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Entry
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- *130160 - ELASTIN; ELN
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- OMIM
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<p>
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<span class="h4">*130160</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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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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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<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/130160">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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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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<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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<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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<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=ENSG00000049540;t=ENST00000252034" 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=2006" 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=130160" 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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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000049540;t=ENST00000252034" 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_000501,NM_001081752,NM_001081753,NM_001081754,NM_001081755,NM_001278912,NM_001278913,NM_001278914,NM_001278915,NM_001278916,NM_001278917,NM_001278918,NM_001278939,XM_005250187,XM_005250188,XM_011515868,XM_011515869,XM_011515870,XM_011515871,XM_011515872,XM_011515873,XM_011515874,XM_011515875,XM_011515876,XM_011515877,XM_017011813,XM_017011814,XM_047419954,XM_047419955,XM_047419956,XM_047419957,XM_047419958,XM_047419959,XM_047419960,XM_047419961,XM_047419962,XM_047419963,XM_047419964,XM_047419965,XM_047419966,XM_047419967,XM_047419968,XM_047419969,XM_047419970,XM_047419971,XM_047419972,XM_047419973,XM_047419974,XM_047419975,XM_047419976,XM_047419977,XM_047419978,XM_047419979,XM_047419980,XM_047419981" 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_000501" 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=130160" 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=00556&isoform_id=00556_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/ELN" 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/182019,182020,182021,182062,182064,553276,579846,1389764,1432162,1657754,2062393,2228743,2304982,4262773,22761674,22761779,31873977,31874660,34527924,34531631,41388841,41472283,46408209,62087464,119590030,119590031,119590032,119590033,119590034,119590035,119590036,119590037,119590038,119590039,119590040,119590041,119590042,126352322,126352440,126352446,126352608,126352700,152112966,193787294,193787618,193788294,194389196,525313599,525314478,525314483,525314487,525314491,525314495,525314499,525314504,530385573,530385575,767947000,767947002,767947004,767947006,767947008,767947010,767947012,767947014,767947016,767947018,1034654363,1034654365,1431906486,2217365854,2217365857,2217365859,2217365861,2217365863,2217365865,2217365867,2217365869,2217365873,2217365875,2217365877,2217365879,2217365881,2217365884,2217365886,2217365888,2217365890,2217365892,2217365894,2217365896,2217365898,2217365900,2217365902,2217365904,2217365906,2217365908,2217365910,2217365912,2462612706,2462612708,2462612710,2462612712,2462612714,2462612716,2462612718,2462612720,2462612722,2462612724,2462612726,2462612728,2462612731,2462612733,2462612735,2462612737,2462612739,2462612741,2462612743,2462612745,2462612747,2462612749,2462612751,2462612753,2462612755,2462612757,2462612759,2462612761,2462612763,2462612765,2462612767,2462612769,2462612771,2462612773,2462612775,2462612777,2462612779,2462612781,2462612783,2462612785,2462612787,2462612789" 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/P15502" 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=2006" 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=ENSG00000049540;t=ENST00000252034" 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=ELN" 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=ELN" 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+2006" 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/ELN" 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:2006" 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/2006" 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=chr7&hgg_gene=ENST00000252034.12&hgg_start=74028173&hgg_end=74069907&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">
|
|
<span class="panel-title">
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<span class="small">
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|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3327" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3327" 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/eln" 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=130160[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=130160[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/ELN/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000049540" 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=ELN" 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=ELN" 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=ELN" 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=ELN&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/PA27757" 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:3327" 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:95317" 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/ELN#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:95317" 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/2006/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=2006" 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-061212-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
|
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:130160" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2006" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=ELN&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 268185002<br />
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<strong>ICD10CM:</strong> Q25.3<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
130160
|
|
</span>
|
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</span>
|
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</div>
|
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</div>
|
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<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
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|
ELASTIN; ELN
|
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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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ELN" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ELN</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>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/7/331?start=-3&limit=10&highlight=331">7q11.23</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:74028173-74069907&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'})">7:74,028,173-74,069,907</a> </span>
|
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</em>
|
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</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>
|
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<div style="margin-bottom: 10px;">
|
|
<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">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=123700,185500" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
|
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</th>
|
|
<th>
|
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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<a href="/geneMap/7/331?start=-3&limit=10&highlight=331">
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7q11.23
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<span class="mim-font">
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Cutis laxa, autosomal dominant
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<span class="mim-font">
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<a href="/entry/123700"> 123700 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
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Supravalvar aortic stenosis
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<span class="mim-font">
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<a href="/entry/185500"> 185500 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/130160" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/130160" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Cloning and Expression</strong>
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<p>Elastic fibers are composed of 2 distinct components, a more abundant amorphous component (elastin) and the microfibrillar component. Elastin is composed largely of glycine, proline, and other hydrophobic residues and contains multiple lysine-derived crosslinks, such as desmosines, which link the individual polypeptide chains into a rubberlike network. The hydrophobic regions of the chains between the crosslinks are highly mobile. The hydrophobic and crosslinking domains are coded by separate, small (27 to 114 bp) exons that are separated by large introns. The initial translation product is a 72-kD polypeptide, designated tropoelastin (<a href="#29" class="mim-tip-reference" title="Rosenbloom, J. <strong>Elastin: relation of protein and gene structure to disease.</strong> Lab. Invest. 51: 605-623, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6150137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6150137</a>]" pmid="6150137">Rosenbloom, 1984</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6150137" 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="Indik, Z., Yeh, H., Ornstein-Goldstein, N., Sheppard, P., Anderson, N., Rosenbloom, J. C., Peltonen, L., Rosenbloom, J. <strong>Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA.</strong> Proc. Nat. Acad. Sci. 84: 5680-5684, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3039501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3039501</a>] [<a href="https://doi.org/10.1073/pnas.84.16.5680" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3039501">Indik et al. (1987)</a> cloned human elastin cDNA and found that it encodes a deduced 786-amino acid protein. They described alternative splicing of elastin mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3039501" 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="#35" class="mim-tip-reference" title="Uitto, J., Christiano, A. M., Kahari, V.-M., Bashir, M. M., Rosenbloom, J. <strong>Molecular biology and pathology of human elastin.</strong> Biochem. Soc. Trans. 19: 824-829, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1794566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1794566</a>] [<a href="https://doi.org/10.1042/bst0190824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1794566">Uitto et al. (1991)</a> reviewed the molecular biology of human elastin. Elastin is initially synthesized as a soluble polypeptide of approximately 72 kD. The individual elastin molecules are aligned on a scaffolding of microfibrils composed of fibrillin (<a href="/entry/134797">134797</a>). This alignment is stabilized by the formation of intermolecular crosslinks known as desmosines, which contribute to the insolubility of elastin. Formation of desmosines is initiated by oxidative deamination of certain lysyl residues by lysyl oxidase, a copper-dependent enzyme. The elastin polypeptides are encoded by an mRNA of approximately 3.5 kb which comprises a 2.2-kb coding segment and a relatively large 1.3-kb, 3-prime untranslated region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1794566" 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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<br />
