erratum: J. Med. Genet. 334: 87 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8950675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8950675</a>] [<a href="https://doi.org/10.1136/jmg.33.11.940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8950675">Nicholls et al. (1996)</a> analyzed the collagens produced by cultured fibroblasts and found that the type V collagen had a population of alpha-1(V) chains shorter than normal. Peptide mapping suggested a deletion within the triple helical domain. RT-PCR amplification of mRNA covering the whole of this domain of COL5A1 showed a deletion of 54 bp. <a href="#19" class="mim-tip-reference" title="Takahara, K., Hoffman, G. G., Greenspan, D. S. <strong>Complete structural organization of the human alpha-1(V) collagen gene (COL5A1): divergence from the conserved organization of other characterized fibrillar collagen genes.</strong> Genomics 29: 588-597, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575750</a>] [<a href="https://doi.org/10.1006/geno.1995.9961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575750">Takahara et al. (1995)</a> had reported that exon 49 is 54 bp long. <a href="#13" class="mim-tip-reference" title="Nicholls, A. C., Oliver, J. E., McCarron, S., Harrison, J. B., Greenspan, D. S., Pope, F. M. <strong>An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome.</strong> J. Med. Genet. 33: 940-946, 1996. Note: Erratum: J. Med. Genet. 334: 87 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8950675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8950675</a>] [<a href="https://doi.org/10.1136/jmg.33.11.940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8950675">Nicholls et al. (1996)</a> stated that although 6 Gly-X-Y triplets were lost from the domain, the essential triplet amino acid sequence and C-propeptide structure were maintained, allowing mutant protein chains to be incorporated into triple helices. Genomic DNA analysis identified a de novo G-to-T transversion at position +3 in a 5-prime splice site of one COL5A1 allele. The authors noted that similar mutations causing exon skipping in the major collagen genes, COL1A1 (<a href="/entry/120150">120150</a>), COL1A2 (<a href="/entry/120160">120160</a>), and COL3A1 (<a href="/entry/120180">120180</a>), have been identified in several cases of osteogenesis imperfecta and EDS type IV. These observations supported the hypothesis that type V, although quantitatively a minor collagen, has a critical role in the formation of fibrillar collagen matrix. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8950675+8575750" 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">rs786200923 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200923;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=rs786200923" 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=rs786200923" 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=RCV000018724" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018724" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018724</a>
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<p>In 2 families with EDS type I (EDSCL1; <a href="/entry/130000">130000</a>) linked to the COL5A1 gene, <a href="#23" class="mim-tip-reference" title="Wenstrup, R. J., Langland, G. T., Willing, M. C., D'Souza, V. N., Cole, W. G. <strong>A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-alpha-1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I).</strong> Hum. Molec. Genet. 5: 1733-1736, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923000</a>] [<a href="https://doi.org/10.1093/hmg/5.11.1733" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923000">Wenstrup et al. (1996)</a> reported a 4-bp deletion of nucleotides +3 to +6 in intron 65. The mutation caused a 234-bp deletion of exon 65 in the processed mRNA. They reported that this in-frame mutation predicts a pro-alpha-1(V) chain in which the C-propeptide is shortened by 78 amino acids. They noted that the deleted segment contains 2 of 8 highly conserved cysteine residues that are thought to participate in disulfhydryl bonds and facilitate chain association during molecular assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923000" 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>.0003 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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">rs80338764 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338764;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=rs80338764" 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=rs80338764" 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=RCV000032107 OR RCV001290029" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032107, RCV001290029" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032107...</a>
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<p><a href="#6" class="mim-tip-reference" title="De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I., Naeyaert, J.-M. <strong>Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II.</strong> Am. J. Hum. Genet. 60: 547-554, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042913</a>]" pmid="9042913">De Paepe et al. (1997)</a> identified a G-to-T transversion in the codon for cysteine-1181 (TGC) to the codon for serine (TCC). This represented a substitution of the most 5-prime cysteine residue within a highly conserved sequence of the C-propeptide domain of the pro-alpha-1(V) chain. The mutation thus caused reduction of collagen V by preventing incorporation of the mutant chains in the collagen V trimers. The patients were members of a family in which 7 individuals of 4 generations were affected with typical changes of type I EDS (EDSCL1; <a href="/entry/130000">130000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042913" 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">rs2132830442 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2132830442;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=rs2132830442" 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=rs2132830442" 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=RCV000018726" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018726" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018726</a>
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<p><a href="#6" class="mim-tip-reference" title="De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I., Naeyaert, J.-M. <strong>Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II.</strong> Am. J. Hum. Genet. 60: 547-554, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042913</a>]" pmid="9042913">De Paepe et al. (1997)</a> identified a de novo splicing mutation in a 13-year-old girl with classic features of EDS I (EDSCL1; <a href="/entry/130000">130000</a>). She was born prematurely after premature rupture of membranes with an umbilical hernia and bilateral dislocation of the hips. A deletion of exon 42 was demonstrated, resulting in the loss of approximately 100 bp. The mutation causing the deletion of exon 42 remained to be defined, as no sequence abnormalities in exon 42 or in the flanking 3-prime and 5-prime splice sites or the branch site were found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042913" 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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COL5A1, IVS64AS, T-A, -11
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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> rs183495554 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs183495554;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/rs183495554?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=rs183495554" 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=rs183495554" 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=RCV000018727" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018727" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018727</a>
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<p><a href="#6" class="mim-tip-reference" title="De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I., Naeyaert, J.-M. <strong>Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II.</strong> Am. J. Hum. Genet. 60: 547-554, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042913</a>]" pmid="9042913">De Paepe et al. (1997)</a> found a splicing mutation in the COL5A1 gene in a man in whom EDS type II (EDSCL1; <a href="/entry/130000">130000</a>) had been diagnosed at the age of 23 years because of a history of easy bruising and abnormal scarring and several luxations of the ankles while playing basketball. At age 32 years, he presented with moderate skin hyperextensibility and joint laxity and several pigmented paper scars on knees and shins. His 2 affected sons, aged 9 and 16 years, showed mild skin hyperextensibility, hyperlaxity of several joints, poor wound healing, and several ecchymoses and atrophic scars on the lower legs. A T-to-A transversion was found at position -11 of the 3-prime splice site of exon 65. The mutation caused abnormal splicing of the COL5A1 gene yielding 2 different mRNA products. One mRNA contained a 9-bp insertion because of the use of a new 3-prime splice site within IVS64. The second mRNA contained a deletion of 45 nucleotides at the 3-prime end of exon 65 because of the use of a cryptic splice site within exon 65. The mutation created a BsrI restriction site, which allowed <a href="#6" class="mim-tip-reference" title="De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I., Naeyaert, J.-M. <strong>Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II.</strong> Am. J. Hum. Genet. 60: 547-554, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042913</a>]" pmid="9042913">De Paepe et al. (1997)</a> to confirm the presence of the mutation in the affected sons and absence of the mutation in 30 control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042913" 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> rs765079080 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs765079080;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/rs765079080?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=rs765079080" 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=rs765079080" 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=RCV001290028" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001290028" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001290028</a>
