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Entry
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- *604580 - FIBULIN 5; FBLN5
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*604580</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="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604580">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>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel-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=ENSG00000140092;t=ENST00000342058" 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=10516" 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=604580" 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 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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</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=ENSG00000140092;t=ENST00000342058" 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_001384158,NM_001384159,NM_001384160,NM_001384161,NM_001384162,NM_006329,XM_011536356" 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_006329" 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=604580" 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=05204&isoform_id=05204_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/FBLN5" 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/3676822,4490530,5305673,12643876,18490145,19743803,28207929,37182914,45503148,48146397,76059429,119601871,119601872,119601873,193786647,193786750,332368209,767979539,1847914279,1847915950,1847916741,1847916925,1847916928,2462538620" 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/Q9UBX5" 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=10516" 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=ENSG00000140092;t=ENST00000342058" 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=FBLN5" 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=FBLN5" 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+10516" 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/FBLN5" 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:10516" 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/10516" 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=chr14&hgg_gene=ENST00000342058.9&hgg_start=91869411&hgg_end=91947694&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/genes/HGNC:3602" 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/fbln5" 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=604580[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>
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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=604580[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000140092" 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=FBLN5" 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=FBLN5" 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=FBLN5" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FBLN5&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/PA28015" 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:3602" 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:1346091" 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/FBLN5#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:1346091" 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/10516/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://www.orthodb.org/?ncbi=10516" 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-041010-54" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=FBLN5&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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604580
|
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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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FIBULIN 5; FBLN5
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
DEVELOPMENTAL ARTERIES AND NEURAL CREST EGF-LIKE; DANCE
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FBLN5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FBLN5</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">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/14/464?start=-3&limit=10&highlight=464">14q32.12</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:91869411-91947694&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'})">14:91,869,411-91,947,694</a> </span>
|
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</em>
|
|
</strong>
|
|
<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>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=614434,619764,219100,608895" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/464?start=-3&limit=10&highlight=464">
|
|
14q32.12
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Cutis laxa, autosomal dominant 2
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614434"> 614434 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, demyelinating, type 1H
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619764"> 619764 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Cutis laxa, autosomal recessive, type IA
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/219100"> 219100 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Macular degeneration, age-related, 3
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/608895"> 608895 </a>
|
|
|
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<p>Members of the fibulin family of proteins, like FBLN5, are extracellular matrix proteins characterized by tandem arrays of EGF (<a href="/entry/131530">131530</a>)-like domains and a C-terminal fibulin (see FBLN1; <a href="/entry/135820">135820</a>)-type module (<a href="#6" class="mim-tip-reference" title="Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. <strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong> J. Biol. Chem. 282: 11805-11816, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>] [<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17324935">Kobayashi et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" 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 a cDNA probe derived from signal sequence trap screening of mouse embryonic heart, EST database screening, and 5-prime RACE, <a href="#13" class="mim-tip-reference" title="Nakamura, T., Ruiz-Lozano, P., Lindner, V., Yabe, D., Taniwaki, M., Furukawa, Y., Kobuke, K., Tashiro, K., Lu, Z., Andon, N. L., Schaub, R., Matsumori, A., Sasayama, S., Chien, K. R., Honjo, T. <strong>DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.</strong> J. Biol. Chem. 274: 22476-22483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10428823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10428823</a>] [<a href="https://doi.org/10.1074/jbc.274.32.22476" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10428823">Nakamura et al. (1999)</a> obtained a cDNA for fibulin-5 (FBLN5), which they called DANCE (for developmental arteries and neural crest EGF-like). The FBLN5 cDNA encodes a deduced 448-amino acid secreted protein with a molecular mass of 66 kD. Its amino acid sequence is 94% identical to that of the mouse Fbln5 protein. It contains 6 calcium-binding EGF-like domains, one of which contains an RGD motif. Northern blot analysis revealed a major transcript of 2.6 kb that is expressed predominantly in heart, ovary, and colon but also in kidney, pancreas, testis, lung, and placenta. FBLN5 is not detectable in brain, liver, thymus, prostate, or peripheral blood leukocytes. FBLN5 is prominently expressed in developing arteries; in adult vessels, its expression is largely diminished but is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10428823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using radioimmunoassays, <a href="#6" class="mim-tip-reference" title="Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. <strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong> J. Biol. Chem. 282: 11805-11816, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>] [<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17324935">Kobayashi et al. (2007)</a> found variable Fbln5 expression in all 14 mouse tissues examined, with highest expression in aorta and lung, and lowest expression in kidney, brain, and thymus. Immunohistochemical analysis localized Fbln5 in perichondrium of developing bone in day-15 mouse embryos and in blood vessel wall, basement membrane, and parabronchial area of the large airway in day-14 mouse embryos. Electron microscopy after rotary shadowing revealed that recombinant mouse Fbln5, like Fbln3 (EFEMP1; <a href="/entry/601548">601548</a>) and Fbln4 (<a href="/entry/604633">604633</a>), appeared as a 20-nm rod with a globular domain at one end, which represented the N-terminal EGF modules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" 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>By FISH, <a href="#13" class="mim-tip-reference" title="Nakamura, T., Ruiz-Lozano, P., Lindner, V., Yabe, D., Taniwaki, M., Furukawa, Y., Kobuke, K., Tashiro, K., Lu, Z., Andon, N. L., Schaub, R., Matsumori, A., Sasayama, S., Chien, K. R., Honjo, T. <strong>DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.</strong> J. Biol. Chem. 274: 22476-22483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10428823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10428823</a>] [<a href="https://doi.org/10.1074/jbc.274.32.22476" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10428823">Nakamura et al. (1999)</a> mapped the FBLN5 gene to chromosome 14q32.1. By FISH and radiation hybrid analysis, <a href="#7" class="mim-tip-reference" title="Kowal, R. C., Jolsin, J. M., Olson, E. N., Schultz, R. A. <strong>Assignment of fibulin-5 (FBLN5) to human chromosome 14q31 by in situ hybridization and radiation hybrid mapping.</strong> Cytogenet. Cell Genet. 87: 2-3, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10640802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10640802</a>] [<a href="https://doi.org/10.1159/000015382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10640802">Kowal et al. (1999)</a> mapped the FBLN5 gene to 14q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10640802+10428823" 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="#13" class="mim-tip-reference" title="Nakamura, T., Ruiz-Lozano, P., Lindner, V., Yabe, D., Taniwaki, M., Furukawa, Y., Kobuke, K., Tashiro, K., Lu, Z., Andon, N. L., Schaub, R., Matsumori, A., Sasayama, S., Chien, K. R., Honjo, T. <strong>DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.</strong> J. Biol. Chem. 274: 22476-22483, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10428823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10428823</a>] [<a href="https://doi.org/10.1074/jbc.274.32.22476" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10428823">Nakamura et al. (1999)</a> showed that FBLN5 promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. The authors suggested that FBLN5 is a novel vascular ligand for integrin receptors and may play a role in vascular development and remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10428823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Mullins, R. F., Olvera, M. A., Clark, A. F., Stone, E. M. <strong>Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration.</strong> Exp. Eye Res. 84: 378-380, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17109857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17109857</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17109857[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/10.1016/j.exer.2006.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17109857">Mullins et al. (2007)</a> localized the fibulin-5 protein to Bruch membrane and to the intercapillary pillars of the choriocapillaris in normal human donor eyes. In eyes with age-related macular degeneration (ARMD3; <a href="/entry/608895">608895</a>), they localized the protein to pathologic basal deposits beneath the retinal pigment epithelium (RPE) as well as in some small drusen. <a href="#11" class="mim-tip-reference" title="Mullins, R. F., Olvera, M. A., Clark, A. F., Stone, E. M. <strong>Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration.</strong> Exp. Eye Res. 84: 378-380, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17109857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17109857</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17109857[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/10.1016/j.exer.2006.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17109857">Mullins et al. (2007)</a> suggested that fibulin-5 may promote extracellular deposit formation in macular degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17109857" 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="Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. <strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong> J. Biol. Chem. 282: 11805-11816, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>] [<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17324935">Kobayashi et al. (2007)</a> found that mouse Fbln3 and Fbln4 and both mouse and human FBLN5 were secreted into the culture media of transfected HEK293 cells. Solid-phase binding assays showed that these proteins bound differentially to extracellular proteins. Mouse Fbln5 bound to tropoelastin (ELN; <a href="/entry/130160">130160</a>) and weakly to collagen XV (see <a href="/entry/120325">120325</a>)-derived endostatin, but not to fibronectin (<a href="/entry/135600">135600</a>) or most basement membrane proteins examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" 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>Autosomal Recessive Cutis Laxa</em></strong></p><p>