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<div>
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<a id="mapping" class="mim-anchor"></a>
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<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Mapping</strong>
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<p><a href="#6" class="mim-tip-reference" title="Emanuel, B. S., Cannizzaro, L., Ornstein-Goldstein, N., Indik, Z. K., Yoon, K., May, M., Oliver, L., Boyd, C., Rosenbloom, J. <strong>Chromosomal localization of the human elastin gene.</strong> Am. J. Hum. Genet. 37: 873-882, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3840328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3840328</a>]" pmid="3840328">Emanuel et al. (1985)</a> provisionally assigned the elastin gene to 2q31-qter. <a href="#11" class="mim-tip-reference" title="Fazio, M. J., Mattei, M.-G., Passage, E., Chu, M.-L., Black, D., Solomon, E., Davidson, J. M., Uitto, J. <strong>Human elastin gene: new evidence for localization to the long arm of chromosome 7.</strong> Am. J. Hum. Genet. 48: 696-703, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2014796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2014796</a>]" pmid="2014796">Fazio et al. (1991)</a> used human elastin cDNAs in both in situ hybridization and Southern analysis of human-rodent cell hybrids to map the elastin gene to 7q11.2. PCR analysis with elastin-specific primers of DNA from a hybrid cell line containing only human chromosome 7 yielded a product of the expected size, while DNA containing human chromosome 2, but not chromosome 7, did not result in a product. <a href="#12" class="mim-tip-reference" title="Foster, K., Ferrell, R., King-Underwood, L., Povey, S., Attwood, J., Rennick, R., Humphries, S. E., Henney, A. M. <strong>Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7.</strong> Ann. Hum. Genet. 57: 87-96, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8368807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8368807</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1993.tb00890.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8368807">Foster et al. (1993)</a> described a dinucleotide repeat polymorphism in the ELN gene and used it to confirm assignment to chromosome 7 as well as to exclude the gene from chromosome 2 by linkage studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8368807+2014796+3840328" 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="#41" class="mim-tip-reference" title="Wydner, K. S., Sechler, J. L., Boyd, C. D., Passmore, H. C. <strong>Use of an intron length polymorphism to localize the tropoelastin gene to mouse chromosome 5 in a region of linkage conservation with human chromosome 7.</strong> Genomics 23: 125-131, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7829060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7829060</a>] [<a href="https://doi.org/10.1006/geno.1994.1467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7829060">Wydner et al. (1994)</a> used PCR primers complementary to regions of the mouse tropoelastin mRNA to define a novel intron length polymorphism (ILP) within intron 8 of the mouse elastin gene. Using this polymorphism in an interspecific backcross, they mapped the mouse Eln gene to the distal half of chromosome 5 in a region of homology of synteny of human chromosome 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829060" 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="geneStructure" class="mim-anchor"></a>
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<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Gene Structure</strong>
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<p><a href="#16" class="mim-tip-reference" title="Indik, Z., Yoon, K., Morrow, S. D., Cicila, G., Rosenbloom, J., Rosenbloom, J., Ornstein-Goldstein, N. <strong>Structure of the 3-prime region of the human elastin gene: great abundance of Alu repetitive sequences and few coding sequences.</strong> Connect. Tissue Res. 16: 197-211, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3038460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3038460</a>] [<a href="https://doi.org/10.3109/03008208709006976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3038460">Indik et al. (1987)</a> found a dearth of coding sequences and a remarkable abundance of Alu repetitive sequences in the 3-prime region of the human elastin gene. This suggested to them that, mediated by recombination between Alu sequences, considerable polymorphism may exist in the human population and between species. <a href="#34" class="mim-tip-reference" title="Tromp, G., Christiano, A., Goldstein, N., Indik, Z., Boyd, C., Rosenbloom, J., Deak, S., Prockop, D., Kuivaniemi, H. <strong>A to G polymorphism in ELN gene.</strong> Nucleic Acids Res. 19: 4314 only, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1871001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1871001</a>] [<a href="https://doi.org/10.1093/nar/19.15.4314-a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1871001">Tromp et al. (1991)</a> identified a RFLP in the ELN gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3038460+1871001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The human ELN gene has 34 exons and spans a total of approximately 45 kb of genomic DNA. The exon/intron ratio is unusually low, approximately 1:19 (<a href="#35" class="mim-tip-reference" title="Uitto, J., Christiano, A. M., Kahari, V.-M., Bashir, M. M., Rosenbloom, J. <strong>Molecular biology and pathology of human elastin.</strong> Biochem. Soc. Trans. 19: 824-829, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1794566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1794566</a>] [<a href="https://doi.org/10.1042/bst0190824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1794566">Uitto et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1794566" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#19" class="mim-tip-reference" title="Li, D. Y., Brooke, B., Davis, E. C., Mecham, R. P., Sorensen, L. K., Boak, B. B., Eichwald, E., Keating, M. T. <strong>Elastin is an essential determinant of arterial morphogenesis.</strong> Nature 393: 276-280, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9607766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9607766</a>] [<a href="https://doi.org/10.1038/30522" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9607766">Li et al. (1998)</a> defined the role of elastin in arterial development and disease by generating mice lacking elastin. These mice died of an obstructive arterial disease that resulted from subendothelial cell proliferation and reorganization of smooth muscle. These cellular changes were similar to those seen in atherosclerosis; however, lack of elastin was not associated with endothelial damage, thrombosis, or inflammation, which occur in models of atherosclerosis. Hemodynamic stress was not associated with arterial obstruction in these mice either, as the disease still occurred in arteries that were isolated in organ culture and therefore not subject to hemodynamic stress. Disruption of elastin was enough to induce subendothelial proliferation of smooth muscle and may contribute to obstructive arterial disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9607766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To investigate why a loss-of-function mutation in 1 elastin allele causes an inherited obstructive arterial disease, supravalvular aortic stenosis, <a href="#20" class="mim-tip-reference" title="Li, D. Y., Faury, G., Taylor, D. G., Davis, E. C., Boyle, W. A., Mecham, R. P., Stenzel, P., Boak, B., Keating, M. T. <strong>Novel arterial pathology in mice and humans hemizygous for elastin.</strong> J. Clin. Invest. 102: 1783-1787, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9819363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9819363</a>] [<a href="https://doi.org/10.1172/JCI4487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9819363">Li et al. (1998)</a> generated mice hemizygous for the elastin gene (Eln +/-). Although ELN mRNA and protein were reduced by 50% in Eln +/- mice, arterial compliance at physiologic pressures was nearly normal. This discrepancy was explained by a paradoxical increase of 35% in the number of elastic lamellae and smooth muscle in Eln +/- arteries. Examination of humans with ELN hemizygosity revealed a 2.5-fold increase in elastic lamellae and smooth muscle. Thus, ELN hemizygosity in mice and humans induces a compensatory increase in the number of rings of elastic lamellae and smooth muscle during arterial development. Humans are exquisitely sensitive to reduced ELN expression, developing profound arterial thickening and markedly increased risk of obstructive vascular disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9819363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Lee, S.-H., Goswami, S., Grudo, A., Song, L., Bandi, V., Goodnight-White, S., Green, L., Hacken-Bitar, J., Huh, J., Bakaeen, F., Coxson, H. O., Cogswell, S., Storness-Bliss, C., Corry, D. B., Kheradmand, F. <strong>Antielastin autoimmunity in tobacco smoking-induced emphysema.</strong> Nature Med. 13: 567-569, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17450149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17450149</a>] [<a href="https://doi.org/10.1038/nm1583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17450149">Lee et al. (2007)</a> studied the immune responses of age-matched smokers with and without emphysema (see COPD; <a href="/entry/606963">606963</a>) and found that differential responsiveness of T cells to elastin peptides, but not to collagen (see COL6A1; <a href="/entry/120220">120220</a>) or albumin (ALB; <a href="/entry/103600">103600</a>), correlated with emphysema severity. Compared with controls, COPD patients secreted increased levels of IFNG (<a href="/entry/147570">147570</a>) and IL10 (<a href="/entry/124092">124092</a>) in response to elastin peptides in an MHC II-dependent manner. Antibody to elastin, but not to collagen, was also increased in emphysema patients, as were lung B cells secreting antibody to the protein. Although regulatory T cell (Treg) responses did not differ between subject and control peripheral blood cells, emphysema patients showed a significant reduction of lung Tregs compared with controls. <a href="#18" class="mim-tip-reference" title="Lee, S.