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<p>Using an intragenic COL5A1 polymorphism, <a href="#3" class="mim-tip-reference" title="Burrows, N. P., Nicholls, A. C., Richards, A. J., Luccarini, C., Harrison, J. B., Yates, J. R. W., Pope, F. M. <strong>A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.</strong> Am. J. Hum. Genet. 63: 390-398, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683580</a>] [<a href="https://doi.org/10.1086/301948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683580">Burrows et al. (1998)</a> demonstrated linkage, at zero recombination, to the same allele in 2 large British EDS type II (EDSCL1; <a href="/entry/130000">130000</a>) families (lod scores 4.1 and 4.3). Affected members of each family were heterozygous for a point mutation in intron 32, causing the 45-bp exon 33 to be lost from the mRNA in approximately 60% of transcripts from the mutant gene. This mutation lies only 2 bp upstream of a highly conserved adenosine in the consensus branch-site sequence, which is required for lariat formation. Although both families shared the same marker allele, <a href="#3" class="mim-tip-reference" title="Burrows, N. P., Nicholls, A. C., Richards, A. J., Luccarini, C., Harrison, J. B., Yates, J. R. W., Pope, F. M. <strong>A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.</strong> Am. J. Hum. Genet. 63: 390-398, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683580</a>] [<a href="https://doi.org/10.1086/301948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683580">Burrows et al. (1998)</a> were unable to identify a common genealogy. This was the first description of a mutation at the lariat branch site, which plays a pivotal role in the splicing mechanism, in a collagen gene. (Mutations at the lariat branch site have been identified in the LCAT (<a href="/entry/606967">606967</a>), L1CAM (<a href="/entry/308840">308840</a>), and FBN2 (<a href="/entry/612570">612570</a>) genes.) <a href="#3" class="mim-tip-reference" title="Burrows, N. P., Nicholls, A. C., Richards, A. J., Luccarini, C., Harrison, J. B., Yates, J. R. W., Pope, F. M. <strong>A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.</strong> Am. J. Hum. Genet. 63: 390-398, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683580</a>] [<a href="https://doi.org/10.1086/301948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683580">Burrows et al. (1998)</a> suggested that the in-frame exon skipping produced by the mutation had a dominant-negative effect due to incorporation of the mutant pro-alpha chain into the triple-helical molecule. The mutation in this case was a T-to-G transversion at position -25 in intron 32. <a href="#3" class="mim-tip-reference" title="Burrows, N. P., Nicholls, A. C., Richards, A. J., Luccarini, C., Harrison, J. B., Yates, J. R. W., Pope, F. M. <strong>A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.</strong> Am. J. Hum. Genet. 63: 390-398, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683580</a>] [<a href="https://doi.org/10.1086/301948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683580">Burrows et al. (1998)</a> examined 11 affected members of one family and 8 affected members of the second. All fulfilled the clinical criteria for EDS type II (<a href="/entry/130000">130000</a>), namely, atrophic scarring confined to elbows and knees, evidence or history of easy bruising, joint laxity, and moderate cutaneous hyperextensibility. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683580" 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">rs121912932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912932;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=rs121912932" 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=rs121912932" 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="#8" class="mim-tip-reference" title="Giunta, C., Steinmann, B. <strong>Compound heterozygosity for a disease-causing G1489E and disease-modifying G530S substitution in COL5A1 of a patient with the classical type of Ehlers-Danlos syndrome: an explanation of intrafamilial variability?</strong> Am. J. Med. Genet. 90: 72-79, 2000. Note: Erratum: Am. J. Med. Genet. 93: 342 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10602121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10602121</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000103)90:1<72::aid-ajmg13>3.0.co;2-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10602121">Giunta and Steinmann (2000)</a> observed compound heterozygosity for a gly1489-to-glu (G1489E) mutation and a gly530-to-ser (G530S) mutation. (The former mutation was originally published as G1489D; a correction was published as a letter (<a href="#17" class="mim-tip-reference" title="Steinmann, B., Giunta, C. <strong>The devil of the one letter code and the Ehlers-Danlos syndrome: corrigendum. (Letter)</strong> Am. J. Med. Genet. 93: 342 only, 2000. Note: Erratum for Am. J. Med. Genet. 90: 72-79, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10946364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10946364</a>] [<a href="https://doi.org/10.1002/1096-8628(20000814)93:4<342::aid-ajmg16>3.0.co;2-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10946364">Steinmann and Giunta, 2000</a>).) The former mutation represented the first report of a glycine substitution in the main triple-helical region of COL5A1. The latter mutation was located in the NH2-terminal domain. The compound heterozygous father, the proband, had typical type I EDS (EDSCL1; <a href="/entry/130000">130000</a>). He had presented with microcornea at the age of 35 years at which time the skin was hyperelastic with numerous atrophic and hemosiderotic scars on the forehead, elbows, and legs, as well as molluscoid pseudotumors on the elbows, knees, heels, and toes. At the age of 57 years, he presented with secondary cutis laxa (e.g., of the eyelids), gross varicosities of the legs, and bladder diverticula leading to recurrent urinary tract infections. He had 2 daughters. The one daughter who inherited the G1489E mutation had milder expression of EDS. She was born 4 weeks before term because of premature rupture of the membranes. Muscular hypotonia was marked, necessitating feeding by a nasogastric tube, and was associated with a delay in gross motor development. At age 6, her skin was velvety, hyperelastic, and fragile, with atrophic and hemosiderotic scars on forehead, chin, and shins, and molluscoid pseudotumors on the elbows. There was marked joint hypermobility, and she had microcorneas. At age 20, she was clearly less severely affected than her father, with few abnormal scars, fewer molluscoid pseudotumors, and lesser skin hyperelasticity. The other daughter, who inherited the G530S mutation, and the proband's mother, from whom he had inherited the G530S mutation, presented with thin and smooth skin and delayed wound healing; the skin was not hyperelastic and did not present abnormal scars. The proband's father, from whom he presumably inherited the G1489E mutation, died at age 54 years of renal failure due to reflux nephropathy thought to be related to EDS. <a href="#8" class="mim-tip-reference" title="Giunta, C., Steinmann, B. <strong>Compound heterozygosity for a disease-causing G1489E and disease-modifying G530S substitution in COL5A1 of a patient with the classical type of Ehlers-Danlos syndrome: an explanation of intrafamilial variability?</strong> Am. J. Med. Genet. 90: 72-79, 2000. Note: Erratum: Am. J. Med. Genet. 93: 342 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10602121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10602121</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000103)90:1<72::aid-ajmg13>3.0.co;2-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10602121">Giunta and Steinmann (2000)</a> found the G530S substitution in 1 of 51 control individuals. This person was a healthy man without obvious connective tissue disorder; however, he had soft and hyperelastic skin without abnormal scars. His joints were not hypermobile. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10946364+10602121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Giunta, C., Steinmann, B. <strong>Compound heterozygosity for a disease-causing G1489E and disease-modifying G530S substitution in COL5A1 of a patient with the classical type of Ehlers-Danlos syndrome: an explanation of intrafamilial variability?</strong> Am. J. Med. Genet. 90: 72-79, 2000. Note: Erratum: Am. J. Med. Genet. 93: 342 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10602121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10602121</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000103)90:1<72::aid-ajmg13>3.0.co;2-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10602121">Giunta and Steinmann (2000)</a> pointed out that the NH2-terminal domain plays a crucial role in modulating fibril formation; hence, the G530S substitution may alter the structure and function of this region and consequently the formation of collagen fibrils. The combination of mutations leads to severe EDS because of modification by G530S, which alone causes only thin skin and delayed wound healing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10602121" 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> rs786205100 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205100;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/rs786205100?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=rs786205100" 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=rs786205100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>One of the patients (P1) with classic EDS (EDSCL1; <a href="/entry/130000">130000</a>) studied by <a href="#16" class="mim-tip-reference" title="Schwarze, U., Atkinson, M., Hoffman, G. G., Greenspan, D. S., Byers, P. H. <strong>Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II).</strong> Am. J. Hum. Genet. 66: 1757-1765, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10796876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10796876</a>] [<a href="https://doi.org/10.1086/302933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10796876">Schwarze et al. (2000)</a> had a deletion of 1 cytosine from a run of 6 cytosines in exon 48 of the COL5A1 gene, resulting in a TAG (stop) codon in exon 48. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10796876" 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">rs121912933 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912933;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=rs121912933" 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=rs121912933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>One of the patients with classic EDS (EDSCL1; <a href="/entry/130000">130000</a>) studied by <a href="#22" class="mim-tip-reference" title="Wenstrup, R. J., Florer, J. B., Willing, M. C., Giunta, C., Steinmann, B., Young, F., Susic, M., Cole, W. G. <strong>COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS.</strong> Am. J. Hum. Genet. 66: 1766-1776, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777716</a>] [<a href="https://doi.org/10.1086/302930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10777716">Wenstrup et al. (2000)</a> had an arg792-to-ter (R792X) mutation in the COL5A1 protein due to a 2603C-T transition in the cDNA (43C-T transition in exon 27 of genomic DNA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777716" 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">rs786205101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205101;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=rs786205101" 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=rs786205101" 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=RCV000018732" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018732" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018732</a>