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Hereditary cutis laxa comprises a heterogeneous group of connective tissue disorders characterized by loose skin and variable systemic involvement. The phenotypic abnormalities observed in a fibulin-5 knockout mouse model by <a href="#12" class="mim-tip-reference" title="Nakamura, T., Lozano, P. R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C.-F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross, J., Jr., Honjo, T., Chien, K. R. <strong>Fibulin-5/DANCE is essential for elastogenesis in vivo.</strong> Nature 415: 171-175, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805835</a>] [<a href="https://doi.org/10.1038/415171a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805835">Nakamura et al. (2002)</a> are reminiscent of human autosomal recessive cutis laxa type I (ARCL1A; <a href="/entry/219100">219100</a>). Both share cutis laxa, lung emphysema, and arterial involvement. <a href="#8" class="mim-tip-reference" title="Loeys, B., van Maldergem, L., Mortier, G., Coucke, P., Gerniers, S., Naeyaert, J.-M., de Paepe, A. <strong>Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa.</strong> Hum. Molec. Genet. 11: 2113-2118, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189163</a>] [<a href="https://doi.org/10.1093/hmg/11.18.2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189163">Loeys et al. (2002)</a> studied a large consanguineous Turkish family with 4 patients affected by autosomal recessive cutis laxa type I, originally described by <a href="#17" class="mim-tip-reference" title="Van Maldergem, L., Vamos, E., Liebaers, I., Petit, P., Vandevelde, G., Simonis-Blumenfrucht, A., Bouffioux, R., Kulakowski, S., Hanquinet, S., Van Durme, P., Laporte, M., Ledoux-Corbusier, M. <strong>Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs.</strong> Am. J. Med. Genet. 31: 455-464, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3232707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3232707</a>] [<a href="https://doi.org/10.1002/ajmg.1320310226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3232707">Van Maldergem et al. (1988)</a>, and demonstrated the presence of a homozygous missense mutation in the FBLN5 gene, resulting in a ser227-to-pro (S227P; <a href="#0001">604580.0001</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12189163+11805835+3232707" 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="#5" class="mim-tip-reference" title="Hu, Q., Loeys, B. L., Coucke, P. J., De Paepe, A., Mecham, R. P., Choi, J., Davis, E. C., Urban, Z. <strong>Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa.</strong> Hum. Molec. Genet. 15: 3379-3386, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17035250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17035250</a>] [<a href="https://doi.org/10.1093/hmg/ddl414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17035250">Hu et al. (2006)</a> analyzed 2 disease-causing missense substitutions in fibulin-5, C217R (<a href="#0010">604580.0010</a>) and S227P, and found evidence for misfolding, decreased secretion, and reduced interaction with elastin and fibrillin-1, resulting in impaired elastic fiber development. These findings supported the hypothesis that fibulin-5 is necessary for elastic fiber formation by facilitating the deposition of elastin onto a microfibrillar scaffold via direct molecular interactions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17035250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others. <strong>Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.</strong> Hum. Mutat. 34: 111-121, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22829427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22829427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22829427[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/10.1002/humu.22165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22829427">Callewaert et al. (2013)</a> analyzed the FBLN4 (<a href="/entry/604633">604633</a>), FBLN5, and LTBP4 (<a href="/entry/604710">604710</a>) genes in 12 families with type I ARCL and identified homozygous mutations in the FLBN5 gene in 2 families (<a href="#0010">604580.0010</a> and <a href="#0011">604580.0011</a>). Homozygous or compound heterozygous mutations in LTBP4 were identified in 9 families (see, e.g., <a href="/entry/604710#0005">604710.0005</a>-<a href="/entry/604710#0008">604710.0008</a>). No mutations were found in the FBLN4 gene, and no mutations were detected in 1 family in which the proband had cutis laxa and bladder diverticula without obvious emphysema. <a href="#2" class="mim-tip-reference" title="Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others. <strong>Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.</strong> Hum. Mutat. 34: 111-121, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22829427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22829427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22829427[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/10.1002/humu.22165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22829427">Callewaert et al. (2013)</a> noted that the FBLN5 and LTBP4 mutations caused a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seemed to be more severe in patients with LTBP4 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22829427" 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>Autosomal Dominant Cutis Laxa</em></strong></p><p>
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In a patient with autosomal dominant cutis laxa (ADCL2; <a href="/entry/614434">614434</a>), <a href="#10" class="mim-tip-reference" title="Markova, D., Zou, Y., Ringpfeil, F., Sasaki, T., Kostka, G., Timpl, R., Uitto, J., Chu, M.-L. <strong>Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene.</strong> Am. J. Hum. Genet. 72: 998-1004, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618961</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618961[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/10.1086/373940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618961">Markova et al. (2003)</a> identified a 22-kb tandem duplication in the FBLN5 gene, resulting in a 483-bp duplication (<a href="#0002">604580.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12618961" 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>Age-Related Macular Degeneration 3</em></strong></p><p>
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<a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> studied 402 patients with age-related macular degeneration (ARMD3; <a href="/entry/608895">608895</a>) and identified 7 different mutations in the FBLN5 gene (<a href="#0003">604580.0003</a>-<a href="#0009">604580.0009</a>) that were not found in any of 429 controls (p = 0.006). Each of the 7 patients had small circular drusen, commonly referred to as basal laminar or cuticular drusen. All of the patients were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Lotery, A. J., Baas, D., Ridley, C., Jones, R. P. O., Klaver, C. C. W., Stone, E., Nakamura, T., Luff, A., Griffiths, H., Wang, T., Bergen, A. A. B., Trump, D. <strong>Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa.</strong> Hum. Mutat. 27: 568-574, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16652333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16652333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16652333[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/10.1002/humu.20344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16652333">Lotery et al. (2006)</a> investigated the role of fibulin-5 in ARMD using 2 European cohorts of 805 ARMD patients and 279 controls and by determining the functional effects of the missense mutations on expression of the FBLN5 gene. They found 2 novel sequence changes in ARMD patients that were absent in controls and expressed these and the other 9 previously reported FBLN5 mutations associated with ARMD and 2 associated with autosomal recessive cutis laxa. Fibulin-5 secretion was significantly reduced (p less than 0.001) for 4 ARMD missense mutations and 2 cutis laxa mutations. These results suggested that some missense mutations associated with ARMD lead to decreased fibulin-5 secretion with a possible corresponding reduction in elastinogenesis. The studies further demonstrated that FBLN5 mutations can be associated with different phenotypes of ARMD (not limited to the previously described cuticular drusen type). FBLN5 ARMD can be a cause of choroidal neovascularization in the absence of drusen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16652333" 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>Demyelinating Charcot-Marie-Tooth disease, Type 1H</em></strong></p><p>
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In affected members of 3 families with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; <a href="/entry/619764">619764</a>), <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C. <strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong> Brain 134: 1839-1852, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21576112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21576112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21576112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awr076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21576112">Auer-Grumbach et al. (2011)</a> identified 3 different heterozygous missense mutations in the FBLN5 gene (<a href="#0012">604580.0012</a>-<a href="#0014">604580.0014</a>). Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21576112" 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="#14" class="mim-tip-reference" title="Safka Brozkova, D., Lassuthova, P., Neupauerova, J., Krutova, M., Haberlova, J., Stejskal, D., Seeman, P. <strong>Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth type 1 neuropathy. (Letter)</strong> Brain 136: e232, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23328402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23328402</a>] [<a href="https://doi.org/10.1093/brain/aws333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23328402">Safka Brozkova et al. (2013)</a> identified a heterozygous missense mutation in the FBLN5 gene (R373C; <a href="#0012">604580.0012</a>) in affected members of a Czech family with CMT1H. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23328402" 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 3 affected members spanning 3 generations of a Chinese family with CMT1H, <a href="#3" class="mim-tip-reference" title="Cheng, S., Lv, H., Zhang, W., Wang, Z., Shi, X., Liang, W., Yuan, Y. <strong>Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation.</strong> Clin. Neuropath. 36: 171-177, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28332470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28332470</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28332470[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/10.5414/NP301011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28332470">Cheng et al. (2017)</a> identified a heterozygous R373C mutation (<a href="#0012">604580.0012</a>) in the FBLN5 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28332470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 19 families with CMT1H, some of whom had previously been reported, <a href="#15" class="mim-tip-reference" title="Safka Brozkova, D., Stojkovic, T., Haberlova, J., Mazanec, R., Windhager, R., Fernandes Rosenegger, P., Hacker, S., Zuchner, S., Kochanski, A., Leonard-Louis, S., Francou, B., Latour, P., Senderek, J., Seeman, P., Auer-Grumbach, M. <strong>Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.</strong> Europ. J. Neurol. 27: 2568-2574, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32757322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32757322</a>] [<a href="https://doi.org/10.1111/ene.14463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32757322">Safka Brozkova et al. (2020)</a> identified 3 different heterozygous missense mutations in the FBLN5 gene. R373C (<a href="#0012">604580.0012</a>) was the most common mutation, occurring in 15 families of Austrian, Czech, and French origin. Three families of Czech or German origin carried a heterozygous R331H mutation (<a href="#0015">604580.0015</a>), and 1 French family carried a D329V mutation (<a href="#0016">604580.0016</a>). The mutations, which were detected by Sanger sequencing, multigene panel sequencing, or whole-exome sequencing, segregated with the disorder in families from whom DNA was available for the affected members. Functional studies of the variants were not performed, but they were either absent from or found only once in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32757322" 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="#18" class="mim-tip-reference" title="Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N. <strong>Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.