-H., Goswami, S., Grudo, A., Song, L., Bandi, V., Goodnight-White, S., Green, L., Hacken-Bitar, J., Huh, J., Bakaeen, F., Coxson, H. O., Cogswell, S., Storness-Bliss, C., Corry, D. B., Kheradmand, F. <strong>Antielastin autoimmunity in tobacco smoking-induced emphysema.</strong> Nature Med. 13: 567-569, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17450149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17450149</a>] [<a href="https://doi.org/10.1038/nm1583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17450149">Lee et al. (2007)</a> concluded that antielastin autoimmunity, possibly resulting from secretion of proteolytic enzymes induced by cigarette smoke exposure, is associated with an inflammatory response leading to emphysema and to tobacco-related pathology in other organs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17450149" 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>Role in Williams-Beuren Syndrome</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Curran, M. E., Atkinson, D. L., Ewart, A. K., Morris, C. A., Leppert, M. F., Keating, M. T. <strong>The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis.</strong> Cell 73: 159-168, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8096434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8096434</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90168-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8096434">Curran et al. (1993)</a> showed that the ELN gene was disrupted in a translocation with a breakpoint at 7q11.23. Exon 28 of the gene was the site of the breakpoint. Furthermore, <a href="#9" class="mim-tip-reference" title="Ewart, A. K., Morris, C. A., Ensing, G. J., Loker, J., Moore, C., Leppert, M., Keating, M. <strong>A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.</strong> Proc. Nat. Acad. Sci. 90: 3226-3230, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8475063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8475063</a>] [<a href="https://doi.org/10.1073/pnas.90.8.3226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8475063">Ewart et al. (1993)</a> showed close linkage of ELN and supravalvular aortic stenosis (SVAS; <a href="/entry/185500">185500</a>) in 2 families. <a href="#8" class="mim-tip-reference" title="Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A. D., Leppert, M., Keating, M. T. <strong>Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.</strong> Nature Genet. 5: 11-16, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7693128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7693128</a>] [<a href="https://doi.org/10.1038/ng0993-11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7693128">Ewart et al. (1993)</a> found that deletion involving 7q11.23 and resulting in hemizygosity of the elastin gene is responsible for the Williams-Beuren syndrome (WBS; <a href="/entry/194050">194050</a>). Deletions limited to the elastin gene appear to result in SVAS, whereas deletions spanning at least 114 kb lead to the Williams syndrome. Thus, the latter is a contiguous gene syndrome with neurobehavioral features and mental retardation not easily accounted for by the disruption of the elastin gene alone. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8475063+8096434+7693128" 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="#27" class="mim-tip-reference" title="Perez Jurado, L. A., Peoples, R., Kaplan, P., Hamel, B. C. J., Francke, U. <strong>Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth.</strong> Am. J. Hum. Genet. 59: 781-792, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8808592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8808592</a>]" pmid="8808592">Perez Jurado et al. (1996)</a> reported that 61 of 65 clinically defined patients with Williams-Beuren syndrome had a deletion of the ELN locus. They noted that no variability in the size of the deletion could be detected between WBS patients by genotyping of polymorphic markers, suggesting that the chromosomal breakpoints in these patients fell into narrowly defined physical regions. <a href="#27" class="mim-tip-reference" title="Perez Jurado, L. A., Peoples, R., Kaplan, P., Hamel, B. C. J., Francke, U. <strong>Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth.</strong> Am. J. Hum. Genet. 59: 781-792, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8808592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8808592</a>]" pmid="8808592">Perez Jurado et al. (1996)</a> also compared clinical differences between maternally and paternally inherited ELN deletions and postulated that an imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8808592" 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="Duba, H.-C., Doll, A., Neyer, M., Erdel, M., Mann, C., Hammerer, I., Utermann, G., Grzeschik, K.-H. <strong>The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome.</strong> Europ. J. Hum. Genet. 10: 351-361, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080386</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200812" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080386">Duba et al. (2002)</a> investigated a family with a cytogenetically balanced translocation t(7;16)(q11.23;q13) in which the 5 translocation carriers manifested a wide variation in phenotype, ranging from a hoarse voice as the only feature, partial WBS with or without SVAS, to the full WBS phenotype. DNA sequence analysis showed that the breakpoint on chromosome 7 was within intron 5 of the ELN gene and on chromosome 16 within intron 1 of the GPR56 gene (<a href="/entry/604110">604110</a>). In the course of the rearrangement, no basepair was lost from either the chromosome 7 or chromosome 16 sequences. <a href="#5" class="mim-tip-reference" title="Duba, H.-C., Doll, A., Neyer, M., Erdel, M., Mann, C., Hammerer, I., Utermann, G., Grzeschik, K.-H. <strong>The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome.</strong> Europ. J. Hum. Genet. 10: 351-361, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080386</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200812" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080386">Duba et al. (2002)</a> speculated that the expected phenotype in the reported family would be SVAS, not WBS, and proposed a long-range position effect caused by the translocation event as the most likely explanation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12080386" 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>Supravalvular Aortic Stenosis</em></strong></p><p>
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In a family with SVAS (<a href="/entry/185500">185500</a>), <a href="#7" class="mim-tip-reference" title="Ewart, A. K., Jin, W., Atkinson, D., Morris, C. A., Keating, M. T. <strong>Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.</strong> J. Clin. Invest. 93: 1071-1077, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8132745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8132745</a>] [<a href="https://doi.org/10.1172/JCI117057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8132745">Ewart et al. (1994)</a> found, by pulsed field, PCR, and Southern analysis, a 100-kb deletion of the 3-prime end of the elastin gene cosegregating with the disease (<a href="#0001">130160.0001</a>). DNA sequence analysis localized the breakpoint of the deletion between elastin exons 27 and 28, the same region disrupted by the SVAS-associated translocation. The family included an affected mother and daughter. The daughter had right ventricular hypertrophy, supravalvular pulmonic stenosis, bilateral narrowing of the pulmonary arteries (left more severe than right), and a diffusely narrowed ascending aorta with a discrete supravalvular narrowing diagnosed by cardiac catheterization at 6 weeks of age. The patient also had intermittent acrocyanosis and hypertension. At 16 months of age, the supravalvular pulmonic stenosis had improved. The proband also had some features common to Williams syndrome, including dolichocephaly, bitemporal narrowness, outer canthal distance less than 2 SD below the mean, periorbital fullness, broad mouth, full cheeks, hoarse voice, and hypersensitivity to loud noises. The diagnosis of Williams syndrome was not made because she had normal serum calcium levels, a normal urine calcium/creatinine ratio, normal psychomotor development, and normal growth parameters. The child was treated with phenobarbital for seizures. The mother had had seizures in adolescence. Since childhood, she had had a grade III (out of VI) early systolic murmur heard best at the suprasternal notch and radiating to the left carotid. At least 2 other family members were affected by SVAS. The mother's brother had narrowing of the entire pulmonary arterial tree documented by cardiac catheterization and was treated for seizures. A maternal first cousin had severe bilateral peripheral pulmonic stenosis, right ventricular hypertrophy, and mild SVAS demonstrated by echocardiogram. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8132745" 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>Gross rearrangements of the ELN gene have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for SVAS, <a href="#21" class="mim-tip-reference" title="Li, D. Y., Toland, A. E., Boak, B. B., Atkinson, D. L., Ensing, G. J., Morris, C. A., Keating, M. T. <strong>Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1021-1028, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215670</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215670">Li et al. (1997)</a> refined the genomic structure of the gene and used this information in mutation analyses. ELN point mutations were found to cosegregate with the disease in 4 familial cases (e.g., <a href="#0005">130160.0005</a>) and to be associated with SVAS in 3 sporadic cases (<a href="#0004">130160.0004</a>). Two of the mutations were nonsense, 1 was a single bp deletion, and 4 were splice site mutations. In 1 sporadic case, the mutation had arisen de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215670" 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="#32" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Donnai, D., Hurst, J., Reardon, W., Burch, M., Read, A. P. <strong>Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1029-1036, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215671</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215671">Tassabehji et al. (1997)</a> described the complete exon-intron structure of the ELN gene. All exons are in-frame, allowing exon skipping without disrupting the reading frame. Microsatellites were located in introns 17 and 18. They found that isolated SVAS was associated with point mutations that predicted premature chain termination. They stated that in their experience all patients with a classic Williams syndrome phenotype had been found to be hemizygous at the elastin locus; nevertheless, only 5% had severe clinical SVAS. In their 2 SVAS families with point mutations, each mutation manifested as severe SVAS in the proband, but as mild cardiac features or nonpenetrance in the mothers. <a href="#32" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Donnai, D., Hurst, J., Reardon, W., Burch, M., Read, A. P. <strong>Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1029-1036, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215671</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215671">Tassabehji et al. (1997)</a> considered such variability typical of phenotypes produced by haploinsufficiency, where genetic background is expected to have a major modifying effect. An alternative hypothesis is that a dominant-negative elastin mutation results if truncated proteins have some, but not all, domains critical for intermolecular interactions and thus may disrupt posttranslational processing and development of elastic fibers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Koch, A., Buheitel, G., Hofbeck, M., Rauch, A., Kraus, C., Tassabehji, M., Singer, H. <strong>Spectrum of arterial obstructions caused by one elastin gene point mutation.