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<p>In a patient with EDS I (EDSCL1; <a href="/entry/130000">130000</a>), <a href="#21" class="mim-tip-reference" title="Takahara, K., Schwarze, U., Imamura, Y., Hoffman, G. G., Toriello, H., Smith, L. T., Byers, P. H., Greenspan, D. S. <strong>Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha-1(V) N-propeptides and Ehlers-Danlos syndrome type I.</strong> Am. J. Hum. Genet. 71: 451-465, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12145749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12145749</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12145749[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/10.1086/342099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12145749">Takahara et al. (2002)</a> identified a novel splice acceptor mutation (IVS4-2A-G) in the N-propeptide-encoding region of the COL5A1 gene. The outcome of this mutation was complex: in the major product, both exons 5 and 6 were skipped; other products included a small amount in which only exon 5 was skipped and an even smaller amount in which cryptic acceptor sites within exon 5 were used. All products were in frame. Pro-alpha-1(V) chains with abnormal N-propeptides were secreted and were incorporated into extracellular matrix, and the mutation resulted in dramatic alterations in collagen fibril structure. The 2-exon skip occurred in transcripts in which intron 5 was removed rapidly relative to introns 4 and 6, leaving a large (270 nucleotide) composite exon that could be skipped in its entirety. The transcripts in which only exon 5 was skipped were derived from those in which intron 6 was removed before intron 5. The use of cryptic acceptor sites in exon 5 occurred in transcripts in which intron 4 was removed subsequent to introns 5 and 6. These findings suggested that the order of intron removal plays an important role in the outcome of splice site mutations and provided a model that explained why multiple products derive from a mutation at a single splice site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12145749" 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">rs786205102 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205102;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=rs786205102" 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=rs786205102" 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=RCV000018733" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018733" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018733</a>
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<p><a href="#14" class="mim-tip-reference" title="Pallotta, R., Ehresmann, T., Fusilli, P., De Paepe, A., Nuytinck, L. <strong>Discordance between phenotypic appearance and genotypic findings in a familial case of classical Ehlers-Danlos syndrome. (Letter)</strong> Am. J. Med. Genet. 2004 128A: 436-438, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15264295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15264295</a>] [<a href="https://doi.org/10.1002/ajmg.a.20576" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15264295">Pallotta et al. (2004)</a> described a 2-generation family with EDS in which 2 children exhibited features suggestive of EDS I (EDSCL1; <a href="/entry/130000">130000</a>) and their mother exhibited features more suggestive of EDS IV (<a href="/entry/130050">130050</a>), i.e., she had thin nose and thin lips, thin translucent skin with prominent vasculature, and acroosteolysis. No mutation was identified in the COL3A1 gene (<a href="/entry/120180">120180</a>), but a 1-bp deletion in the COL5A1 gene (IVS55-1g) was detected in all 3 affected family members. The molecular diagnosis allowed the investigators to categorize the family into the classic form of EDS, which is associated with a good long-term prognosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15264295" 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 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</strong>
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COL5A1, ARG1062TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906606 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906606;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=rs387906606" 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=rs387906606" 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=RCV000199830 OR RCV001290027" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000199830, RCV001290027" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000199830...</a>
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<p>In a 42-year-old German man with Ehlers-Danlos syndrome (EDSCL1; <a href="/entry/130000">130000</a>), who had spontaneous rupture of the left common iliac artery but was negative for mutation in the COL3A1 gene (<a href="/entry/120180">120180</a>), <a href="#2" class="mim-tip-reference" title="Borck, G., Beighton, P., Wilhelm, C., Kohlhase, J., Kubisch, C. <strong>Arterial rupture in classic Ehlers-Danlos syndrome with COL5A1 mutation.</strong> Am. J. Med. Genet. 152A: 2090-2093, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20635400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20635400</a>] [<a href="https://doi.org/10.1002/ajmg.a.33541" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20635400">Borck et al. (2010)</a> identified heterozygosity for a 3184C-T transition in exon 40 of the COL5A1 gene, resulting in an arg1062-to-ter (R1062X) substitution. The mutation was not found in his unaffected parents, but was present in his 2 children, who had smooth skin and a history of easy bruising. The authors stated that this was the first report of a patient with COL5A1 mutation-positive EDS and rupture of a large artery, suggesting that arterial rupture might be a rare complication of classic EDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20635400" 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 FIBROMUSCULAR DYSPLASIA, MULTIFOCAL</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">rs878853652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs878853652;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=rs878853652" 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=rs878853652" 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=RCV000999270 OR RCV001420510 OR RCV002229642" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000999270, RCV001420510, RCV002229642" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000999270...</a>
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<p>In 4 unrelated patients (probands 1 to 4) with multifocal fibromuscular dysplasia (FMDMF; <a href="/entry/619329">619329</a>) and arterial vascular disease, including tortuosity, aneurysm, dissection, and rupture, <a href="#15" class="mim-tip-reference" title="Richer, J., Hill, H. L., Wang, Y., Yang, M.-L., Hunker, K. L., Lane, J., Blackburn, S., Coleman, D. M., Eliason, J., Sillon, G., D'Agostino, M.-D., Jetty, P., and 16 others. <strong>A novel recurrent COL5A1 genetic variant is associated with a dysplasia-associated arterial disease exhibiting dissections and fibromuscular dysplasia.</strong> Arterioscler. Thromb. Vasc. Biol. 40: 2686-2699, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32938213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32938213</a>] [<a href="https://doi.org/10.1161/ATVBAHA.119.313885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32938213">Richer et al. (2020)</a> identified heterozygosity for a c.1540G-A transition (c.1540G-A, NM_000093.3) in exon 12 of the COL5A1 gene, resulting in a gly514-to-ser (G514S) substitution involving the penultimate glycine of the first triple-helical repeat within the interrupted collagenous region. Ancestry analysis revealed the probands to be of central European ancestry, and all 4 shared a 160.1-kb haplotype containing G514S. The mutation, which was not found in the gnomAD database, was present in 2 affected members of family 1 with incomplete penetrance: the proband's 24-year-old daughter and 40-year-old nephew both had hyperextensible skin and hypermobile joints, and the daughter showed vascular tortuosity, but neither had experienced arterial dissection. The G514S variant was also reported in the ClinVar database in a female patient with joint pain and normal aortic dimensions on echocardiography; no other vascular imaging was pursued. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32938213" 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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Baghdadi, M. B., Castel, D., Machado, L., Fukada, S., Birk, D. E., Relaix, F., Tajbakhsh, S., Mourikis, P.
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<strong>Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.</strong>
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Nature 557: 714-718, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29795344" 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/s41586-018-0144-9" target="_blank">Full Text</a>]
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<strong>Arterial rupture in classic Ehlers-Danlos syndrome with COL5A1 mutation.</strong>
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Am. J. Med. Genet. 152A: 2090-2093, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20635400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20635400</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20635400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33541" target="_blank">Full Text</a>]
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<strong>A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.</strong>
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Am. J. Hum. Genet. 63: 390-398, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683580" 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/10.1086/301948" target="_blank">Full Text</a>]
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Burrows, N. P., Nicholls, A. C., Yates, J. R. W., Gatward, G., Sarathachandra, P., Richards, A., Pope, F. M.
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<strong>The gene encoding collagen alpha-1(V) (COL5A1) is linked to mixed Ehlers-Danlos syndrome type I/II.</strong>
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J. Invest. Derm. 106: 1273-1276, 1996.