</strong> Nature 415: 168-171, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805834</a>] [<a href="https://doi.org/10.1038/415168a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805834">Yanagisawa et al. (2002)</a> generated mice deficient in fibulin-5 by targeted disruption. Homozygous mutant mice were viable and appeared indistinguishable from wildtype littermates during the first 4 weeks except that slight looseness of the skin was noticeable by weaning. By approximately 50 days of age homozygous mutant mice showed lax skin, which progressed with age. The lungs of homozygous mutant mice were expanded and contained dilated alveoli, which were most severe in peripheral regions. There was tortuosity and elongation of the aorta, as well as elongation of the ductus arteriosus. The ascending aorta proximal to the aortic arch was elongated in fibulin-5 -/- mice, causing the brachiocephalic trunk and left common carotid artery to be juxtaposed. Elastin staining of skin showed a marked reduction of the elastic fiber network surrounding hair follicles. Enlargement of the distal airspaces of the lung was evident by 2 weeks of age in homozygous mutant mice. This phenotype progressed with age, leading to a severe emphysematous change with the formation of peripheral bullae in adult mice. Elastin staining showed that elastin (<a href="/entry/130160">130160</a>) at the tips of the secondary septae was fragmented and that the elastic fibers associated with the alveolar walls were short, thickened, and disrupted in 2-week-old homozygous mice when compared with wildtype littermates. Elastin staining of the aorta showed that elastic laminae in homozygous mutant mice were fragmented, the defect being more severe toward the adventitia. Despite the disorganized elastic laminae, there was no indication of aneurysms or dissections of the medial layers of aortae in fibulin-5 -/- mice. Other organs were normal. Disruption of the elastic laminae of vessels was evident as early as postnatal day 1, suggesting that the defect seen in the adult aorta of homozygous mutant mice was not the result of degradation of intact elastic laminae by activated inflammatory cells, but rather the consequence of an underlying developmental defect in the final organization of the elastic fibers in fibulin-5 -/- mice. <a href="#18" class="mim-tip-reference" title="Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N. <strong>Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.</strong> Nature 415: 168-171, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805834</a>] [<a href="https://doi.org/10.1038/415168a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805834">Yanagisawa et al. (2002)</a> performed solid-phase binding assays to assess the biochemical interaction of fibulin-5 with other extracellular matrix proteins. Fibulin-5 bound strongly to tropoelastin, and this binding was completely inhibited in the presence of EDTA, suggesting that fibulin-5 may use calcium-binding EGF-like motifs to bind to tropoelastin. Using immunogold labeling and electron microscopy, <a href="#18" class="mim-tip-reference" title="Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N. <strong>Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.</strong> Nature 415: 168-171, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805834</a>] [<a href="https://doi.org/10.1038/415168a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805834">Yanagisawa et al. (2002)</a> demonstrated that fibulin-5 protein is present along the surface of elastic lamina adjacent to the endothelial cell membrane, demonstrating that fibulin-5 is a surface component of elastic fibers in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11805834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Nakamura, T., Lozano, P. R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C.-F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross, J., Jr., Honjo, T., Chien, K. R. <strong>Fibulin-5/DANCE is essential for elastogenesis in vivo.</strong> Nature 415: 171-175, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805835</a>] [<a href="https://doi.org/10.1038/415171a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805835">Nakamura et al. (2002)</a> independently generated fibulin-5 -/- mice. The phenotypic findings were similar to those described by <a href="#18" class="mim-tip-reference" title="Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N. <strong>Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.</strong> Nature 415: 168-171, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805834</a>] [<a href="https://doi.org/10.1038/415168a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805834">Yanagisawa et al. (2002)</a>. They showed that the aorta, lung, and skin of fibulin-5 -/- mice contained fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibers. Fibulin-5 interacts directly with elastic fibers in vitro, and serves as a ligand for cell surface integrins alpha-5/beta-3, alpha-5/beta-5 (see <a href="/entry/193210">193210</a>), and alpha-9/beta-1 (see <a href="/entry/603963">603963</a>) through its N-terminal domain. <a href="#12" class="mim-tip-reference" title="Nakamura, T., Lozano, P. R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C.-F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross, J., Jr., Honjo, T., Chien, K. R. <strong>Fibulin-5/DANCE is essential for elastogenesis in vivo.</strong> Nature 415: 171-175, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805835</a>] [<a href="https://doi.org/10.1038/415171a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805835">Nakamura et al. (2002)</a> postulated that fibulin-5 may provide anchorage of elastic fibers to cells, thereby acting to stabilize and organize elastic fibers in the skin, lung, and vasculature. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11805835+11805834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>16 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604580[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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IA</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">rs28939370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939370;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=rs28939370" 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=rs28939370" 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="Loeys, B., van Maldergem, L., Mortier, G., Coucke, P., Gerniers, S., Naeyaert, J.-M., de Paepe, A. <strong>Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa.</strong> Hum. Molec. Genet. 11: 2113-2118, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189163</a>] [<a href="https://doi.org/10.1093/hmg/11.18.2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189163">Loeys et al. (2002)</a> studied a large consanguineous Turkish family, originally described by <a href="#17" class="mim-tip-reference" title="Van Maldergem, L., Vamos, E., Liebaers, I., Petit, P., Vandevelde, G., Simonis-Blumenfrucht, A., Bouffioux, R., Kulakowski, S., Hanquinet, S., Van Durme, P., Laporte, M., Ledoux-Corbusier, M. <strong>Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs.</strong> Am. J. Med. Genet. 31: 455-464, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3232707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3232707</a>] [<a href="https://doi.org/10.1002/ajmg.1320310226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3232707">Van Maldergem et al. (1988)</a>, in which 4 patients were affected by autosomal recessive cutis laxa type I (ARCL1A; <a href="/entry/219100">219100</a>) and demonstrated homozygosity for a 998T-C transition in the FBLN5 gene. The mutation was predicted to result in a ser227-to-pro (S227P) substitution in the fourth cbEGF-like domain of fibulin-5 protein. Because serine is found in this position in mouse and rat fibulin-5 as well as in human fibulin-3, substitution for this amino acid may have important structural and functional consequences for normal elastogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12189163+3232707" 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="#5" class="mim-tip-reference" title="Hu, Q., Loeys, B. L., Coucke, P. J., De Paepe, A., Mecham, R. P., Choi, J., Davis, E. C., Urban, Z. <strong>Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa.</strong> Hum. Molec. Genet. 15: 3379-3386, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17035250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17035250</a>] [<a href="https://doi.org/10.1093/hmg/ddl414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17035250">Hu et al. (2006)</a> showed that S227P mutant fibulin-5 is synthesized and secreted at a reduced rate compared to wildtype. The mutant also failed to be incorporated into elastic fibers by transfected rat lung fibroblasts. Purified recombinant S227P fibulin-5 showed reduced affinity for tropoelastin in solid-phase binding assays as well as impaired association with fibrillin-1 microfibrils; in addition, the mutant protein triggered an endoplasmic reticulum (ER) stress response, as indicated by strong colocalization of the mutant with folding chaperones in the ER and by increased rates of apoptosis in patient fibroblasts. Histologic analysis of patient skin sections showed a lack of fibulin-5 in the extracellular matrix and concomitant disorganization of dermal elastic fibers, and electron microscopy of patient elastic fibers showed a failure of elastin globules to fuse into a continuous elastic fiber core. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17035250" 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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005810" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005810" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005810</a>
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<p><a href="#10" class="mim-tip-reference" title="Markova, D., Zou, Y., Ringpfeil, F., Sasaki, T., Kostka, G., Timpl, R., Uitto, J., Chu, M.-L. <strong>Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene.</strong> Am. J. Hum. Genet. 72: 998-1004, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618961</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618961[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/10.1086/373940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618961">Markova et al. (2003)</a> analyzed the expression of the elastin gene and the fibulin genes 1 through 5 in fibroblasts from 5 patients with cutis laxa (ADCL2; <a href="/entry/614434">614434</a>). One patient was found to express both normal (2.2 kb) and mutant (2.7 kb) fibulin-5 mRNA transcripts. The larger transcript contained an internal duplication of 483 nucleotides, which resulted in the synthesis and secretion of a mutant fibulin-5 protein with 4 additional tandem calcium-binding epidermal growth factor-like motifs. The mutation arose from a 22-kb tandem gene duplication, encompassing the sequence from intron 4 to exon 9. No fibulin-5 or elastin mutations were detected in the other 4 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12618961" 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 MACULAR DEGENERATION, AGE-RELATED, 3</strong>
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FBLN5, VAL60LEU
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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> rs121434299 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434299;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/rs121434299?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=rs121434299" 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=rs121434299" 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=RCV000005811 OR RCV001851678 OR RCV003447069 OR RCV004751203" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005811, RCV001851678, RCV003447069, RCV004751203" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005811...</a>
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.178G-C transversion in the FBLN5 gene, resulting in a val60-to-leu (V60L) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" 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> rs121434300 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434300;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/rs121434300?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=rs121434300" 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=rs121434300" 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=RCV000005812 OR RCV001851679 OR RCV003447070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005812, RCV001851679, RCV003447070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005812...</a>
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.212G-A transition in the FBLN5 gene, resulting in an arg71-to-gln (R71Q) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" 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>.0005 MACULAR DEGENERATION, AGE-RELATED, 3</strong>
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FBLN5, PRO87SER
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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> rs121434301 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434301;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/rs121434301?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=rs121434301" 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=rs121434301" 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=RCV000005813 OR RCV003447071" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005813, RCV003447071" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005813...</a>
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.259C-T transition in the FBLN5 gene, resulting in a pro87-to-ser (P87S) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" 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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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 MACULAR DEGENERATION, AGE-RELATED, 3</strong>
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</h4>
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FBLN5, ILE169THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28939072 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939072;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=rs28939072" 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=rs28939072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005814 OR RCV003447072" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005814, RCV003447072" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005814...</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.506T-C transition in the FBLN5 gene, resulting in an ile169-to-thr (I169T) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" 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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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 MACULAR DEGENERATION, AGE-RELATED, 3</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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FBLN5, ARG351TRP