</strong> Europ. J. Pediat. 162: 53-54, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12607532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12607532</a>] [<a href="https://doi.org/10.1007/s00431-002-1111-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12607532">Koch et al. (2003)</a> similarly found the complete spectrum of arterial stenoses in 5 members of an extended pedigree with a confirmed nonsense mutation haplotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12607532" 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="#37" class="mim-tip-reference" title="Urban, Z., Michels, V. V., Thibodeau, S. N., Davis, E. C., Bonnefont, J.-P., Munnich, A., Eyskens, B., Gewillig, M., Devriendt, K., Boyd, C. D. <strong>Isolated supravalvular aortic stenosis: functional haploinsufficiency of the elastin gene as a result of nonsense-mediated decay.</strong> Hum. Genet. 106: 577-588, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942104</a>] [<a href="https://doi.org/10.1007/s004390000285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10942104">Urban et al. (2000)</a> used single-strand conformation and heteroduplex analyses of genomic amplimers to identify point mutations within the ELN gene in patients with nonsyndromic SVAS from a total of 8 unrelated families. They identified 6 novel point mutations. Nonpenetrance was demonstrated in some of the families. Together with the new mutations they found, 14 point mutations had been reported in SVAS patients, and 10 of these resulted in premature stop codons (PTCs). They analyzed the expression of ELN alleles in skin fibroblasts from 1 SVAS patient and showed that PTC mutations resulted in selective elimination of mutant transcripts. Inhibition of the nonsense-mediated decay mechanism by cycloheximide resulted in the stabilization of mutant elastin mRNA. Allelic inactivation by the ELN mutation in this patient led to an overall decrease of the steady-state levels of elastin mRNA. In the skin fibroblasts from the same SVAS patient, they demonstrated reduced synthesis and secretion of tropoelastin. Given the predominance of PTC mutations in SVAS, <a href="#37" class="mim-tip-reference" title="Urban, Z., Michels, V. V., Thibodeau, S. N., Davis, E. C., Bonnefont, J.-P., Munnich, A., Eyskens, B., Gewillig, M., Devriendt, K., Boyd, C. D. <strong>Isolated supravalvular aortic stenosis: functional haploinsufficiency of the elastin gene as a result of nonsense-mediated decay.</strong> Hum. Genet. 106: 577-588, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942104</a>] [<a href="https://doi.org/10.1007/s004390000285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10942104">Urban et al. (2000)</a> suggested that functional haploinsufficiency may be the pathomechanism underlying most cases of nonsyndromic SVAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Metcalfe, K., Rucka, A. K., Smoot, L., Hofstadler, G., Tuzler, G., McKeown, P., Siu, V., Rauch, A., Dean, J., Dennis, N., Ellis, I., Reardon, W., Cytrynbaum, C., Osborne, L., Yates, J. R., Read, A. P., Donnai, D., Tassabehji, M. <strong>Elastin: mutational spectrum in supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 8: 955-963, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175284</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175284">Metcalfe et al. (2000)</a> used SSCP and heteroduplex analysis to screen 100 unrelated patients with SVAS and normal karyotypes without major deletions of the ELN gene as determined by FISH. All 34 exons of the ELN gene were screened and mutations were identified in 35 of the patients. The mutations were 23 nonsense or frameshift mutations predicted to cause premature termination, 6 splice site mutations, 4 missense mutations, and 2 small deletions in exon 1 encompassing the ATG initiation codon. The 35 patients represented 24 familial cases, 10 sporadic cases, and 1 of unknown status. Recurrent mutations were the nonsense mutations Y150X in exon 9 (<a href="#0013">130160.0013</a>), Q442X in exon 21 (<a href="#0003">130160.0003</a>), and K176X in exon 10 (<a href="#0014">130160.0014</a>), which appeared to be mutation hotspots. A marked phenotypic intrafamilial variability was illustrated by 2 large families with multiple affected members with disease severity ranging from asymptomatic carriers to mild or severe SVAS requiring surgery, or sudden infant death. No obvious genotype-phenotype correlation was detected; cases with missense or splicing mutations were as likely to have severe SVAS as cases with truncating mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175284" 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="#39" class="mim-tip-reference" title="Urban, Z., Riazi, S., Seidl, T. L., Katahira, J., Smoot, L. B., Chitayat, D., Boyd, C. D., Hinek, A. <strong>Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome.</strong> Am. J. Hum. Genet. 71: 30-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12016585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12016585</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12016585[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/10.1086/341035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12016585">Urban et al. (2002)</a> compared both elastogenesis and proliferation rate of cultured aortic smooth-muscle cells (SMCs) and skin fibroblasts from 5 healthy control subjects, 4 patients with isolated SVAS, and 5 patients with WBS. Three mutations found in patients with SVAS were found to result in null alleles. RNA blood hybridization, immunostaining, and metabolic labeling experiments demonstrated that SVAS cells and WBS cells have reduced elastin mRNA levels and that they consequently deposit low amounts of insoluble elastin. Abnormally low levels of elastin deposition in SVAS cells and in WBS cells were found to coincide with an increase in proliferation rate, which could be reversed by addition of exogenous insoluble elastin. This led to the conclusion that insoluble elastin is an important regulator of cellular proliferation. The reduced net deposition of insoluble elastin in arterial walls of patients with either SVAS or WBS leads to the increased proliferation of arterial SMCs, which results in the formation of multilayer thickening of the tunica media of large arteries and, consequently, in the development of hyperplastic intimal lesions leading to segmental arterial occlusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12016585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Micale, L., Turturo, M. G., Fusco, C., Augello, B., Jurado, L. A. P., Izzi, C., Digilio, M. C., Milani, D., Lapi, E., Zelante, L., Merla, G. <strong>Identification and characterization of seven novel mutations of elastin gene in a cohort of patients affected by supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 18: 317-323, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19844261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19844261</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19844261[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/10.1038/ejhg.2009.181" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19844261">Micale et al. (2010)</a> analyzed the ELN gene in 31 familial and sporadic cases of SVAS and identified 7 novel mutations, including 5 frameshift mutations and 2 splice site mutations (see, e.g., <a href="#0020">130160.0020</a>). In vitro analysis of 3 of the frameshift mutations using minigene constructs and transfection assays confirmed that functional haploinsufficiency of the ELN gene is the main pathomechanism underlying SVAS. In addition, molecular analysis of patient fibroblasts showed that the 2044+5G-C (<a href="#0020">130160.0020</a>) mutant allele encodes an aberrant shorter form of the elastin polypeptide that may hamper the normal assembly of elastin fibers in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19844261" 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>Cutis Laxa</em></strong></p><p>
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In the cell line from a patient with cutis laxa (<a href="/entry/123700">123700</a>), <a href="#42" class="mim-tip-reference" title="Zhang, M. C., He, L., Yong, S. L., Tiller, G. E., Davidson, J. M. <strong>Cutis laxa arising from a frame shift mutation in the elastin gene (ELN). (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A353 only, 1997."None>Zhang et al. (1997)</a> identified heterozygosity for a 1-bp deletion in exon 30 of the ELN gene (<a href="#0008">130160.0008</a>). In a 30-year-old woman and her 2-year-old son, both of whom had classic cutis laxa, <a href="#44" class="mim-tip-reference" title="Zhang, M.-C., He, L., Giro, M., Yong, S. L., Tiller, G. E., Davidson, J. M. <strong>Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN).</strong> J. Biol. Chem. 274: 981-986, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9873040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9873040</a>] [<a href="https://doi.org/10.1074/jbc.274.2.981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9873040">Zhang et al. (1999)</a> identified heterozygosity for a different 1-bp deletion in the ELN gene (<a href="#0010">130160.0010</a>), also in exon 30. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9873040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 37-year-old Caucasian woman with cutis laxa, <a href="#33" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Hurst, J., Ashcroft, G. S., Kielty, C., Wilmot, C., Donnai, D., Read, A. P., Jones, C. J. P. <strong>An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa.</strong> Hum. Molec. Genet. 7: 1021-1028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9580666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9580666</a>] [<a href="https://doi.org/10.1093/hmg/7.6.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9580666">Tassabehji et al. (1998)</a> identified heterozygosity for a 1-bp deletion in the ELN gene (<a href="#0009">130160.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9580666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a mother and daughter with cutis laxa and severe pulmonary disease, originally described by <a href="#1" class="mim-tip-reference" title="Beighton, P. H. <strong>The dominant and recessive forms of cutis laxa.