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[<a href="https://doi.org/10.1111/1523-1747.ep12348978" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00210769" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0945-053x(05)80001-0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(sici)1096-8628(20000103)90:1<72::aid-ajmg13>3.0.co;2-c" target="_blank">Full Text</a>]
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<strong>Human collagen gene COL5A1 maps to the q34.2-q34.3 region of chromosome 9, near the locus for nail-patella syndrome.</strong>
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[<a href="https://doi.org/10.1016/0888-7543(92)90320-r" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(95)80021-d" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1993.1270" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.33.11.940" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20576" target="_blank">Full Text</a>]
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<strong>A novel recurrent COL5A1 genetic variant is associated with a dysplasia-associated arterial disease exhibiting dissections and fibromuscular dysplasia.</strong>
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[<a href="https://doi.org/10.1161/ATVBAHA.119.313885" target="_blank">Full Text</a>]
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<strong>Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II).</strong>
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[<a href="https://doi.org/10.1086/302933" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1096-8628(20000814)93:4<342::aid-ajmg16>3.0.co;2-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.22137" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12145749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12145749</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12145749[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=12145749" 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/10.1086/342099" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Wenstrup2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wenstrup, R. J., Florer, J. B., Willing, M. C., Giunta, C., Steinmann, B., Young, F., Susic, M., Cole, W. G.
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<strong>COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS.</strong>
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Am. J. Hum. Genet. 66: 1766-1776, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777716</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777716" 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/10.1086/302930" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Wenstrup1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wenstrup, R. J., Langland, G. T., Willing, M. C., D'Souza, V. N., Cole, W. G.
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<strong>A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-alpha-1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I).</strong>
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Hum. Molec. Genet. 5: 1733-1736, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/5.11.1733" target="_blank">Full Text</a>]
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</p>
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</ol>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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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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Marla J. F. O'Neill - updated : 05/17/2021
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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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Ada Hamosh - updated : 08/14/2018<br>Nara Sobreira - updated : 2/25/2013<br>Marla J. F. O'Neill - updated : 2/3/2011<br>Kelly A. Przylepa - updated : 4/13/2007<br>Cassandra L. Kniffin - updated : 10/10/2005<br>Victor A. McKusick - updated : 9/16/2002<br>Victor A. McKusick - updated : 7/25/2000<br>Victor A. McKusick - updated : 12/29/1999<br>Victor A. McKusick - updated : 7/17/1998<br>Victor A. McKusick - updated : 3/12/1997<br>Moyra Smith - updated : 1/29/1997<br>Alan F. Scott - updated : 11/8/1995
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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="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">
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Victor A. McKusick : 10/1/1991
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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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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<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 : 05/18/2021
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</span>
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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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alopez : 05/17/2021<br>carol : 11/14/2018<br>alopez : 08/14/2018<br>carol : 04/05/2018<br>carol : 12/21/2017<br>carol : 11/30/2015<br>carol : 4/13/2015<br>carol : 3/20/2013<br>carol : 2/25/2013<br>carol : 6/1/2012<br>terry : 5/10/2012<br>wwang : 2/8/2011<br>terry : 2/3/2011<br>carol : 2/2/2009<br>carol : 4/18/2007<br>carol : 4/13/2007<br>alopez : 11/11/2005<br>carol : 10/19/2005<br>carol : 10/12/2005<br>ckniffin : 10/10/2005<br>mgross : 9/16/2002<br>carol : 9/16/2002<br>ckniffin : 5/29/2002<br>carol : 7/11/2001<br>carol : 8/1/2000<br>carol : 8/1/2000<br>terry : 7/25/2000<br>carol : 1/6/2000<br>mcapotos : 1/6/2000<br>mcapotos : 1/6/2000<br>mcapotos : 1/3/2000<br>terry : 12/29/1999<br>dkim : 12/16/1998<br>dkim : 12/10/1998<br>dkim : 12/9/1998<br>dkim : 12/9/1998<br>terry : 8/5/1998<br>alopez : 7/17/1998<br>alopez : 7/17/1998<br>terry : 7/17/1998<br>terry : 5/29/1998<br>terry : 3/17/1997<br>terry : 3/12/1997<br>terry : 3/11/1997<br>mark : 1/29/1997<br>terry : 1/28/1997<br>mark : 1/28/1997<br>terry : 1/27/1997<br>jamie : 1/21/1997<br>jamie : 1/21/1997<br>terry : 1/14/1997<br>terry : 11/15/1996<br>terry : 11/6/1996<br>terry : 9/4/1996<br>terry : 4/22/1996<br>mark : 12/15/1995<br>terry : 12/6/1995<br>mark : 10/13/1995<br>terry : 11/18/1994<br>jason : 6/7/1994<br>carol : 7/13/1993<br>carol : 6/4/1993
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</span>
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 120215
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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COLLAGEN, TYPE V, ALPHA-1; COL5A1
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</span>
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</h3>
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: COL5A1</em></strong>
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</span>
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</p>
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</div>
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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: 9q34.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:134,641,803-134,844,843 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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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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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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9q34.3
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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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Ehlers-Danlos syndrome, classic type, 1
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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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130000
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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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Autosomal dominant
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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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3
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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Fibromuscular dysplasia, multifocal
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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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619329
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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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Autosomal dominant
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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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3
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</span>
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</tbody>
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</table>
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<br />
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</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>Type V collagen was first identified in human placenta and adult skin, but later studies showed that it is present in many other tissues and organs as a minor collagen component. Type V collagen occurs as heterotrimers of 3 different polypeptide chains, alpha-1, alpha-2 (COL5A2; 120190), and alpha-3 (COL5A3; 120216), or 2 copies of alpha-1 and 1 copy of alpha-2; it also occurs as a homotrimer of alpha-1 polypeptides. Takahara et al. (1991) reported the sequence of cDNA encoding the complete prepro-alpha-1(V) chain. The collagenous region and COOH-terminal noncollagenous region closely resembled that of the alpha-1(XI) (120280) chain; however, codon usage differed, suggesting that the COL5A1 gene is evolutionarily distinct. </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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<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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</div>
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<span class="mim-text-font">