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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> rs28939073 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939073;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/rs28939073?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=rs28939073" 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=rs28939073" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005815 OR RCV001119789 OR RCV001577844 OR RCV002251883 OR RCV002490323 OR RCV003447073 OR RCV004700191" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005815, RCV001119789, RCV001577844, RCV002251883, RCV002490323, RCV003447073, RCV004700191" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005815...</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.1051C-T transition in the FBLN5 gene, resulting in an arg351-to-trp (R351W) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" 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>
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<div>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 MACULAR DEGENERATION, AGE-RELATED, 3</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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<div style="float: left;">
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FBLN5, ALA363THR
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</div>
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</span>
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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> rs121434302 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434302;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/rs121434302?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=rs121434302" 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=rs121434302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005816 OR RCV001851680 OR RCV003447074" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005816, RCV001851680, RCV003447074" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005816...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.1087G-A transition in the FBLN5 gene, resulting in an ala363-to-thr (A363T) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</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="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 MACULAR DEGENERATION, AGE-RELATED, 3</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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<div style="float: left;">
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FBLN5, GLY412GLU
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434303 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434303;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=rs121434303" 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=rs121434303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005817 OR RCV002512815 OR RCV003447075" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005817, RCV002512815, RCV003447075" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005817...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; <a href="/entry/608895">608895</a>), <a href="#16" class="mim-tip-reference" title="Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., Sheffield, V. C. <strong>Missense variations in the fibulin 5 gene and age-related macular degeneration.</strong> New Eng. J. Med. 351: 346-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15269314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15269314</a>] [<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15269314">Stone et al. (2004)</a> identified a heterozygous c.1235G-A transition in the FBLN5 gene, resulting in a gly412-to-glu (G412E) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269314" 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">rs80338766 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338766;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=rs80338766" 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=rs80338766" 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=RCV000020642 OR RCV003447089" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020642, RCV003447089" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020642...</a>
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<p>In 3 affected sibs from a consanguineous Lebanese family with severe generalized cutis laxa (ARCL1A; <a href="/entry/219100">219100</a>), <a href="#2" class="mim-tip-reference" title="Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others. <strong>Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.</strong> Hum. Mutat. 34: 111-121, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22829427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22829427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22829427[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/10.1002/humu.22165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22829427">Callewaert et al. (2013)</a> identified homozygosity for a 649T-C transition in the FBLN5 gene, resulting in a cys217-to-arg (C217R) substitution at a highly conserved residue in the fourth calcium-binding EGF-like domain. The female proband died of pulmonary emphysema and bronchiolitis at 11 months of age; her 2 affected brothers had milder pulmonary emphysema. Other features in the 3 sibs included peripheral pulmonary artery stenosis, aortic valve stenosis and/or insufficiency, pyloric stenosis, and inguinal hernias. <a href="#2" class="mim-tip-reference" title="Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others. <strong>Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.</strong> Hum. Mutat. 34: 111-121, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22829427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22829427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22829427[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/10.1002/humu.22165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22829427">Callewaert et al. (2013)</a> noted that the C217R had previously been identified by <a href="#4" class="mim-tip-reference" title="Claus, S., Fischer, J., Megarbane, H., Megarbane, A., Jobard, F., Debret, R., Peyrol, S., Saker, S., Devillers, M., Sommer, P., Damour, O. <strong>A p.C217R mutation in fibulin-5 from cutis laxa patients is associated with incomplete extracellular matrix formation in a skin equivalent model.</strong> J. Invest. Derm. 128: 1442-1450, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18185537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18185537</a>] [<a href="https://doi.org/10.1038/sj.jid.5701211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18185537">Claus et al. (2008)</a> in another Lebanese family with cutis laxa. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18185537+22829427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 19-month-old girl from a consanguineous Algerian family with severe generalized cutis laxa with facial involvement (ARCL1A; <a href="/entry/219100">219100</a>), <a href="#2" class="mim-tip-reference" title="Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others. <strong>Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.</strong> Hum. Mutat. 34: 111-121, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22829427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22829427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22829427[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/10.1002/humu.22165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22829427">Callewaert et al. (2013)</a> identified homozygosity for a 1171G-T transversion in the FBLN5 gene, resulting in a glu391-to-ter (E391X) substitution in the FBLN-specific domain. The mutation was present in heterozygosity in the unaffected parents and an unaffected sister. The mother had had 2 spontaneous abortions and 2 older sisters and a brother with cutis laxa had died in infancy. The proband had a high and broad forehead, low and broad nasal bridge, beaked nose, large dysplastic ears, sagging cheeks, and everted lower lip. Other features included severe emphysema, normal cardiac status by echocardiography, photophobia, hypotonicity, and normal mental status. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22829427" 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">rs864309526 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs864309526;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=rs864309526" 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=rs864309526" 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=RCV000756132 OR RCV001843302 OR RCV003447124" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000756132, RCV001843302, RCV003447124" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000756132...</a>
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<p>In affected members of a large Austrian kindred (families A and B) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; <a href="/entry/619764">619764</a>), <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C. <strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong> Brain 134: 1839-1852, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21576112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21576112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21576112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awr076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21576112">Auer-Grumbach et al. (2011)</a>, identified a heterozygous c.1117C-T transition (c.1117C-T, NM_006329.3) in exon 10 of the FBLN5 gene, resulting in an arg373-to-cys (R373C) substitution at a highly conserved residue in the fibulin-type C terminus. The mutation, which was found by analysis of protein coding genes within a region identified through linkage analysis, segregated with the disorder in the family and was not found in 317 control individuals or in the 1000 Genomes Project database. Functional studies of the variant were not performed. Nerve and muscle biopsy of 1 patient (B5) showed no obvious changes in the immunohistochemical staining patterns of FBLN5 and elastin, but skin biopsy from another patient (B9) showed mild changes in the structure and arrangement of FBLN5 and elastin; neither of these patients had clinical skin abnormalities or ARMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21576112" 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="#14" class="mim-tip-reference" title="Safka Brozkova, D., Lassuthova, P., Neupauerova, J., Krutova, M., Haberlova, J., Stejskal, D., Seeman, P. <strong>Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth type 1 neuropathy. (Letter)</strong> Brain 136: e232, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23328402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23328402</a>] [<a href="https://doi.org/10.1093/brain/aws333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23328402">Safka Brozkova et al. (2013)</a> identified a heterozygous R373C mutation in affected members of a Czech family with CMT1H. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in the dbSNP (build 132) or Exome Variant Server databases. Functional studies of the variant were not performed. Haplotype analysis indicated that the mutation occurred independently from that in the family reported by <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C. <strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong> Brain 134: 1839-1852, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21576112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21576112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21576112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awr076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21576112">Auer-Grumbach et al. (2011)</a>. None of the Czech patients had ARMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21576112+23328402" 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 3 affected members spanning 3 generations of a Chinese family with CMT1H, <a href="#3" class="mim-tip-reference" title="Cheng, S., Lv, H., Zhang, W., Wang, Z., Shi, X., Liang, W., Yuan, Y. <strong>Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation.</strong> Clin. Neuropath. 36: 171-177, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28332470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28332470</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28332470[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/10.5414/NP301011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28332470">Cheng et al. (2017)</a> identified a heterozygous R373C mutation in the FBLN5 gene. The mutation, which was found by targeted next-generation sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, with evidence of variable expressivity and age-dependent penetrance. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28332470" 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="#15" class="mim-tip-reference" title="Safka Brozkova, D., Stojkovic, T., Haberlova, J., Mazanec, R., Windhager, R., Fernandes Rosenegger, P., Hacker, S., Zuchner, S., Kochanski, A., Leonard-Louis, S., Francou, B., Latour, P., Senderek, J., Seeman, P., Auer-Grumbach, M. <strong>Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.</strong> Europ. J. Neurol. 27: 2568-2574, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32757322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32757322</a>] [<a href="https://doi.org/10.1111/ene.14463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32757322">Safka Brozkova et al. (2020)</a> identified a heterozygous R373C mutation in the FBLN5 gene in affected members of 15 unrelated families from Austria, the Czech Republic, and France with CMT1H. The mutation, which was found by exome sequencing and segregated with the disorder in the families, was not present in the gnomAD database. Haplotype analysis indicated that some of the Czech families shared a similar haplotype, although others had independent mutational events. Functional studies of the variant were not performed. Three of the families had previously been reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32757322" 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 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs144288844 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs144288844;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/rs144288844?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=rs144288844" 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=rs144288844" 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=RCV000202614 OR RCV000521928 OR RCV001121879 OR RCV001249315 OR RCV001843303 OR RCV003447125 OR RCV004816351 OR RCV004816352" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000202614, RCV000521928, RCV001121879, RCV001249315, RCV001843303, RCV003447125, RCV004816351, RCV004816352" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000202614...</a>