</strong> J. Med. Genet. 9: 216-221, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5046633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5046633</a>] [<a href="https://doi.org/10.1136/jmg.9.2.216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5046633">Beighton (1972)</a> and <a href="#3" class="mim-tip-reference" title="Corbett, E., Glaisyer, H., Chan, C., Madden, B., Khaghani, A., Yacoub, M. <strong>Congenital cutis laxa with a dominant inheritance and early onset emphysema.</strong> Thorax 49: 836-837, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8091333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8091333</a>] [<a href="https://doi.org/10.1136/thx.49.8.836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8091333">Corbett et al. (1994)</a>, <a href="#36" class="mim-tip-reference" title="Urban, Z., Gao, J., Pope, F. M., Davis, E. C. <strong>Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin.</strong> J. Invest. Derm. 124: 1193-1199, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15955094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15955094</a>] [<a href="https://doi.org/10.1111/j.0022-202X.2005.23758.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15955094">Urban et al. (2005)</a> identified no mutations in the elastin gene by direct sequencing, but detected an abnormal protein in cultured dermal fibroblasts using metabolic labeling and immunoprecipitation. Mutation and gene expression analyses established the presence of a complex tandem duplication in the elastin gene (<a href="#0016">130160.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5046633+15955094+8091333" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a 3-generation family of Japanese and German ancestry and an unrelated Singaporean girl of Chinese descent with cutis laxa and aortic aneurysmal disease, <a href="#31" class="mim-tip-reference" title="Szabo, Z., Crepeau, M. W., Mitchell, A. L., Stephan, M. J., Puntel, R. A., Loke, K. Y., Kirk, R. C., Urban, Z. <strong>Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. (Letter)</strong> J. Med. Genet. 43: 255-258, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16085695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16085695</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16085695[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.034157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16085695">Szabo et al. (2006)</a> identified heterozygosity for a 25-bp deletion (<a href="#0017">130160.0017</a>) and a 1-bp deletion (<a href="#0018">130160.0018</a>) in exon 30 of the ELN gene, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16085695" 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>Role in Other Disorders</em></strong></p><p>
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For a discussion of a possible association between variation in the ELN gene and susceptibility to intracranial berry aneurysm, see ANIB1 (<a href="/entry/105800">105800</a>).</p>
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<p><a href="#10" class="mim-tip-reference" title="Faury, G., Pezet, M., Knutsen, R. H., Boyle, W. A., Heximer, S. P., McLean, S. E., Minkes, R. K., Blumer, K. J., Kovacs, A., Kelly, D. P., Li, D. Y., Starcher, B., Mecham, R. P. <strong>Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency.</strong> J. Clin. Invest. 112: 1419-1428, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14597767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14597767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14597767[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI19028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14597767">Faury et al. (2003)</a> reported that Eln +/- mice were stably hypertensive from birth, with a mean arterial pressure 25 to 30 mm Hg higher than their wildtype counterparts. The animals had only moderate cardiac hypertrophy and lived a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln +/- arteries were generally smaller than wildtype arteries at any given intravascular pressure. Because the Eln +/- mice were hypertensive, however, the effective arterial working diameter was comparable to that of the normotensive wildtype animal. Physiologic studies indicated a role for the renin (<a href="/entry/179820">179820</a>)-angiotensin (see <a href="/entry/106150">106150</a>) system in maintaining the hypertensive state. <a href="#10" class="mim-tip-reference" title="Faury, G., Pezet, M., Knutsen, R. H., Boyle, W. A., Heximer, S. P., McLean, S. E., Minkes, R. K., Blumer, K. J., Kovacs, A., Kelly, D. P., Li, D. Y., Starcher, B., Mecham, R. P. <strong>Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency.</strong> J. Clin. Invest. 112: 1419-1428, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14597767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14597767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14597767[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI19028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14597767">Faury et al. (2003)</a> concluded that the association of hypertension with elastin haploinsufficiency in humans and mice strongly suggested that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14597767" 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="Hirano, E., Knutsen, R. H., Sugitani, H., Ciliberto, C. H., Mecham, R. P. <strong>Functional rescue of elastin insufficiency in mice by the human elastin gene.</strong> Circ. Res. 101: 523-531, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17626896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17626896</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.107.153510" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17626896">Hirano et al. (2007)</a> stated that the Eln gene in most mammalian species contains 36 exons. The rat and mouse Eln genes have 37 exons, whereas the human ELN gene has only 34 exons due to the sequential loss of 2 exons during primate evolution. In addition, although still contained within the human gene, exon 22 is rarely included in the elastin transcript. The mouse and human ELN proteins share only 64.1% amino acid identity. Because of the structural differences between mouse and human ELN, <a href="#14" class="mim-tip-reference" title="Hirano, E., Knutsen, R. H., Sugitani, H., Ciliberto, C. H., Mecham, R. P. <strong>Functional rescue of elastin insufficiency in mice by the human elastin gene.</strong> Circ. Res. 101: 523-531, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17626896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17626896</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.107.153510" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17626896">Hirano et al. (2007)</a> developed a humanized elastin mouse in which elastin production was controlled by a human ELN transgene. Expression of the human transgene reversed the hypertension and cardiovascular changes associated with Eln haploinsufficiency and rescued the perinatal lethality of the Eln-null phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17626896" 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 family with SVAS (<a href="/entry/185500">185500</a>), <a href="#7" class="mim-tip-reference" title="Ewart, A. K., Jin, W., Atkinson, D., Morris, C. A., Keating, M. T. <strong>Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.</strong> J. Clin. Invest. 93: 1071-1077, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8132745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8132745</a>] [<a href="https://doi.org/10.1172/JCI117057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8132745">Ewart et al. (1994)</a> found a heterozygous 100-kb deletion in the 3-prime end of the elastin gene with a breakpoint between elastin exons 27 and 28. The same region was disrupted in the familial reciprocal translocation reported by <a href="#24" class="mim-tip-reference" title="Morris, C. A., Loker, J., Ensing, G., Stock, A. D. <strong>Supravalvular aortic stenosis cosegregates with a familial 6;7 translocation which disrupts the elastin gene.</strong> Am. J. Med. Genet. 46: 737-744, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8362925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8362925</a>] [<a href="https://doi.org/10.1002/ajmg.1320460634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8362925">Morris et al. (1993)</a>. <a href="#7" class="mim-tip-reference" title="Ewart, A. K., Jin, W., Atkinson, D., Morris, C. A., Keating, M. T. <strong>Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.</strong> J. Clin. Invest. 93: 1071-1077, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8132745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8132745</a>] [<a href="https://doi.org/10.1172/JCI117057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8132745">Ewart et al. (1994)</a> pointed out that the protein product of the mutant gene would lack a microfibril-associated glycoprotein (MAGP; <a href="/entry/156790">156790</a>) binding site that normally exists in the C terminus of elastin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8132745+8362925" 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=RCV000018204" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018204" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018204</a>
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<p><a href="#26" class="mim-tip-reference" title="Olson, T. M., Michels, V. V., Urban, Z., Csiszar, K., Christiano, A. M., Driscoll, D. J., Feldt, R. H., Boyd, C. D., Thibodeau, S. N. <strong>A 30 kb deletion within the elastin gene results in familial supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 4: 1677-1679, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541862</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541862">Olson et al. (1995)</a> used Southern blot analysis to screen for mutations in the ELN gene in 6 familial and 3 sporadic cases of SVAS (<a href="/entry/185500">185500</a>) without features of Williams-Beuren syndrome (<a href="/entry/194050">194050</a>). The familial cases included members of a previously reported large pedigree with linkage to the elastin gene region (<a href="#25" class="mim-tip-reference" title="Olson, T. M., Michels, V. V., Lindor, N. M., Pastores, G. M., Weber, J. L., Schaid, D. J., Driscoll, D. J., Feldt, R. H., Thibodeau, S. N. <strong>Autosomal dominant supravalvular aortic stenosis: localization to chromosome 7.</strong> Hum. Molec. Genet. 2: 869-873, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364568</a>] [<a href="https://doi.org/10.1093/hmg/2.7.869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8364568">Olson et al., 1993</a>). A 30-kb deletion extending from breakpoints in intron 1 and intron 27 was found in 2 members of a Middle Eastern family. The proband developed severe SVAS and peripheral pulmonary artery stenosis and underwent aortic operation in early childhood. He had no evidence of Williams syndrome or clinically apparent abnormalities of other elastin-containing tissue. The deletion was also demonstrated in his mother, an obligate carrier with subtle disease (a heart murmur and a nondiagnostic echocardiogram). Blood for DNA analysis was not available from a maternal uncle with SVAS and a sister with isolated peripheral pulmonary artery stenosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8364568+8541862" 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">rs137854452 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137854452;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=rs137854452" 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=rs137854452" 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=RCV000018206 OR RCV000255419" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018206, RCV000255419" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018206...</a>