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<p>Using cDNA and genomic clones for the COL5A1 gene as probes, Greenspan et al. (1992) determined in panels of human-mouse hybrid cell lines and by in situ hybridization experiments that the COL5A1 gene is located in the segment 9q34.2-q34.3. Caridi et al. (1992) likewise assigned the COL5A1 gene to 9q34.3 by in situ hybridization. Mattei et al. (1993) found that the homologous gene in the mouse is located in the A2-B region of chromosome 2. They independently confirmed the localization of the human gene to 9q34. </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>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>Takahara et al. (1995) determined the complete genomic structure of COL5A1 and showed that the gene is more complex than other fibrillar collagen genes, having 66 exons compared to 52. The gene spans at least 750 kb. </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>Gene Function</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>Fichard et al. (1995) reviewed collagens V and XI and commented on their fundamental role in the control of fibrillogenesis, probably by forming a core within the fibrils. Another characteristic of these collagens is the partial retention of their N-propeptide extensions in tissue forms, which is unusual for known fibrillar collagens. The tissue locations of collagen V and XI are different, but their structural and biologic properties seem to be closely related. Their primary structures are highly conserved at both the gene and the protein level, and this conservation is the basis of their similar biologic properties. In particular, they are both resistant to mammalian collagenases, and surprisingly sensitive to trypsin. Although they have both cell adhesion and heparin binding sites that could be crucial in physiologic processes such as development and wound healing, the 2 collagens are usually buried within the major collagen fibrils. It had become evident that several collagen-type molecules are, in fact, heterotypic associations of chains from both collagens V and XI, demonstrating that these 2 collagens are not distinct types but a single type that can be called collagen V/XI. </p><p>Baghdadi et al. (2018) showed that adult muscle satellite cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, Baghdadi et al. (2018) identified NOTCH1 (190198)/RBPJ (147183)-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, Baghdadi et al. (2018) showed that collagen V produced by satellite cells is a critical component of the quiescent niche, as depletion of collagen V by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of collagen V with satellite cells is mediated by the calcitonin receptor (CALCR; 114131), for which collagen V acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in collagen V-null satellite cells. Baghdadi et al. (2018) concluded that their study revealed a Notch-COLV-calcitonin receptor signaling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion. </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>Molecular Genetics</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><strong><em>Ehlers-Danlos Syndrome, Classic Type 1</em></strong></p><p>
|
|
Nicholls et al. (1994) identified molecular abnormalities in type V collagen in 2 patients with Ehlers-Danlos syndrome. The first patient, with overlapping clinical features of both EDS I/II (EDSCL1; 130000) and EDS VII (see 130060) and additional unusual corneal abnormalities, was heterozygous for a G(+3)-to-T change in the 5-prime splice site leading to deletion of the upstream exon (120215.0001). The in-frame 54-bp deletion eliminated 6 Gly-X-Y triplets from the triple helical domain. The second patient also showed clinical features of EDS I/II and had, in addition, vascular weakness similar to the EDS IV (130050) subtype. Both the alpha-1 and the alpha-2 chains of type V collagen ran with lower mobility than normal on SDS-page gels, indicative of excessive posttranslational modification of the protein due to a point mutation in 1 of the protein chains.</p><p>Using a polymorphic intragenic simple sequence repeat at the COL5A1 locus, Burrows et al. (1996) demonstrated tight linkage to EDS I/II in a 3-generation family, giving a lod score of 4.07 at zero recombination. The variation in expression in this family suggested that EDS types I and II are allelic, and the linkage data supported the hypothesis that mutation in COL5A1 can cause both phenotypes. That this was indeed the case was demonstrated by Nicholls et al. (1996) who, in a patient with clinical features of Ehlers-Danlos syndrome type I/II and VII, demonstrated an exon-skipping mutation in the COL5A1 gene (120215.0001). </p><p>Wenstrup et al. (1996) demonstrated that affected individuals in an EDS I COL5A1-linked family were heterozygous for a 4-bp deletion in intron 65 (120215.0002). This deletion led to a 234-bp deletion of exon 65 in the processed mRNA for pro-alpha-1(V) collagen. </p><p>De Paepe et al. (1997) likewise identified a mutation in COL5A1 segregating with EDS I in a 4-generation family (120215.0003). In addition, they detected splicing defects in the COL5A1 gene in a patient with EDS I and in a family with EDS II (120215.0005). Thus they proved that EDS I and II are allelic disorders. </p><p>To determine whether allele-product instability could explain failure to identify some mutations in the COL5A1 gene in classic EDS, Schwarze et al. (2000) analyzed polymorphic variants in the COL5A1 gene in 16 individuals and examined mRNA for the expression of both alleles and for alterations in splicing. They found a splice site mutation in a single individual and determined that, in 6 individuals, the mRNA from one COL5A1 allele either was not expressed or was very unstable. They identified small insertions or deletions in 5 of these cell strains, but were unable to identify the mutation in the sixth individual. Thus, although as many as half of the mutations that give rise to EDS types I and II are likely to lie in the COL5A1 gene, a significant portion of them result in very low levels of mRNA from the mutant allele, as a consequence of nonsense-mediated mRNA decay. </p><p>Similarly, Wenstrup et al. (2000) found that 8 of 28 probands with classic EDS, who were heterozygous for expressed polymorphisms in COL5A1, showed complete or nearly complete loss of expression of one COL5A1 allele. Reduced levels of COL5A1 mRNA relative to levels of COL5A2 mRNA were also observed in the cultured fibroblasts from EDS probands. Products of the 2 COL5A1 alleles were approximately equal after the addition of cycloheximide to the fibroblast cultures. After harvesting of mRNAs from cycloheximide-treated cultured fibroblasts, heteroduplex analysis of overlapping RT-PCR segments spanning the complete COL5A1 cDNA showed anomalies in 4 of the 8 probands, leading to identification of causative mutations; in the remaining 4 probands, targeting of CGA-to-TGA mutations in genomic DNA revealed a premature stop codon in one of them. Wenstrup et al. (2000) estimated that one-third of persons with classic EDS have mutations of the COL5A1 gene that result in haploinsufficiency. These findings indicated that normal formation of the heterotypic collagen fibrils that contain types I, III, and V collagen require the expression of both COL5A1 alleles. </p><p>In a 42-year-old German man with EDS and spontaneous rupture of his left common iliac artery who was negative for mutation in COL3A1 (120180), Borck et al. (2010) identified a de novo heterozygous nonsense mutation (120215.0012) in the COL5A1 gene. The authors stated that this was the first report of a patient with COL5A1 mutation-positive EDS and rupture of a large artery, suggesting that arterial rupture might be a rare complication of classic EDS. </p><p>Symoens et al. (2012) analyzed COL5A1 and COL5A2 in 126 patients with a diagnosis or suspicion of classic EDS. In 93 patients, a type V collagen defect was found, of which 73 were COL5A1 mutations, 13 were COL5A2 mutations, and 7 were COL5A1 null-alleles with mutation unknown. The majority of the 73 COL5A1 mutations generated a COL5A1 null-allele, whereas one-third were structural mutations, scattered throughout COL5A1. All COL5A2 mutations were structural mutations. Reduced availability of type V collagen appeared to be the major disease-causing mechanism, besides other intra- and extracellular contributing factors. All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring, and joint hypermobility. No COL5A1/COL5A2 mutation was detected in 24 patients who displayed skin and joint hyperextensibility but lacked dystrophic scarring. Overall, over 90% of patients fulfilling all major Villefranche criteria for classic EDS were shown to harbor a type V collagen defect, indicating that this is the major, if not the only, cause of classic EDS. </p><p><strong><em>Multifocal Fibromuscular Dysplasia</em></strong></p><p>
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In 4 unrelated patients with multifocal fibromuscular dysplasia (FMDMF; 619329), Richer et al. (2020) identified heterozygosity for a missense mutation in the COL5A1 gene (G514S; 120215.0013). Ancestry analysis revealed a shared haplotype, suggesting a common founder. The mutation, which was not found in the gnomAD database, segregated with incomplete penetrance in the family of 1 of the probands. In a cohort of 264 unrelated adult patients with FMDMF, 134 of whom had dissections or macroaneurysms, the authors observed a higher burden of low-frequency COL5A1 variants, of unclear clinical significance but predicted to be deleterious, in patients who had experienced an arterial dissection. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
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Greenspan et al. (1995) used 3-prime untranslated region RFLPs to exclude the COL5A1 gene as a candidate in families with tuberous sclerosis-1 (191100), Ehlers-Danlos syndrome type II, and the nail-patella syndrome (161200). In addition, they described a polymorphic simple sequence repeat (SSR) within a COL5A1 intron. They used this SSR to exclude COL5A1 as a candidate gene also in hereditary hemorrhagic telangiectasia (187300), and to add COL5A1 to the index markers of chromosome 9 by evaluation of the COL5A1 locus on the CEPH 40-family reference pedigree set. This genetic mapping placed COL5A1 between markers D9S66 and D9S67. </p>
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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>13 Selected Examples):</strong>
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</span>
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</h4>
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<p />
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<h4>
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<span class="mim-font">
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<strong>.0001 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, IVS49DS, G-T, +3
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<br />
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SNP: rs786200922,
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ClinVar: RCV000018723, RCV000578847
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</span>
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<span class="mim-text-font">