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<p>In 5 affected members of a family (family C) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; <a href="/entry/619764">619764</a>), <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C. <strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong> Brain 134: 1839-1852, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21576112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21576112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21576112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awr076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21576112">Auer-Grumbach et al. (2011)</a> identified a heterozygous c.268G-A transition (c.268G-A, NM_006329.3) in exon 4 of the FBLN5 gene, resulting in a gly90-to-ser (G90S) substitution. The variant was not found in the 1000 Genomes Project database, in 517 control individuals, or in previous studies of 1,204 patients with ARMD or 766 control individuals. Two patients, 1 severely affected and 1 clinically asymptomatic, also carried a heterozygous A339T variant in the YARS gene (<a href="/entry/603623">603623</a>), but this variant did not segregate with the peripheral neuropathy in this family. Three affected family members had hyperelastic skin and 1 had ARMD. Functional studies of the variant were not performed. Skin biopsies from 2 patients with hyperelastic skin showed a marked increase in FBLN5 immunoreactivity, which was present as short plump fibers. An unrelated individual with sporadic occurrence of the disorder was also found to carry the G90S mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21576112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0014 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
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FBLN5, VAL126MET (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61734479;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs61734479</a>)
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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> rs61734479 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61734479;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/rs61734479?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=rs61734479" 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=rs61734479" 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=RCV000202603 OR RCV000405354 OR RCV000584853 OR RCV001843304 OR RCV003917823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000202603, RCV000405354, RCV000584853, RCV001843304, RCV003917823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000202603...</a>
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<p>In 2 members of a family (family D) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; <a href="/entry/619764">619764</a>), <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C. <strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong> Brain 134: 1839-1852, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21576112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21576112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21576112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awr076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21576112">Auer-Grumbach et al. (2011)</a> identified a heterozygous c.376G-A transition (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61734479;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs61734479</a>) in the FBLN5 gene, resulting in a val126-to-met (V126M) substitution at a conserved residue. The variant was also found in 2 of 317 supposed controls, both of whom were found to have peripheral neuropathy, as well as in 2 of 300 patients with age-related macular degeneration, 1 of whom had evidence of a peripheral neuropathy (patient data from Table 1). Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21576112" 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>.0015 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
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FBLN5, ARG331HIS
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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> rs774735234 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs774735234;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/rs774735234?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=rs774735234" 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=rs774735234" 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=RCV001843340 OR RCV002034713 OR RCV002290773" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001843340, RCV002034713, RCV002290773" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001843340...</a>
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<p>In 4 patients from 3 unrelated families of Czech and German origin (CZ7, CZ8, and GE1) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; <a href="/entry/619764">619764</a>), <a href="#15" class="mim-tip-reference" title="Safka Brozkova, D., Stojkovic, T., Haberlova, J., Mazanec, R., Windhager, R., Fernandes Rosenegger, P., Hacker, S., Zuchner, S., Kochanski, A., Leonard-Louis, S., Francou, B., Latour, P., Senderek, J., Seeman, P., Auer-Grumbach, M. <strong>Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.</strong> Europ. J. Neurol. 27: 2568-2574, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32757322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32757322</a>] [<a href="https://doi.org/10.1111/ene.14463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32757322">Safka Brozkova et al. (2020)</a> identified a heterozygous c.992G-A transition (c.992G-A, NM_006329.3) in the FBLN5 gene, resulting in an arg331-to-his (R331H) substitution at a highly conserved residue in the C-terminal domain. The mutation was present once in the gnomAD database. Segregation with the disorder was demonstrated in family CZ7. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32757322" 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> rs1172268284 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1172268284;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/rs1172268284?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=rs1172268284" 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=rs1172268284" 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=RCV001843339" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001843339" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001843339</a>
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<p>In a French parent and offspring (family FR2) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; <a href="/entry/619764">619764</a>), <a href="#15" class="mim-tip-reference" title="Safka Brozkova, D., Stojkovic, T., Haberlova, J., Mazanec, R., Windhager, R., Fernandes Rosenegger, P., Hacker, S., Zuchner, S., Kochanski, A., Leonard-Louis, S., Francou, B., Latour, P., Senderek, J., Seeman, P., Auer-Grumbach, M. <strong>Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.</strong> Europ. J. Neurol. 27: 2568-2574, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32757322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32757322</a>] [<a href="https://doi.org/10.1111/ene.14463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32757322">Safka Brozkova et al. (2020)</a> identified a heterozygous c.986A-T transversion (c.986A-T, NM_006329.3) in the FBLN5 gene, resulting in an asp329-to-val (D329V) substitution at a highly conserved residue in the C-terminal domain. The mutation, which was found by exome sequencing, was present once in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32757322" 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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Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C.
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<strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong>
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Brain 134: 1839-1852, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21576112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21576112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21576112[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=21576112" 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/brain/awr076" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.22165" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.5414/NP301011" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/sj.jid.5701211" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl414" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000015382" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/11.18.2113" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20344" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/373940" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.exer.2006.09.021" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/415171a" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.274.32.22476" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa040833" target="_blank">Full Text</a>]
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</div>
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<a id="17" class="mim-anchor"></a>
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<a id="Van Maldergem1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Van Maldergem, L., Vamos, E., Liebaers, I., Petit, P., Vandevelde, G., Simonis-Blumenfrucht, A., Bouffioux, R., Kulakowski, S., Hanquinet, S., Van Durme, P., Laporte, M., Ledoux-Corbusier, M.
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<strong>Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs.</strong>
|
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Am. J. Med. Genet. 31: 455-464, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3232707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3232707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3232707" 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.1320310226" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Yanagisawa2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N.
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<strong>Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.</strong>
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Nature 415: 168-171, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805834</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11805834" 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/10.1038/415168a" target="_blank">Full Text</a>]
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</p>
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</ol>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 02/24/2022
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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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Cassandra L. Kniffin - updated : 12/10/2015<br>Patricia A. Hartz - updated : 11/4/2013<br>Patricia A. Hartz - updated : 11/4/2013<br>Marla J. F. O'Neill - updated : 2/14/2013<br>Marla J. F. O'Neill - updated : 2/13/2013<br>Jane Kelly - updated : 10/19/2007<br>Victor A. McKusick - updated : 7/12/2006<br>Marla J. F. O'Neill - updated : 8/11/2004<br>Victor A. McKusick - updated : 4/10/2003<br>George E. Tiller - updated : 12/10/2002<br>Ada Hamosh - updated : 1/11/2002<br>Carol A. Bocchini - updated : 2/15/2001
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</span>
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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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Paul J. Converse : 2/19/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 03/02/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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ckniffin : 02/24/2022<br>carol : 09/26/2019<br>carol : 03/02/2017<br>carol : 02/28/2017<br>carol : 12/21/2015<br>ckniffin : 12/10/2015<br>mgross : 12/9/2013<br>mcolton : 11/4/2013<br>mcolton : 11/4/2013<br>tpirozzi : 7/2/2013<br>carol : 2/15/2013<br>terry : 2/14/2013<br>terry : 2/13/2013<br>terry : 1/30/2013<br>terry : 6/11/2012<br>carol : 2/27/2012<br>alopez : 1/26/2012<br>carol : 10/19/2007<br>carol : 10/16/2007<br>alopez : 7/19/2006<br>terry : 7/12/2006<br>alopez : 8/10/2005<br>carol : 9/2/2004<br>terry : 9/1/2004<br>carol : 8/11/2004<br>terry : 8/11/2004<br>tkritzer : 4/16/2003<br>terry : 4/10/2003<br>cwells : 12/10/2002<br>alopez : 1/18/2002<br>terry : 1/11/2002<br>mcapotos : 2/16/2001<br>carol : 2/15/2001<br>carol : 2/21/2000