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<p><a href="#21" class="mim-tip-reference" title="Li, D. Y., Toland, A. E., Boak, B. B., Atkinson, D. L., Ensing, G. J., Morris, C. A., Keating, M. T. <strong>Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1021-1028, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215670</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215670">Li et al. (1997)</a> found a heterozygous nonsense mutation in a sporadic case of SVAS (<a href="/entry/185500">185500</a>): a C-to-T transition at nucleotide 1324, resulting in conversion of a glutamine to a premature stop codon (Q442X) in exon 21. DNA samples could not be obtained from the parents of the proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215670" 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="#32" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Donnai, D., Hurst, J., Reardon, W., Burch, M., Read, A. P. <strong>Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1029-1036, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215671</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215671">Tassabehji et al. (1997)</a> found the same mutation in a patient with SVAS. The patient had presented at the age of 8 weeks with a heart murmur and episodes of cyanosis. Echocardiography at 4 months of age showed SVAS and pulmonary arterial stenosis. These changes were progressive. Corrective open heart surgery was performed at the age of 21 months, at which time it was noted that the aorta and pulmonary arteries were very thick and abnormal. His mother had had cardiac follow-up for a heart murmur until the age of 6 years, but echocardiogram showed no evidence of SVAS and no pulmonary artery stenosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Metcalfe, K., Rucka, A. K., Smoot, L., Hofstadler, G., Tuzler, G., McKeown, P., Siu, V., Rauch, A., Dean, J., Dennis, N., Ellis, I., Reardon, W., Cytrynbaum, C., Osborne, L., Yates, J. R., Read, A. P., Donnai, D., Tassabehji, M. <strong>Elastin: mutational spectrum in supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 8: 955-963, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175284</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175284">Metcalfe et al. (2000)</a> found the Q442X mutation in 3 unrelated patients with SVAS among 100 patients screened. Haplotype analysis using ELN flanking and intragenic markers showed no evidence of a founder effect; therefore this appeared to be a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175284" 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> rs137854453 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137854453;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/rs137854453?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=rs137854453" 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=rs137854453" 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=RCV000018207 OR RCV000018221 OR RCV000198624 OR RCV004532381" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018207, RCV000018221, RCV000198624, RCV004532381" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018207...</a>
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<p>In a sporadic case of SVAS (<a href="/entry/185500">185500</a>), <a href="#21" class="mim-tip-reference" title="Li, D. Y., Toland, A. E., Boak, B. B., Atkinson, D. L., Ensing, G. J., Morris, C. A., Keating, M. T. <strong>Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1021-1028, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215670</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215670">Li et al. (1997)</a> found a nonsense mutation: a C-to-T transition at nucleotide 1708, resulting in conversion of arginine-570 to a premature stop codon in exon 25 (R570X). DNA samples could not be obtained from the parents of the proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Metcalfe, K., Rucka, A. K., Smoot, L., Hofstadler, G., Tuzler, G., McKeown, P., Siu, V., Rauch, A., Dean, J., Dennis, N., Ellis, I., Reardon, W., Cytrynbaum, C., Osborne, L., Yates, J. R., Read, A. P., Donnai, D., Tassabehji, M. <strong>Elastin: mutational spectrum in supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 8: 955-963, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175284</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175284">Metcalfe et al. (2000)</a> detected the R570X mutation in a sporadic case of SVAS with peripheral pulmonary artery stenosis and bilateral inguinal hernias. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175284" 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 primers amplifying exon 26 of the ELN gene, <a href="#21" class="mim-tip-reference" title="Li, D. Y., Toland, A. E., Boak, B. B., Atkinson, D. L., Ensing, G. J., Morris, C. A., Keating, M. T. <strong>Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1021-1028, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215670</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215670">Li et al. (1997)</a> identified an anomalous band that cosegregated with SVAS (<a href="/entry/185500">185500</a>) in 1 family. The aberrant conformer showed a single-nucleotide deletion at position 1821 in exon 26 (1821delC). This deletion caused a frameshift resulting in a premature stop codon in exon 28. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215670" 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">rs727503027 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727503027;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=rs727503027" 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=rs727503027" 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=RCV000150636" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000150636" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000150636</a>
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<p>In 2 unrelated kindreds, <a href="#21" class="mim-tip-reference" title="Li, D. Y., Toland, A. E., Boak, B. B., Atkinson, D. L., Ensing, G. J., Morris, C. A., Keating, M. T. <strong>Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1021-1028, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215670</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215670">Li et al. (1997)</a> found that SVAS (<a href="/entry/185500">185500</a>) segregated with an A-to-G transition at position -2 in the splice acceptor site of intron 15 preceding exon 16. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215670" 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">rs2132322943 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2132322943;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=rs2132322943" 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=rs2132322943" 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=RCV000018209" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018209" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018209</a>
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<p>In a patient with SVAS (<a href="/entry/185500">185500</a>), <a href="#32" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Donnai, D., Hurst, J., Reardon, W., Burch, M., Read, A. P. <strong>Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1029-1036, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215671</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215671">Tassabehji et al. (1997)</a> identified insertion of a T in codon 606 of exon 26 of the ELN gene, producing a frameshift predicted to cause premature termination 10 codons downstream. The patient presented at birth with a heart murmur. At the age of 3 years, echocardiography suggested SVAS on the basis of 'waisting' of the ascending aorta and poststenotic dilatation. A brother had died suddenly in the first year of life and at autopsy was noted to have spontaneously repaired SVAS, repaired central pulmonary artery stenosis, and marked ventricular hypertrophy. The aortic valve and proximal aorta were markedly dysplastic with extreme thickening beyond the valve. The proband's mother had presented to cardiologists in childhood with a murmur and a clinical diagnosis of aortic stenosis had been made. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215671" 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>.0008 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1797225811 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1797225811;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=rs1797225811" 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=rs1797225811" 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=RCV000018210" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018210" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018210</a>
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<p>In a patient with cutis laxa (<a href="/entry/123700">123700</a>), <a href="#43" class="mim-tip-reference" title="Zhang, M.-C., Giro, M., Quaglino, D., Jr., Davidson, J. M. <strong>Transforming growth factor-beta reverses a posttranscriptional defect in elastin synthesis in a cutis laxa skin fibroblast strain.</strong> J. Clin. Invest. 95: 986-994, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7884000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7884000</a>] [<a href="https://doi.org/10.1172/JCI117808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7884000">Zhang et al. (1995)</a> demonstrated decreased elastin mRNA levels in skin fibroblasts due to transcript instability. <a href="#42" class="mim-tip-reference" title="Zhang, M. C., He, L., Yong, S. L., Tiller, G. E., Davidson, J. M. <strong>Cutis laxa arising from a frame shift mutation in the elastin gene (ELN). (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A353 only, 1997."None>Zhang et al. (1997)</a> cloned and sequenced both ELN cDNA alleles in the cell line from this patient and identified a frameshift mutation, deletion of 2012G, in the C-terminal coding region of 1 allele. The patient was heterozygous for the single base deletion, which was not found in genomic DNA from either parent or from 65 unrelated control samples. The mutant transcript was overrepresented compared to the normal transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7884000" 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>.0009 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886039351 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039351;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=rs886039351" 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=rs886039351" 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=RCV000255995 OR RCV001375937 OR RCV002282092 OR RCV004529455" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000255995, RCV001375937, RCV002282092, RCV004529455" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000255995...</a>