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<p>Nicholls et al. (1996) demonstrated a defect in COL5A1 in a 24-year-old woman with many features of the Ehlers-Danlos syndrome (EDSCL1; 130000). She showed generalized skin fragility with extensive scarring of the forehead, shins, and knees, and scattered bruising on the arms and legs. She had marked generalized joint laxity with severe bilateral hallux valgus and diamond-shaped feet. She was short (155 cm), with mild thoracic kyphoscoliosis, pectus excavatum, and audible mitral valve prolapse. The eyes were unusually prominent and ophthalmologic examination demonstrated hypermetropia caused by flattened corneas. Because of the short stature and scoliosis, the differential diagnosis initially favored EDS VII (225410), but the cutaneous fragility and other features were also consistent with EDS types I and II. Electron microscopy of skin tissue indicated abnormal collagen fibrillogenesis with longitudinal sections showing a marked disruption of fibril packing, giving very irregular outlines to transverse sections. Nicholls et al. (1996) analyzed the collagens produced by cultured fibroblasts and found that the type V collagen had a population of alpha-1(V) chains shorter than normal. Peptide mapping suggested a deletion within the triple helical domain. RT-PCR amplification of mRNA covering the whole of this domain of COL5A1 showed a deletion of 54 bp. Takahara et al. (1995) had reported that exon 49 is 54 bp long. Nicholls et al. (1996) stated that although 6 Gly-X-Y triplets were lost from the domain, the essential triplet amino acid sequence and C-propeptide structure were maintained, allowing mutant protein chains to be incorporated into triple helices. Genomic DNA analysis identified a de novo G-to-T transversion at position +3 in a 5-prime splice site of one COL5A1 allele. The authors noted that similar mutations causing exon skipping in the major collagen genes, COL1A1 (120150), COL1A2 (120160), and COL3A1 (120180), have been identified in several cases of osteogenesis imperfecta and EDS type IV. These observations supported the hypothesis that type V, although quantitatively a minor collagen, has a critical role in the formation of fibrillar collagen matrix. </p>
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</span>
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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 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, IVS65DS, 4-BP DEL, +3 TO +6
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<br />
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SNP: rs786200923,
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ClinVar: RCV000018724
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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 2 families with EDS type I (EDSCL1; 130000) linked to the COL5A1 gene, Wenstrup et al. (1996) reported a 4-bp deletion of nucleotides +3 to +6 in intron 65. The mutation caused a 234-bp deletion of exon 65 in the processed mRNA. They reported that this in-frame mutation predicts a pro-alpha-1(V) chain in which the C-propeptide is shortened by 78 amino acids. They noted that the deleted segment contains 2 of 8 highly conserved cysteine residues that are thought to participate in disulfhydryl bonds and facilitate chain association during molecular assembly. </p>
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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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<h4>
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<span class="mim-font">
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<strong>.0003 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, CYS1181SER
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<br />
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SNP: rs80338764,
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ClinVar: RCV000032107, RCV001290029
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</span>
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<div>
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<span class="mim-text-font">
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<p>De Paepe et al. (1997) identified a G-to-T transversion in the codon for cysteine-1181 (TGC) to the codon for serine (TCC). This represented a substitution of the most 5-prime cysteine residue within a highly conserved sequence of the C-propeptide domain of the pro-alpha-1(V) chain. The mutation thus caused reduction of collagen V by preventing incorporation of the mutant chains in the collagen V trimers. The patients were members of a family in which 7 individuals of 4 generations were affected with typical changes of type I EDS (EDSCL1; 130000). </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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<h4>
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<span class="mim-font">
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<strong>.0004 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, EX42DEL, SPLICE MUTATION
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<br />
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SNP: rs2132830442,
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ClinVar: RCV000018726
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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>De Paepe et al. (1997) identified a de novo splicing mutation in a 13-year-old girl with classic features of EDS I (EDSCL1; 130000). She was born prematurely after premature rupture of membranes with an umbilical hernia and bilateral dislocation of the hips. A deletion of exon 42 was demonstrated, resulting in the loss of approximately 100 bp. The mutation causing the deletion of exon 42 remained to be defined, as no sequence abnormalities in exon 42 or in the flanking 3-prime and 5-prime splice sites or the branch site were found. </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 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, IVS64AS, T-A, -11
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<br />
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SNP: rs183495554,
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gnomAD: rs183495554,
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ClinVar: RCV000018727
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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>De Paepe et al. (1997) found a splicing mutation in the COL5A1 gene in a man in whom EDS type II (EDSCL1; 130000) had been diagnosed at the age of 23 years because of a history of easy bruising and abnormal scarring and several luxations of the ankles while playing basketball. At age 32 years, he presented with moderate skin hyperextensibility and joint laxity and several pigmented paper scars on knees and shins. His 2 affected sons, aged 9 and 16 years, showed mild skin hyperextensibility, hyperlaxity of several joints, poor wound healing, and several ecchymoses and atrophic scars on the lower legs. A T-to-A transversion was found at position -11 of the 3-prime splice site of exon 65. The mutation caused abnormal splicing of the COL5A1 gene yielding 2 different mRNA products. One mRNA contained a 9-bp insertion because of the use of a new 3-prime splice site within IVS64. The second mRNA contained a deletion of 45 nucleotides at the 3-prime end of exon 65 because of the use of a cryptic splice site within exon 65. The mutation created a BsrI restriction site, which allowed De Paepe et al. (1997) to confirm the presence of the mutation in the affected sons and absence of the mutation in 30 control individuals. </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 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, IVS32AS, T-G, -25
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<br />
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SNP: rs765079080,
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gnomAD: rs765079080,
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ClinVar: RCV001290028
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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>Using an intragenic COL5A1 polymorphism, Burrows et al. (1998) demonstrated linkage, at zero recombination, to the same allele in 2 large British EDS type II (EDSCL1; 130000) families (lod scores 4.1 and 4.3). Affected members of each family were heterozygous for a point mutation in intron 32, causing the 45-bp exon 33 to be lost from the mRNA in approximately 60% of transcripts from the mutant gene. This mutation lies only 2 bp upstream of a highly conserved adenosine in the consensus branch-site sequence, which is required for lariat formation. Although both families shared the same marker allele, Burrows et al. (1998) were unable to identify a common genealogy. This was the first description of a mutation at the lariat branch site, which plays a pivotal role in the splicing mechanism, in a collagen gene. (Mutations at the lariat branch site have been identified in the LCAT (606967), L1CAM (308840), and FBN2 (612570) genes.) Burrows et al. (1998) suggested that the in-frame exon skipping produced by the mutation had a dominant-negative effect due to incorporation of the mutant pro-alpha chain into the triple-helical molecule. The mutation in this case was a T-to-G transversion at position -25 in intron 32. Burrows et al. (1998) examined 11 affected members of one family and 8 affected members of the second. All fulfilled the clinical criteria for EDS type II (130000), namely, atrophic scarring confined to elbows and knees, evidence or history of easy bruising, joint laxity, and moderate cutaneous hyperextensibility. </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>.0007 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, GLY1489GLU
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<br />
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SNP: rs121912932,
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ClinVar: RCV000018729
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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>Giunta and Steinmann (2000) observed compound heterozygosity for a gly1489-to-glu (G1489E) mutation and a gly530-to-ser (G530S) mutation. (The former mutation was originally published as G1489D; a correction was published as a letter (Steinmann and Giunta, 2000).) The former mutation represented the first report of a glycine substitution in the main triple-helical region of COL5A1. The latter mutation was located in the NH2-terminal domain. The compound heterozygous father, the proband, had typical type I EDS (EDSCL1; 130000). He had presented with microcornea at the age of 35 years at which time the skin was hyperelastic with numerous atrophic and hemosiderotic scars on the forehead, elbows, and legs, as well as molluscoid pseudotumors on the elbows, knees, heels, and toes. At the age of 57 years, he presented with secondary cutis laxa (e.g., of the eyelids), gross varicosities of the legs, and bladder diverticula leading to recurrent urinary tract infections. He had 2 daughters. The one daughter who inherited the G1489E mutation had milder expression of EDS. She was born 4 weeks before term because of premature rupture of the membranes. Muscular hypotonia was marked, necessitating feeding by a nasogastric tube, and was associated with a delay in gross motor development. At age 6, her skin was velvety, hyperelastic, and fragile, with atrophic and hemosiderotic scars on forehead, chin, and shins, and molluscoid pseudotumors on the elbows. There was marked joint hypermobility, and she had microcorneas. At age 20, she was clearly less severely affected than her father, with few abnormal scars, fewer molluscoid pseudotumors, and lesser skin hyperelasticity. The other daughter, who inherited the G530S mutation, and the proband's mother, from whom he had inherited the G530S mutation, presented with thin and smooth skin and delayed wound healing; the skin was not hyperelastic and did not present abnormal scars. The proband's father, from whom he presumably inherited the G1489E mutation, died at age 54 years of renal failure due to reflux nephropathy thought to be related to EDS. Giunta and Steinmann (2000) found the G530S substitution in 1 of 51 control individuals. This person was a healthy man without obvious connective tissue disorder; however, he had soft and hyperelastic skin without abnormal scars. His joints were not hypermobile. </p><p>Giunta and Steinmann (2000) pointed out that the NH2-terminal domain plays a crucial role in modulating fibril formation; hence, the G530S substitution may alter the structure and function of this region and consequently the formation of collagen fibrils. The combination of mutations leads to severe EDS because of modification by G530S, which alone causes only thin skin and delayed wound healing. </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>.0008 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</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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COL5A1, 1-BP DEL