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</span>
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</div>
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</div>
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</div>
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</div>
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<div 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> 604580
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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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FIBULIN 5; FBLN5
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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DEVELOPMENTAL ARTERIES AND NEURAL CREST EGF-LIKE; DANCE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: FBLN5</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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<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: 14q32.12
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:91,869,411-91,947,694 </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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<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-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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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="4">
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<span class="mim-font">
|
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14q32.12
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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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?Cutis laxa, autosomal dominant 2
|
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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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614434
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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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<tr>
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<td>
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<span class="mim-font">
|
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Charcot-Marie-Tooth disease, demyelinating, type 1H
|
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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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619764
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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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<tr>
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<td>
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<span class="mim-font">
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Cutis laxa, autosomal recessive, type IA
|
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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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219100
|
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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 recessive
|
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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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<tr>
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<td>
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<span class="mim-font">
|
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Macular degeneration, age-related, 3
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
608895
|
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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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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
|
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|
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Members of the fibulin family of proteins, like FBLN5, are extracellular matrix proteins characterized by tandem arrays of EGF (131530)-like domains and a C-terminal fibulin (see FBLN1; 135820)-type module (Kobayashi et al., 2007). </p>
|
|
</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">
|
|
<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">
|
|
<p>Using a cDNA probe derived from signal sequence trap screening of mouse embryonic heart, EST database screening, and 5-prime RACE, Nakamura et al. (1999) obtained a cDNA for fibulin-5 (FBLN5), which they called DANCE (for developmental arteries and neural crest EGF-like). The FBLN5 cDNA encodes a deduced 448-amino acid secreted protein with a molecular mass of 66 kD. Its amino acid sequence is 94% identical to that of the mouse Fbln5 protein. It contains 6 calcium-binding EGF-like domains, one of which contains an RGD motif. Northern blot analysis revealed a major transcript of 2.6 kb that is expressed predominantly in heart, ovary, and colon but also in kidney, pancreas, testis, lung, and placenta. FBLN5 is not detectable in brain, liver, thymus, prostate, or peripheral blood leukocytes. FBLN5 is prominently expressed in developing arteries; in adult vessels, its expression is largely diminished but is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells. </p><p>Using radioimmunoassays, Kobayashi et al. (2007) found variable Fbln5 expression in all 14 mouse tissues examined, with highest expression in aorta and lung, and lowest expression in kidney, brain, and thymus. Immunohistochemical analysis localized Fbln5 in perichondrium of developing bone in day-15 mouse embryos and in blood vessel wall, basement membrane, and parabronchial area of the large airway in day-14 mouse embryos. Electron microscopy after rotary shadowing revealed that recombinant mouse Fbln5, like Fbln3 (EFEMP1; 601548) and Fbln4 (604633), appeared as a 20-nm rod with a globular domain at one end, which represented the N-terminal EGF modules. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By FISH, Nakamura et al. (1999) mapped the FBLN5 gene to chromosome 14q32.1. By FISH and radiation hybrid analysis, Kowal et al. (1999) mapped the FBLN5 gene to 14q31. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Nakamura et al. (1999) showed that FBLN5 promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. The authors suggested that FBLN5 is a novel vascular ligand for integrin receptors and may play a role in vascular development and remodeling. </p><p>Mullins et al. (2007) localized the fibulin-5 protein to Bruch membrane and to the intercapillary pillars of the choriocapillaris in normal human donor eyes. In eyes with age-related macular degeneration (ARMD3; 608895), they localized the protein to pathologic basal deposits beneath the retinal pigment epithelium (RPE) as well as in some small drusen. Mullins et al. (2007) suggested that fibulin-5 may promote extracellular deposit formation in macular degeneration. </p><p>Kobayashi et al. (2007) found that mouse Fbln3 and Fbln4 and both mouse and human FBLN5 were secreted into the culture media of transfected HEK293 cells. Solid-phase binding assays showed that these proteins bound differentially to extracellular proteins. Mouse Fbln5 bound to tropoelastin (ELN; 130160) and weakly to collagen XV (see 120325)-derived endostatin, but not to fibronectin (135600) or most basement membrane proteins examined. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
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</div>
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|
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<span class="mim-text-font">
|
|
<p><strong><em>Autosomal Recessive Cutis Laxa</em></strong></p><p>
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|
Hereditary cutis laxa comprises a heterogeneous group of connective tissue disorders characterized by loose skin and variable systemic involvement. The phenotypic abnormalities observed in a fibulin-5 knockout mouse model by Nakamura et al. (2002) are reminiscent of human autosomal recessive cutis laxa type I (ARCL1A; 219100). Both share cutis laxa, lung emphysema, and arterial involvement. Loeys et al. (2002) studied a large consanguineous Turkish family with 4 patients affected by autosomal recessive cutis laxa type I, originally described by Van Maldergem et al. (1988), and demonstrated the presence of a homozygous missense mutation in the FBLN5 gene, resulting in a ser227-to-pro (S227P; 604580.0001) substitution. </p><p>Hu et al. (2006) analyzed 2 disease-causing missense substitutions in fibulin-5, C217R (604580.0010) and S227P, and found evidence for misfolding, decreased secretion, and reduced interaction with elastin and fibrillin-1, resulting in impaired elastic fiber development. These findings supported the hypothesis that fibulin-5 is necessary for elastic fiber formation by facilitating the deposition of elastin onto a microfibrillar scaffold via direct molecular interactions. </p><p>Callewaert et al. (2013) analyzed the FBLN4 (604633), FBLN5, and LTBP4 (604710) genes in 12 families with type I ARCL and identified homozygous mutations in the FLBN5 gene in 2 families (604580.0010 and 604580.0011). Homozygous or compound heterozygous mutations in LTBP4 were identified in 9 families (see, e.g., 604710.0005-604710.0008). No mutations were found in the FBLN4 gene, and no mutations were detected in 1 family in which the proband had cutis laxa and bladder diverticula without obvious emphysema. Callewaert et al. (2013) noted that the FBLN5 and LTBP4 mutations caused a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seemed to be more severe in patients with LTBP4 mutations. </p><p><strong><em>Autosomal Dominant Cutis Laxa</em></strong></p><p>
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In a patient with autosomal dominant cutis laxa (ADCL2; 614434), Markova et al. (2003) identified a 22-kb tandem duplication in the FBLN5 gene, resulting in a 483-bp duplication (604580.0002). </p><p><strong><em>Age-Related Macular Degeneration 3</em></strong></p><p>
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Stone et al. (2004) studied 402 patients with age-related macular degeneration (ARMD3; 608895) and identified 7 different mutations in the FBLN5 gene (604580.0003-604580.0009) that were not found in any of 429 controls (p = 0.006). Each of the 7 patients had small circular drusen, commonly referred to as basal laminar or cuticular drusen. All of the patients were examined in a retina clinic. </p><p>Lotery et al. (2006) investigated the role of fibulin-5 in ARMD using 2 European cohorts of 805 ARMD patients and 279 controls and by determining the functional effects of the missense mutations on expression of the FBLN5 gene. They found 2 novel sequence changes in ARMD patients that were absent in controls and expressed these and the other 9 previously reported FBLN5 mutations associated with ARMD and 2 associated with autosomal recessive cutis laxa. Fibulin-5 secretion was significantly reduced (p less than 0.001) for 4 ARMD missense mutations and 2 cutis laxa mutations. These results suggested that some missense mutations associated with ARMD lead to decreased fibulin-5 secretion with a possible corresponding reduction in elastinogenesis. The studies further demonstrated that FBLN5 mutations can be associated with different phenotypes of ARMD (not limited to the previously described cuticular drusen type). FBLN5 ARMD can be a cause of choroidal neovascularization in the absence of drusen. </p><p><strong><em>Demyelinating Charcot-Marie-Tooth disease, Type 1H</em></strong></p><p>
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In affected members of 3 families with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011) identified 3 different heterozygous missense mutations in the FBLN5 gene (604580.0012-604580.0014). Functional studies of the variants were not performed. </p><p>Safka Brozkova et al. (2013) identified a heterozygous missense mutation in the FBLN5 gene (R373C; 604580.0012) in affected members of a Czech family with CMT1H. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. </p><p>In 3 affected members spanning 3 generations of a Chinese family with CMT1H, Cheng et al. (2017) identified a heterozygous R373C mutation (604580.0012) in the FBLN5 gene. </p><p>In affected members of 19 families with CMT1H, some of whom had previously been reported, Safka Brozkova et al. (2020) identified 3 different heterozygous missense mutations in the FBLN5 gene. R373C (604580.0012) was the most common mutation, occurring in 15 families of Austrian, Czech, and French origin. Three families of Czech or German origin carried a heterozygous R331H mutation (604580.0015), and 1 French family carried a D329V mutation (604580.0016). The mutations, which were detected by Sanger sequencing, multigene panel sequencing, or whole-exome sequencing, segregated with the disorder in families from whom DNA was available for the affected members. Functional studies of the variants were not performed, but they were either absent from or found only once in the gnomAD database. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</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>Yanagisawa et al. (2002) generated mice deficient in fibulin-5 by targeted disruption. Homozygous mutant mice were viable and appeared indistinguishable from wildtype littermates during the first 4 weeks except that slight looseness of the skin was noticeable by weaning. By approximately 50 days of age homozygous mutant mice showed lax skin, which progressed with age. The lungs of homozygous mutant mice were expanded and contained dilated alveoli, which were most severe in peripheral regions. There was tortuosity and elongation of the aorta, as well as elongation of the ductus arteriosus. The ascending aorta proximal to the aortic arch was elongated in fibulin-5 -/- mice, causing the brachiocephalic trunk and left common carotid artery to be juxtaposed. Elastin staining of skin showed a marked reduction of the elastic fiber network surrounding hair follicles. Enlargement of the distal airspaces of the lung was evident by 2 weeks of age in homozygous mutant mice. This phenotype progressed with age, leading to a severe emphysematous change with the formation of peripheral bullae in adult mice. Elastin staining showed that elastin (130160) at the tips of the secondary septae was fragmented and that the elastic fibers associated with the alveolar walls were short, thickened, and disrupted in 2-week-old homozygous mice when compared with wildtype littermates. Elastin staining of the aorta showed that elastic laminae in homozygous mutant mice were fragmented, the defect being more severe toward the adventitia. Despite the disorganized elastic laminae, there was no indication of aneurysms or dissections of the medial layers of aortae in fibulin-5 -/- mice. Other organs were normal. Disruption of the elastic laminae of vessels was evident as early as postnatal day 1, suggesting that the defect seen in the adult aorta of homozygous mutant mice was not the result of degradation of intact elastic laminae by activated inflammatory cells, but rather the consequence of an underlying developmental defect in the final organization of the elastic fibers in fibulin-5 -/- mice. Yanagisawa et al. (2002) performed solid-phase binding assays to assess the biochemical interaction of fibulin-5 with other extracellular matrix proteins. Fibulin-5 bound strongly to tropoelastin, and this binding was completely inhibited in the presence of EDTA, suggesting that fibulin-5 may use calcium-binding EGF-like motifs to bind to tropoelastin. Using immunogold labeling and electron microscopy, Yanagisawa et al. (2002) demonstrated that fibulin-5 protein is present along the surface of elastic lamina adjacent to the endothelial cell membrane, demonstrating that fibulin-5 is a surface component of elastic fibers in vivo. </p><p>Nakamura et al. (2002) independently generated fibulin-5 -/- mice. The phenotypic findings were similar to those described by Yanagisawa et al. (2002). They showed that the aorta, lung, and skin of fibulin-5 -/- mice contained fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibers. Fibulin-5 interacts directly with elastic fibers in vitro, and serves as a ligand for cell surface integrins alpha-5/beta-3, alpha-5/beta-5 (see 193210), and alpha-9/beta-1 (see 603963) through its N-terminal domain. Nakamura et al. (2002) postulated that fibulin-5 may provide anchorage of elastic fibers to cells, thereby acting to stabilize and organize elastic fibers in the skin, lung, and vasculature. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>16 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IA</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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FBLN5, SER227PRO
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<br />
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SNP: rs28939370,
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ClinVar: RCV000005809, RCV003447068
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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>Loeys et al. (2002) studied a large consanguineous Turkish family, originally described by Van Maldergem et al. (1988), in which 4 patients were affected by autosomal recessive cutis laxa type I (ARCL1A; 219100) and demonstrated homozygosity for a 998T-C transition in the FBLN5 gene. The mutation was predicted to result in a ser227-to-pro (S227P) substitution in the fourth cbEGF-like domain of fibulin-5 protein. Because serine is found in this position in mouse and rat fibulin-5 as well as in human fibulin-3, substitution for this amino acid may have important structural and functional consequences for normal elastogenesis. </p><p>Hu et al. (2006) showed that S227P mutant fibulin-5 is synthesized and secreted at a reduced rate compared to wildtype. The mutant also failed to be incorporated into elastic fibers by transfected rat lung fibroblasts. Purified recombinant S227P fibulin-5 showed reduced affinity for tropoelastin in solid-phase binding assays as well as impaired association with fibrillin-1 microfibrils; in addition, the mutant protein triggered an endoplasmic reticulum (ER) stress response, as indicated by strong colocalization of the mutant with folding chaperones in the ER and by increased rates of apoptosis in patient fibroblasts. Histologic analysis of patient skin sections showed a lack of fibulin-5 in the extracellular matrix and concomitant disorganization of dermal elastic fibers, and electron microscopy of patient elastic fibers showed a failure of elastin globules to fuse into a continuous elastic fiber core. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CUTIS LAXA, AUTOSOMAL DOMINANT 2 (1 patient)</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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FBLN5, 483-BP DUP
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<br />
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ClinVar: RCV000005810
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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>Markova et al. (2003) analyzed the expression of the elastin gene and the fibulin genes 1 through 5 in fibroblasts from 5 patients with cutis laxa (ADCL2; 614434). One patient was found to express both normal (2.2 kb) and mutant (2.7 kb) fibulin-5 mRNA transcripts. The larger transcript contained an internal duplication of 483 nucleotides, which resulted in the synthesis and secretion of a mutant fibulin-5 protein with 4 additional tandem calcium-binding epidermal growth factor-like motifs. The mutation arose from a 22-kb tandem gene duplication, encompassing the sequence from intron 4 to exon 9. No fibulin-5 or elastin mutations were detected in the other 4 patients. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, VAL60LEU
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<br />
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SNP: rs121434299,
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gnomAD: rs121434299,
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ClinVar: RCV000005811, RCV001851678, RCV003447069, RCV004751203
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.178G-C transversion in the FBLN5 gene, resulting in a val60-to-leu (V60L) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, ARG71GLN
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<br />
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SNP: rs121434300,
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gnomAD: rs121434300,
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ClinVar: RCV000005812, RCV001851679, RCV003447070
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.212G-A transition in the FBLN5 gene, resulting in an arg71-to-gln (R71Q) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </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 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, PRO87SER
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<br />
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SNP: rs121434301,
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gnomAD: rs121434301,
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ClinVar: RCV000005813, RCV003447071
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.259C-T transition in the FBLN5 gene, resulting in a pro87-to-ser (P87S) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </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 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, ILE169THR
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<br />
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SNP: rs28939072,
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ClinVar: RCV000005814, RCV003447072
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.506T-C transition in the FBLN5 gene, resulting in an ile169-to-thr (I169T) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </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 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, ARG351TRP
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<br />
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SNP: rs28939073,
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gnomAD: rs28939073,
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ClinVar: RCV000005815, RCV001119789, RCV001577844, RCV002251883, RCV002490323, RCV003447073, RCV004700191
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.1051C-T transition in the FBLN5 gene, resulting in an arg351-to-trp (R351W) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </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 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, ALA363THR
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<br />
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SNP: rs121434302,
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gnomAD: rs121434302,
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ClinVar: RCV000005816, RCV001851680, RCV003447074
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.1087G-A transition in the FBLN5 gene, resulting in an ala363-to-thr (A363T) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </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>.0009 MACULAR DEGENERATION, AGE-RELATED, 3</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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FBLN5, GLY412GLU
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<br />
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SNP: rs121434303,
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ClinVar: RCV000005817, RCV002512815, RCV003447075
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.1235G-A transition in the FBLN5 gene, resulting in a gly412-to-glu (G412E) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic. </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>.0010 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IA</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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FBLN5, CYS217ARG
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<br />
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SNP: rs80338766,
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ClinVar: RCV000020642, RCV003447089
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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 3 affected sibs from a consanguineous Lebanese family with severe generalized cutis laxa (ARCL1A; 219100), Callewaert et al. (2013) identified homozygosity for a 649T-C transition in the FBLN5 gene, resulting in a cys217-to-arg (C217R) substitution at a highly conserved residue in the fourth calcium-binding EGF-like domain. The female proband died of pulmonary emphysema and bronchiolitis at 11 months of age; her 2 affected brothers had milder pulmonary emphysema. Other features in the 3 sibs included peripheral pulmonary artery stenosis, aortic valve stenosis and/or insufficiency, pyloric stenosis, and inguinal hernias. Callewaert et al. (2013) noted that the C217R had previously been identified by Claus et al. (2008) in another Lebanese family with cutis laxa. </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>.0011 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IA</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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FBLN5, GLU391TER
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<br />
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SNP: rs80338767,
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ClinVar: RCV000020639, RCV003447087
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 19-month-old girl from a consanguineous Algerian family with severe generalized cutis laxa with facial involvement (ARCL1A; 219100), Callewaert et al. (2013) identified homozygosity for a 1171G-T transversion in the FBLN5 gene, resulting in a glu391-to-ter (E391X) substitution in the FBLN-specific domain. The mutation was present in heterozygosity in the unaffected parents and an unaffected sister. The mother had had 2 spontaneous abortions and 2 older sisters and a brother with cutis laxa had died in infancy. The proband had a high and broad forehead, low and broad nasal bridge, beaked nose, large dysplastic ears, sagging cheeks, and everted lower lip. Other features included severe emphysema, normal cardiac status by echocardiography, photophobia, hypotonicity, and normal mental status. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0012 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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FBLN5, ARG373CYS
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<br />
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SNP: rs864309526,
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ClinVar: RCV000756132, RCV001843302, RCV003447124