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<p>In a 37-year-old Caucasian patient with autosomal dominant cutis laxa (<a href="/entry/123700">123700</a>), <a href="#33" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Hurst, J., Ashcroft, G. S., Kielty, C., Wilmot, C., Donnai, D., Read, A. P., Jones, C. J. P. <strong>An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa.</strong> Hum. Molec. Genet. 7: 1021-1028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9580666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9580666</a>] [<a href="https://doi.org/10.1093/hmg/7.6.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9580666">Tassabehji et al. (1998)</a> identified heterozygosity for a frameshift mutation in exon 32 of the elastin gene which was predicted to replace 37 amino acids at the C terminus of elastin by a novel sequence of 62 amino acids. Immunoprecipitation studies and mRNA showed that the mutant allele was expressed. Electron microscopy of the skin sections showed abnormal branching and fragmentation in the amorphous elastin component, and immunocytochemistry showed reduced elastin deposition in the elastic fibers and fewer microfibrils in the dermis. These findings suggested that the mutant tropoelastin protein was synthesized, secreted, and incorporated into the elastic matrix, where it altered the architecture of elastic fibers. Interference with crosslinking would reduce elastic recoil in affected tissues and explain the cutis laxa phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9580666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018212 OR RCV002513096" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018212, RCV002513096" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018212...</a>
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<p>In a 30-year-old woman and her 2-year-old son, both of whom had classic cutis laxa (<a href="/entry/123700">123700</a>), <a href="#44" class="mim-tip-reference" title="Zhang, M.-C., He, L., Giro, M., Yong, S. L., Tiller, G. E., Davidson, J. M. <strong>Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN).</strong> J. Biol. Chem. 274: 981-986, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9873040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9873040</a>] [<a href="https://doi.org/10.1074/jbc.274.2.981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9873040">Zhang et al. (1999)</a> identified heterozygosity for a deletion of 2039C from exon 30 of the ELN gene. The same exon was the site of the mutation in the 2012delG deletion (<a href="#0008">130160.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9873040" 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> rs397516433 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397516433;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/rs397516433?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=rs397516433" 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=rs397516433" 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=RCV000036528 OR RCV000199556 OR RCV000624154" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000036528, RCV000199556, RCV000624154" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000036528...</a>
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<p>In 2 large, independently collected midwestern US pedigrees with supravalvular aortic stenosis (<a href="/entry/185500">185500</a>), <a href="#38" class="mim-tip-reference" title="Urban, Z., Michels, V. V., Thibodeau, S. N., Donis-Keller, H., Csiszar, K., Boyd, C. D. <strong>Supravalvular aortic stenosis: a splice site mutation within the elastin gene results in reduced expression of two aberrantly spliced transcripts.</strong> Hum. Genet. 104: 135-142, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10190324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10190324</a>] [<a href="https://doi.org/10.1007/s004390050926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10190324">Urban et al. (1999)</a> found a C-to-G transversion in the acceptor splice site of intron 15 of the elastin gene. The mutation segregated in both families with high penetrance of SVAS, and all affected individuals carried the mutation. Haplotype analysis indicated that the mutations in the 2 apparently nonoverlapping kindreds were identical by descent. RT-PCR of elastin from skin fibroblasts of an affected individual showed 2 abnormal elastin species present as 0.9% and 0.3% of the total elastin message. One transcript arose from activation of a cryptic splice site in intron 15 that added 44 bp of intronic sequence to the sequence encoded by exon 16 and led to a premature termination codon in exon 17 because of frameshift; the other transcript arose from skipping of exon 16. The miniscule amount of transcript associated with this mutation supported haploinsufficiency of elastin as the etiology of SVAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10190324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 SUPRAVALVULAR AORTIC STENOSIS</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">rs1563826213 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1563826213;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=rs1563826213" 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=rs1563826213" 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=RCV000018214 OR RCV001008781" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018214, RCV001008781" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018214...</a>
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<p>In a large German family with SVAS (<a href="/entry/185500">185500</a>), <a href="#2" class="mim-tip-reference" title="Boeckel, T., Dierks, A., Vergopoulos, A., Bahring, S., Knoblauch, H., Muller-Myhsok, B., Baron, H., Aydin, A., Bein, G., Luft, F. C., Schuster, H. <strong>A new mutation in the elastin gene causing supravalvular aortic stenosis.</strong> Am. J. Cardiol. 83: 1141-1143, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10190538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10190538</a>] [<a href="https://doi.org/10.1016/s0002-9149(99)00032-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10190538">Boeckel et al. (1999)</a> identified a 1-bp deletion (1040delC) in codon 347 of exon 18 of the ELN gene, resulting in a stop codon in exon 22. The mutation was present in heterozygous state. The family studied had affected individuals in 4 generations and by implication in a fifth earlier generation. The severity of the phenotype appeared to increase in successive generations, i.e., the phenomenon of anticipation. <a href="#32" class="mim-tip-reference" title="Tassabehji, M., Metcalfe, K., Donnai, D., Hurst, J., Reardon, W., Burch, M., Read, A. P. <strong>Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis.</strong> Hum. Molec. Genet. 6: 1029-1036, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215671</a>] [<a href="https://doi.org/10.1093/hmg/6.7.1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9215671">Tassabehji et al. (1997)</a> noted that the mothers of their severely affected SVAS patients with ELN point mutations had only mild cardiac features or nonpenetrance. <a href="#2" class="mim-tip-reference" title="Boeckel, T., Dierks, A., Vergopoulos, A., Bahring, S., Knoblauch, H., Muller-Myhsok, B., Baron, H., Aydin, A., Bein, G., Luft, F. C., Schuster, H. <strong>A new mutation in the elastin gene causing supravalvular aortic stenosis.</strong> Am. J. Cardiol. 83: 1141-1143, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10190538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10190538</a>] [<a href="https://doi.org/10.1016/s0002-9149(99)00032-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10190538">Boeckel et al. (1999)</a> observed nonpenetrance in at least 2 individuals, brothers, both of whom transmitted the disorder to children. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9215671+10190538" 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 SUPRAVALVULAR AORTIC STENOSIS</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">rs137854454 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137854454;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=rs137854454" 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=rs137854454" 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=RCV000018215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018215</a>
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<p><a href="#22" class="mim-tip-reference" title="Metcalfe, K., Rucka, A. K., Smoot, L., Hofstadler, G., Tuzler, G., McKeown, P., Siu, V., Rauch, A., Dean, J., Dennis, N., Ellis, I., Reardon, W., Cytrynbaum, C., Osborne, L., Yates, J. R., Read, A. P., Donnai, D., Tassabehji, M. <strong>Elastin: mutational spectrum in supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 8: 955-963, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175284</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175284">Metcalfe et al. (2000)</a> identified a tyr150-to-ter (Y150X) mutation in exon 9 of the ELN gene in 4 unrelated patients with SVAS (<a href="/entry/185500">185500</a>) among 100 patients screened. Haplotype analysis using ELN flanking and intragenic markers showed no evidence of a founder effect; therefore this appeared to be a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175284" 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 SUPRAVALVULAR AORTIC STENOSIS</strong>
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ELN, LYS176TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137854455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137854455;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=rs137854455" 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=rs137854455" 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=RCV000018216" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018216" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018216</a>
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<p><a href="#22" class="mim-tip-reference" title="Metcalfe, K., Rucka, A. K., Smoot, L., Hofstadler, G., Tuzler, G., McKeown, P., Siu, V., Rauch, A., Dean, J., Dennis, N., Ellis, I., Reardon, W., Cytrynbaum, C., Osborne, L., Yates, J. R., Read, A. P., Donnai, D., Tassabehji, M. <strong>Elastin: mutational spectrum in supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 8: 955-963, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175284</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175284">Metcalfe et al. (2000)</a> detected a lys176-to-ter (K176X; 526A-T) mutation in exon 10 of the ELN gene in 2 apparently unrelated familial cases of SVAS (<a href="/entry/185500">185500</a>) among 100 patients screened. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175284" 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 SUPRAVALVULAR AORTIC STENOSIS</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">rs2131923188 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2131923188;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=rs2131923188" 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=rs2131923188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2132323982 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2132323982;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=rs2132323982" 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=rs2132323982" 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=RCV000018217 OR RCV001561045 OR RCV001754635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018217, RCV001561045, RCV001754635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018217...</a>