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<br />
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SNP: rs786205100,
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gnomAD: rs786205100,
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ClinVar: RCV000018730
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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>One of the patients (P1) with classic EDS (EDSCL1; 130000) studied by Schwarze et al. (2000) had a deletion of 1 cytosine from a run of 6 cytosines in exon 48 of the COL5A1 gene, resulting in a TAG (stop) codon in exon 48. </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 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
COL5A1, ARG792TER
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|
|
<br />
|
|
|
|
SNP: rs121912933,
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|
|
|
|
|
|
|
ClinVar: RCV000018731, RCV002276558
|
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|
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</span>
|
|
</div>
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|
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<div>
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<span class="mim-text-font">
|
|
<p>One of the patients with classic EDS (EDSCL1; 130000) studied by Wenstrup et al. (2000) had an arg792-to-ter (R792X) mutation in the COL5A1 protein due to a 2603C-T transition in the cDNA (43C-T transition in exon 27 of genomic DNA). </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 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL5A1, IVS4AS, A-G, -2
|
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|
|
<br />
|
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|
|
SNP: rs786205101,
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|
|
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|
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ClinVar: RCV000018732
|
|
|
|
|
|
</span>
|
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</div>
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|
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a patient with EDS I (EDSCL1; 130000), Takahara et al. (2002) identified a novel splice acceptor mutation (IVS4-2A-G) in the N-propeptide-encoding region of the COL5A1 gene. The outcome of this mutation was complex: in the major product, both exons 5 and 6 were skipped; other products included a small amount in which only exon 5 was skipped and an even smaller amount in which cryptic acceptor sites within exon 5 were used. All products were in frame. Pro-alpha-1(V) chains with abnormal N-propeptides were secreted and were incorporated into extracellular matrix, and the mutation resulted in dramatic alterations in collagen fibril structure. The 2-exon skip occurred in transcripts in which intron 5 was removed rapidly relative to introns 4 and 6, leaving a large (270 nucleotide) composite exon that could be skipped in its entirety. The transcripts in which only exon 5 was skipped were derived from those in which intron 6 was removed before intron 5. The use of cryptic acceptor sites in exon 5 occurred in transcripts in which intron 4 was removed subsequent to introns 5 and 6. These findings suggested that the order of intron removal plays an important role in the outcome of splice site mutations and provided a model that explained why multiple products derive from a mutation at a single splice site. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
COL5A1, IVS55, 1-BP DEL, G, -1
|
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|
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<br />
|
|
|
|
SNP: rs786205102,
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|
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|
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|
|
ClinVar: RCV000018733
|
|
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|
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</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Pallotta et al. (2004) described a 2-generation family with EDS in which 2 children exhibited features suggestive of EDS I (EDSCL1; 130000) and their mother exhibited features more suggestive of EDS IV (130050), i.e., she had thin nose and thin lips, thin translucent skin with prominent vasculature, and acroosteolysis. No mutation was identified in the COL3A1 gene (120180), but a 1-bp deletion in the COL5A1 gene (IVS55-1g) was detected in all 3 affected family members. The molecular diagnosis allowed the investigators to categorize the family into the classic form of EDS, which is associated with a good long-term prognosis. </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>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL5A1, ARG1062TER
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|
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|
|
<br />
|
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|
|
SNP: rs387906606,
|
|
|
|
|
|
|
|
ClinVar: RCV000199830, RCV001290027
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 42-year-old German man with Ehlers-Danlos syndrome (EDSCL1; 130000), who had spontaneous rupture of the left common iliac artery but was negative for mutation in the COL3A1 gene (120180), Borck et al. (2010) identified heterozygosity for a 3184C-T transition in exon 40 of the COL5A1 gene, resulting in an arg1062-to-ter (R1062X) substitution. The mutation was not found in his unaffected parents, but was present in his 2 children, who had smooth skin and a history of easy bruising. The authors stated that this was the first report of a patient with COL5A1 mutation-positive EDS and rupture of a large artery, suggesting that arterial rupture might be a rare complication of classic EDS. </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>.0013 FIBROMUSCULAR DYSPLASIA, MULTIFOCAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
COL5A1, GLY514SER
|
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|
|
<br />
|
|
|
|
SNP: rs878853652,
|
|
|
|
|
|
|
|
ClinVar: RCV000999270, RCV001420510, RCV002229642
|
|
|
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|
|
</span>
|
|
</div>
|
|
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<div>
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<span class="mim-text-font">
|
|
<p>In 4 unrelated patients (probands 1 to 4) with multifocal fibromuscular dysplasia (FMDMF; 619329) and arterial vascular disease, including tortuosity, aneurysm, dissection, and rupture, Richer et al. (2020) identified heterozygosity for a c.1540G-A transition (c.1540G-A, NM_000093.3) in exon 12 of the COL5A1 gene, resulting in a gly514-to-ser (G514S) substitution involving the penultimate glycine of the first triple-helical repeat within the interrupted collagenous region. Ancestry analysis revealed the probands to be of central European ancestry, and all 4 shared a 160.1-kb haplotype containing G514S. The mutation, which was not found in the gnomAD database, was present in 2 affected members of family 1 with incomplete penetrance: the proband's 24-year-old daughter and 40-year-old nephew both had hyperextensible skin and hypermobile joints, and the daughter showed vascular tortuosity, but neither had experienced arterial dissection. The G514S variant was also reported in the ClinVar database in a female patient with joint pain and normal aortic dimensions on echocardiography; no other vascular imaging was pursued. </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>REFERENCES</strong>
|
|
</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Baghdadi, M. B., Castel, D., Machado, L., Fukada, S., Birk, D. E., Relaix, F., Tajbakhsh, S., Mourikis, P.
|
|
<strong>Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.</strong>
|
|
Nature 557: 714-718, 2018.
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|
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[PubMed: 29795344]
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|
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[Full Text: https://doi.org/10.1038/s41586-018-0144-9]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Borck, G., Beighton, P., Wilhelm, C., Kohlhase, J., Kubisch, C.
|
|
<strong>Arterial rupture in classic Ehlers-Danlos syndrome with COL5A1 mutation.</strong>
|
|
Am. J. Med. Genet. 152A: 2090-2093, 2010.
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[PubMed: 20635400]
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[Full Text: https://doi.org/10.1002/ajmg.a.33541]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Burrows, N. P., Nicholls, A. C., Richards, A. J., Luccarini, C., Harrison, J. B., Yates, J. R. W., Pope, F. M.
|
|
<strong>A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.</strong>
|
|
Am. J. Hum. Genet. 63: 390-398, 1998.
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[PubMed: 9683580]
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[Full Text: https://doi.org/10.1086/301948]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Burrows, N. P., Nicholls, A. C., Yates, J. R. W., Gatward, G., Sarathachandra, P., Richards, A., Pope, F. M.
|
|
<strong>The gene encoding collagen alpha-1(V) (COL5A1) is linked to mixed Ehlers-Danlos syndrome type I/II.</strong>
|
|
J. Invest. Derm. 106: 1273-1276, 1996.
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[PubMed: 8752669]
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[Full Text: https://doi.org/10.1111/1523-1747.ep12348978]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Caridi, G., Pezzolo, A., Bertelli, R., Gimelli, G., Di Donato, A., Candiano, G., Ghiggeri, G. M.
|
|
<strong>Mapping of the human COL5A1 gene to chromosome 9q34.3.</strong>
|
|
Hum. Genet. 90: 174-176, 1992.