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</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of a large Austrian kindred (families A and B) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011), identified a heterozygous c.1117C-T transition (c.1117C-T, NM_006329.3) in exon 10 of the FBLN5 gene, resulting in an arg373-to-cys (R373C) substitution at a highly conserved residue in the fibulin-type C terminus. The mutation, which was found by analysis of protein coding genes within a region identified through linkage analysis, segregated with the disorder in the family and was not found in 317 control individuals or in the 1000 Genomes Project database. Functional studies of the variant were not performed. Nerve and muscle biopsy of 1 patient (B5) showed no obvious changes in the immunohistochemical staining patterns of FBLN5 and elastin, but skin biopsy from another patient (B9) showed mild changes in the structure and arrangement of FBLN5 and elastin; neither of these patients had clinical skin abnormalities or ARMD. </p><p>Safka Brozkova et al. (2013) identified a heterozygous R373C mutation in affected members of a Czech family with CMT1H. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in the dbSNP (build 132) or Exome Variant Server databases. Functional studies of the variant were not performed. Haplotype analysis indicated that the mutation occurred independently from that in the family reported by Auer-Grumbach et al. (2011). None of the Czech patients had ARMD. </p><p>In 3 affected members spanning 3 generations of a Chinese family with CMT1H, Cheng et al. (2017) identified a heterozygous R373C mutation in the FBLN5 gene. The mutation, which was found by targeted next-generation sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, with evidence of variable expressivity and age-dependent penetrance. Functional studies of the variant were not performed. </p><p>Safka Brozkova et al. (2020) identified a heterozygous R373C mutation in the FBLN5 gene in affected members of 15 unrelated families from Austria, the Czech Republic, and France with CMT1H. The mutation, which was found by exome sequencing and segregated with the disorder in the families, was not present in the gnomAD database. Haplotype analysis indicated that some of the Czech families shared a similar haplotype, although others had independent mutational events. Functional studies of the variant were not performed. Three of the families had previously been reported. </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 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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FBLN5, GLY90SER
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<br />
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SNP: rs144288844,
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gnomAD: rs144288844,
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ClinVar: RCV000202614, RCV000521928, RCV001121879, RCV001249315, RCV001843303, RCV003447125, RCV004816351, RCV004816352
|
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 5 affected members of a family (family C) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011) identified a heterozygous c.268G-A transition (c.268G-A, NM_006329.3) in exon 4 of the FBLN5 gene, resulting in a gly90-to-ser (G90S) substitution. The variant was not found in the 1000 Genomes Project database, in 517 control individuals, or in previous studies of 1,204 patients with ARMD or 766 control individuals. Two patients, 1 severely affected and 1 clinically asymptomatic, also carried a heterozygous A339T variant in the YARS gene (603623), but this variant did not segregate with the peripheral neuropathy in this family. Three affected family members had hyperelastic skin and 1 had ARMD. Functional studies of the variant were not performed. Skin biopsies from 2 patients with hyperelastic skin showed a marked increase in FBLN5 immunoreactivity, which was present as short plump fibers. An unrelated individual with sporadic occurrence of the disorder was also found to carry the G90S mutation. </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>.0014 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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FBLN5, VAL126MET ({dbSNP rs61734479})
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<br />
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SNP: rs61734479,
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|
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|
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gnomAD: rs61734479,
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|
|
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|
|
ClinVar: RCV000202603, RCV000405354, RCV000584853, RCV001843304, RCV003917823
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 members of a family (family D) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011) identified a heterozygous c.376G-A transition (rs61734479) in the FBLN5 gene, resulting in a val126-to-met (V126M) substitution at a conserved residue. The variant was also found in 2 of 317 supposed controls, both of whom were found to have peripheral neuropathy, as well as in 2 of 300 patients with age-related macular degeneration, 1 of whom had evidence of a peripheral neuropathy (patient data from Table 1). Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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<div>
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|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBLN5, ARG331HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs774735234,
|
|
|
|
|
|
gnomAD: rs774735234,
|
|
|
|
|
|
ClinVar: RCV001843340, RCV002034713, RCV002290773
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 patients from 3 unrelated families of Czech and German origin (CZ7, CZ8, and GE1) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Safka Brozkova et al. (2020) identified a heterozygous c.992G-A transition (c.992G-A, NM_006329.3) in the FBLN5 gene, resulting in an arg331-to-his (R331H) substitution at a highly conserved residue in the C-terminal domain. The mutation was present once in the gnomAD database. Segregation with the disorder was demonstrated in family CZ7. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1H</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBLN5, ASP329VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1172268284,
|
|
|
|
|
|
gnomAD: rs1172268284,
|
|
|
|
|
|
ClinVar: RCV001843339
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French parent and offspring (family FR2) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Safka Brozkova et al. (2020) identified a heterozygous c.986A-T transversion (c.986A-T, NM_006329.3) in the FBLN5 gene, resulting in an asp329-to-val (D329V) substitution at a highly conserved residue in the C-terminal domain. The mutation, which was found by exome sequencing, was present once in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
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<p />
|
|
</div>
|
|
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<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C.
|
|
<strong>Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.</strong>
|
|
Brain 134: 1839-1852, 2011.
|
|
|
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|
|
[PubMed: 21576112]
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[Full Text: https://doi.org/10.1093/brain/awr076]
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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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Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others.
|
|
<strong>Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.</strong>
|
|
Hum. Mutat. 34: 111-121, 2013.
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|
[PubMed: 22829427]
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[Full Text: https://doi.org/10.1002/humu.22165]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Cheng, S., Lv, H., Zhang, W., Wang, Z., Shi, X., Liang, W., Yuan, Y.
|
|
<strong>Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation.</strong>
|
|
Clin. Neuropath. 36: 171-177, 2017.
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[PubMed: 28332470]
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[Full Text: https://doi.org/10.5414/NP301011]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Claus, S., Fischer, J., Megarbane, H., Megarbane, A., Jobard, F., Debret, R., Peyrol, S., Saker, S., Devillers, M., Sommer, P., Damour, O.
|
|
<strong>A p.C217R mutation in fibulin-5 from cutis laxa patients is associated with incomplete extracellular matrix formation in a skin equivalent model.</strong>
|
|
J. Invest. Derm. 128: 1442-1450, 2008.
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[PubMed: 18185537]
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[Full Text: https://doi.org/10.1038/sj.jid.5701211]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Hu, Q., Loeys, B. L., Coucke, P. J., De Paepe, A., Mecham, R. P., Choi, J., Davis, E. C., Urban, Z.
|
|
<strong>Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa.</strong>
|
|
Hum. Molec. Genet. 15: 3379-3386, 2006.
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[PubMed: 17035250]
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[Full Text: https://doi.org/10.1093/hmg/ddl414]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T.
|
|
<strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong>
|
|
J. Biol. Chem. 282: 11805-11816, 2007.
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[PubMed: 17324935]
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[Full Text: https://doi.org/10.1074/jbc.M611029200]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Kowal, R. C., Jolsin, J. M., Olson, E. N., Schultz, R. A.
|
|
<strong>Assignment of fibulin-5 (FBLN5) to human chromosome 14q31 by in situ hybridization and radiation hybrid mapping.</strong>
|
|
Cytogenet. Cell Genet. 87: 2-3, 1999.
|
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|
[PubMed: 10640802]
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[Full Text: https://doi.org/10.1159/000015382]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
Loeys, B., van Maldergem, L., Mortier, G., Coucke, P., Gerniers, S., Naeyaert, J.-M., de Paepe, A.
|
|
<strong>Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa.</strong>
|
|
Hum. Molec. Genet. 11: 2113-2118, 2002.
|
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|
|
[PubMed: 12189163]
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[Full Text: https://doi.org/10.1093/hmg/11.18.2113]
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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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Lotery, A. J., Baas, D., Ridley, C., Jones, R. P. O., Klaver, C. C. W., Stone, E., Nakamura, T., Luff, A., Griffiths, H., Wang, T., Bergen, A. A. B., Trump, D.
|
|
<strong>Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa.</strong>
|
|
Hum. Mutat. 27: 568-574, 2006.
|
|
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|
|
[PubMed: 16652333]
|
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|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20344]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Markova, D., Zou, Y., Ringpfeil, F., Sasaki, T., Kostka, G., Timpl, R., Uitto, J., Chu, M.-L.
|
|
<strong>Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene.</strong>
|
|
Am. J. Hum. Genet. 72: 998-1004, 2003.
|
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|
|
[PubMed: 12618961]
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[Full Text: https://doi.org/10.1086/373940]
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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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Mullins, R. F., Olvera, M. A., Clark, A. F., Stone, E. M.
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Nakamura, T., Lozano, P. R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C.-F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross, J., Jr., Honjo, T., Chien, K. R.
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<strong>Fibulin-5/DANCE is essential for elastogenesis in vivo.</strong>
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Nature 415: 171-175, 2002.
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Nakamura, T., Ruiz-Lozano, P., Lindner, V., Yabe, D., Taniwaki, M., Furukawa, Y., Kobuke, K., Tashiro, K., Lu, Z., Andon, N. L., Schaub, R., Matsumori, A., Sasayama, S., Chien, K. R., Honjo, T.
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<strong>DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.</strong>
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Safka Brozkova, D., Lassuthova, P., Neupauerova, J., Krutova, M., Haberlova, J., Stejskal, D., Seeman, P.
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<strong>Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth type 1 neuropathy. (Letter)</strong>
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Brain 136: e232, 2013. Note: Electronic Article.
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Safka Brozkova, D., Stojkovic, T., Haberlova, J., Mazanec, R., Windhager, R., Fernandes Rosenegger, P., Hacker, S., Zuchner, S., Kochanski, A., Leonard-Louis, S., Francou, B., Latour, P., Senderek, J., Seeman, P., Auer-Grumbach, M.
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Van Maldergem, L., Vamos, E., Liebaers, I., Petit, P., Vandevelde, G., Simonis-Blumenfrucht, A., Bouffioux, R., Kulakowski, S., Hanquinet, S., Van Durme, P., Laporte, M., Ledoux-Corbusier, M.
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Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N.
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<strong>Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.</strong>
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Cassandra L. Kniffin - updated : 02/24/2022<br>Cassandra L. Kniffin - updated : 12/10/2015<br>Patricia A. Hartz - updated : 11/4/2013<br>Patricia A. Hartz - updated : 11/4/2013<br>Marla J. F. O'Neill - updated : 2/14/2013<br>Marla J. F. O'Neill - updated : 2/13/2013<br>Jane Kelly - updated : 10/19/2007<br>Victor A. McKusick - updated : 7/12/2006<br>Marla J. F. O'Neill - updated : 8/11/2004<br>Victor A. McKusick - updated : 4/10/2003<br>George E. Tiller - updated : 12/10/2002<br>Ada Hamosh - updated : 1/11/2002<br>Carol A. Bocchini - updated : 2/15/2001
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