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[PubMed: 1427773]
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[Full Text: https://doi.org/10.1007/BF00210769]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I., Naeyaert, J.-M.
|
|
<strong>Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II.</strong>
|
|
Am. J. Hum. Genet. 60: 547-554, 1997.
|
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|
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[PubMed: 9042913]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Fichard, A., Kleman, J.-P., Ruggiero, F.
|
|
<strong>Another look at collagen V and XI molecules.</strong>
|
|
Matrix Biol. 14: 515-531, 1995.
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|
|
|
[PubMed: 8535602]
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|
|
[Full Text: https://doi.org/10.1016/s0945-053x(05)80001-0]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Giunta, C., Steinmann, B.
|
|
<strong>Compound heterozygosity for a disease-causing G1489E and disease-modifying G530S substitution in COL5A1 of a patient with the classical type of Ehlers-Danlos syndrome: an explanation of intrafamilial variability?</strong>
|
|
Am. J. Med. Genet. 90: 72-79, 2000. Note: Erratum: Am. J. Med. Genet. 93: 342 only, 2000.
|
|
|
|
|
|
[PubMed: 10602121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(20000103)90:1<72::aid-ajmg13>3.0.co;2-c]
|
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|
|
|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Greenspan, D. S., Byers, M. G., Eddy, R. L., Cheng, W., Jani-Sait, S., Shows, T. B.
|
|
<strong>Human collagen gene COL5A1 maps to the q34.2-q34.3 region of chromosome 9, near the locus for nail-patella syndrome.</strong>
|
|
Genomics 12: 836-837, 1992.
|
|
|
|
|
|
[PubMed: 1572660]
|
|
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[Full Text: https://doi.org/10.1016/0888-7543(92)90320-r]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Greenspan, D. S., Northrup, H., Au, K.-S., McAllister, K. A., Francomano, C. A., Wenstrup, R. J., Marchuk, D. A., Kwiatkowski, D. J.
|
|
<strong>COL5A1: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II.</strong>
|
|
Genomics 25: 737-739, 1995.
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|
|
|
[PubMed: 7759113]
|
|
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|
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[Full Text: https://doi.org/10.1016/0888-7543(95)80021-d]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Mattei, M. G., Bruce, B., Karsenty, G.
|
|
<strong>Mouse alpha-1 type V collagen gene maps to the [A2-B] region of chromosome 2.</strong>
|
|
Genomics 16: 786-788, 1993.
|
|
|
|
|
|
[PubMed: 8325657]
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|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1270]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Nicholls, A. C., McCarron, S., Narcisi, P., Pope, F. M.
|
|
<strong>Molecular abnormalities of type V collagen in Ehlers Danlos syndrome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 55 (suppl.): A233, 1994.
|
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Nicholls, A. C., Oliver, J. E., McCarron, S., Harrison, J. B., Greenspan, D. S., Pope, F. M.
|
|
<strong>An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome.</strong>
|
|
J. Med. Genet. 33: 940-946, 1996. Note: Erratum: J. Med. Genet. 334: 87 only, 1997.
|
|
|
|
|
|
[PubMed: 8950675]
|
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|
|
[Full Text: https://doi.org/10.1136/jmg.33.11.940]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Pallotta, R., Ehresmann, T., Fusilli, P., De Paepe, A., Nuytinck, L.
|
|
<strong>Discordance between phenotypic appearance and genotypic findings in a familial case of classical Ehlers-Danlos syndrome. (Letter)</strong>
|
|
Am. J. Med. Genet. 2004 128A: 436-438, 2004.
|
|
|
|
|
|
[PubMed: 15264295]
|
|
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|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20576]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Richer, J., Hill, H. L., Wang, Y., Yang, M.-L., Hunker, K. L., Lane, J., Blackburn, S., Coleman, D. M., Eliason, J., Sillon, G., D'Agostino, M.-D., Jetty, P., and 16 others.
|
|
<strong>A novel recurrent COL5A1 genetic variant is associated with a dysplasia-associated arterial disease exhibiting dissections and fibromuscular dysplasia.</strong>
|
|
Arterioscler. Thromb. Vasc. Biol. 40: 2686-2699, 2020.
|
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|
|
[PubMed: 32938213]
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|
|
[Full Text: https://doi.org/10.1161/ATVBAHA.119.313885]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Schwarze, U., Atkinson, M., Hoffman, G. G., Greenspan, D. S., Byers, P. H.
|
|
<strong>Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II).</strong>
|
|
Am. J. Hum. Genet. 66: 1757-1765, 2000.
|
|
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|
|
[PubMed: 10796876]
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[Full Text: https://doi.org/10.1086/302933]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Steinmann, B., Giunta, C.
|
|
<strong>The devil of the one letter code and the Ehlers-Danlos syndrome: corrigendum. (Letter)</strong>
|
|
Am. J. Med. Genet. 93: 342 only, 2000. Note: Erratum for Am. J. Med. Genet. 90: 72-79, 2000.
|
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|
|
[PubMed: 10946364]
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[Full Text: https://doi.org/10.1002/1096-8628(20000814)93:4<342::aid-ajmg16>3.0.co;2-7]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Symoens, S., Syx, D., Malfait, F., Callewaert, B., De Backer, J., Vanakker, O., Coucke, P., De Paepe, A.
|
|
<strong>Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria.</strong>
|
|
Hum. Mutat. 33: 1485-1493, 2012.
|
|
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|
|
[PubMed: 22696272]
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[Full Text: https://doi.org/10.1002/humu.22137]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Takahara, K., Hoffman, G. G., Greenspan, D. S.
|
|
<strong>Complete structural organization of the human alpha-1(V) collagen gene (COL5A1): divergence from the conserved organization of other characterized fibrillar collagen genes.</strong>
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Genomics 29: 588-597, 1995.
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[PubMed: 8575750]
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[Full Text: https://doi.org/10.1006/geno.1995.9961]
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</p>
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Takahara, K., Sato, Y., Okazawa, K., Okamoto, N., Noda, A., Yaoi, Y., Kato, I.
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<strong>Complete primary structure of human collagen alpha-1(V) chain.</strong>
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[PubMed: 2071595]
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Takahara, K., Schwarze, U., Imamura, Y., Hoffman, G. G., Toriello, H., Smith, L. T., Byers, P. H., Greenspan, D. S.
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<strong>Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha-1(V) N-propeptides and Ehlers-Danlos syndrome type I.</strong>
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Am. J. Hum. Genet. 71: 451-465, 2002.
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[PubMed: 12145749]
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[Full Text: https://doi.org/10.1086/342099]
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Wenstrup, R. J., Florer, J. B., Willing, M. C., Giunta, C., Steinmann, B., Young, F., Susic, M., Cole, W. G.
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<strong>COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS.</strong>
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Am. J. Hum. Genet. 66: 1766-1776, 2000.
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[PubMed: 10777716]
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[Full Text: https://doi.org/10.1086/302930]
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Wenstrup, R. J., Langland, G. T., Willing, M. C., D'Souza, V. N., Cole, W. G.
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<strong>A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-alpha-1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I).</strong>
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Hum. Molec. Genet. 5: 1733-1736, 1996.
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[PubMed: 8923000]
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[Full Text: https://doi.org/10.1093/hmg/5.11.1733]
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Marla J. F. O'Neill - updated : 05/17/2021<br>Ada Hamosh - updated : 08/14/2018<br>Nara Sobreira - updated : 2/25/2013<br>Marla J. F. O'Neill - updated : 2/3/2011<br>Kelly A. Przylepa - updated : 4/13/2007<br>Cassandra L. Kniffin - updated : 10/10/2005<br>Victor A. McKusick - updated : 9/16/2002<br>Victor A. McKusick - updated : 7/25/2000<br>Victor A. McKusick - updated : 12/29/1999<br>Victor A. McKusick - updated : 7/17/1998<br>Victor A. McKusick - updated : 3/12/1997<br>Moyra Smith - updated : 1/29/1997<br>Alan F. Scott - updated : 11/8/1995
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Victor A. McKusick : 10/1/1991
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