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<p>In 2 related families with supravalvular aortic stenosis (<a href="/entry/185500">185500</a>), <a href="#40" class="mim-tip-reference" title="Urban, Z., Zhang, J., Davis, E. C., Maeda, G. K., Kumar, A., Stalker, H., Belmont, J. W., Boyd, C. D., Wallace, M. R. <strong>Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene.</strong> Hum. Genet. 109: 512-520, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735026</a>] [<a href="https://doi.org/10.1007/s00439-001-0608-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11735026">Urban et al. (2001)</a> identified 2 ELN mutations located on the same allele: an in-frame duplication of nucleotides 1034-1057 in exon 18, and an 1829G-A change in exon 26 predicted to result in an arg610-to-gln (R610Q) substitution. In 1 family, an individual was identified with a recombination between exons 18 and 26 of the ELN gene. This individual was unaffected and carried the exon 18 insertion mutation but not 1829G-A. Skin fibroblasts were established from this recombinant normal individual and from an affected individual carrying both of the mutations. RT-PCR analysis indicated that the expression of the mutant allele was reduced to 12 to 27% of that of the normal allele in the affected but not in the unaffected individual. Further studies showed reduced steady-state elastin mRNA levels and tropoelastin synthesis in the affected individual. RT-PCR analysis of the mRNA rescued by cycloheximide treatment indicated that the 1829G-A mutation created a cryptic donor splice site within exon 26, resulting in the deletion of 4 nucleotides at the 3-prime end of exon 26 and a frameshift in the mRNA. This frameshift mutation generated a premature termination codon in the domain encoded by exon 28, clearly resulting in nonsense-mediated decay of this frameshift RNA product. Despite considerable variability in the molecular nature of mutations responsible for SVAS, the unifying mechanism appears to be the generation of null alleles by nonsense-mediated decay leading to elastin haploinsufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735026" 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>.0016 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018218" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018218" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018218</a>
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<p>In a mother and daughter with cutis laxa (<a href="/entry/123700">123700</a>) and severe pulmonary disease, originally described by <a href="#1" class="mim-tip-reference" title="Beighton, P. H. <strong>The dominant and recessive forms of cutis laxa.</strong> J. Med. Genet. 9: 216-221, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5046633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5046633</a>] [<a href="https://doi.org/10.1136/jmg.9.2.216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5046633">Beighton (1972)</a> and <a href="#3" class="mim-tip-reference" title="Corbett, E., Glaisyer, H., Chan, C., Madden, B., Khaghani, A., Yacoub, M. <strong>Congenital cutis laxa with a dominant inheritance and early onset emphysema.</strong> Thorax 49: 836-837, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8091333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8091333</a>] [<a href="https://doi.org/10.1136/thx.49.8.836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8091333">Corbett et al. (1994)</a>, <a href="#36" class="mim-tip-reference" title="Urban, Z., Gao, J., Pope, F. M., Davis, E. C. <strong>Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin.</strong> J. Invest. Derm. 124: 1193-1199, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15955094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15955094</a>] [<a href="https://doi.org/10.1111/j.0022-202X.2005.23758.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15955094">Urban et al. (2005)</a> identified no mutations in the elastin gene by direct sequencing, but detected an abnormal protein in cultured dermal fibroblasts using metabolic labeling and immunoprecipitation. Mutation and gene expression analyses established the presence of a heterozygous complex rearrangement involving the duplication of exons 9 to 33, with a third copy of exons 9 and 10 and intron 10 added to the end of the mRNA; nucleotides 3-65 of intron 10 encode a 21-amino acid missense peptide sequence before ending in a stop codon. Immunoprecipitation experiments revealed that the mutant tropoelastin is partially secreted and partially retained intracellularly; a polyclonal antibody raised against a unique peptide in the mutant molecule showed both intracellular and matrix staining. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5046633+15955094+8091333" 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>.0017 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018219" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018219" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018219</a>
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<p>In affected members of a 3-generation family of Japanese and German ancestry with cutis laxa (<a href="/entry/123700">123700</a>) and aortic aneurysmal disease, <a href="#31" class="mim-tip-reference" title="Szabo, Z., Crepeau, M. W., Mitchell, A. L., Stephan, M. J., Puntel, R. A., Loke, K. Y., Kirk, R. C., Urban, Z. <strong>Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. (Letter)</strong> J. Med. Genet. 43: 255-258, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16085695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16085695</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16085695[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.034157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16085695">Szabo et al. (2006)</a> identified heterozygosity for a 25-bp deletion beginning at nucleotide 2114 in exon 30 of the ELN gene. There was variable expression of cutis laxa, hernias, and aortic lesions in affected family members. The mutation was not found in 121 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16085695" 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=RCV000018220" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018220" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018220</a>
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<p>In a Singaporean girl of Chinese descent with cutis laxa (<a href="/entry/123700">123700</a>) and aortic aneurysmal disease, <a href="#31" class="mim-tip-reference" title="Szabo, Z., Crepeau, M. W., Mitchell, A. L., Stephan, M. J., Puntel, R. A., Loke, K. Y., Kirk, R. C., Urban, Z. <strong>Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. (Letter)</strong> J. Med. Genet. 43: 255-258, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16085695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16085695</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16085695[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.034157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16085695">Szabo et al. (2006)</a> identified heterozygosity for a de novo 1-bp deletion (2159delC) in exon 30 of the ELN gene. The mutation was not found in either of her parents or in 121 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16085695" 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=RCV000018207 OR RCV000018221 OR RCV000198624 OR RCV004532381" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018207, RCV000018221, RCV000198624, RCV004532381" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018207...</a>
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<p>In a boy with severe cutis laxa (<a href="/entry/123700">123700</a>), severe congenital pulmonary disease (previously not reported in ADCL), and supravalvular pulmonary artery stenosis, <a href="#13" class="mim-tip-reference" title="Graul-Neumann, L. M., Hausser, I., Essayie, M., Rauch, A., Kraus, C. <strong>Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene.</strong> Am. J. Med. Genet. 146A: 977-983, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348261</a>] [<a href="https://doi.org/10.1002/ajmg.a.32242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348261">Graul-Neumann et al. (2008)</a> identified a heterozygous 1621C-T transition in the ELN gene, resulting in an in-frame deletion of exon 25 and predicting a protein lacking amino acids 527-540. The same mutation was present in the clinically healthy father, but not in the mother, the paternal grandparents, or 96 healthy controls. Analysis of ELN expression in fibroblasts revealed the same amount of complete ELN mRNA in the proband as in normal age-matched controls, whereas the father had a more than 50% reduction of ELN mRNA expression as compared to corresponding age-matched controls. In contrast, addition of the translation inhibitor puromcin caused an increase in total ELN mRNA expression in the father. <a href="#13" class="mim-tip-reference" title="Graul-Neumann, L. M., Hausser, I., Essayie, M., Rauch, A., Kraus, C. <strong>Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene.</strong> Am. J. Med. Genet. 146A: 977-983, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348261</a>] [<a href="https://doi.org/10.1002/ajmg.a.32242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348261">Graul-Neumann et al. (2008)</a> concluded that the variable processing of an identically mutated gene (dominant negative in the child and haploinsufficiency in the father) caused the highly variable clinical appearance of ADCL in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348261" 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>.0020 SUPRAVALVULAR AORTIC STENOSIS</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">rs1554686162 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554686162;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=rs1554686162" 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=rs1554686162" 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=RCV000022536" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022536" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022536</a>
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<p>In a 3-generation family with supravalvular aortic stenosis (SVAS; <a href="/entry/185500">185500</a>), <a href="#23" class="mim-tip-reference" title="Micale, L., Turturo, M. G., Fusco, C., Augello, B., Jurado, L. A. P., Izzi, C., Digilio, M. C., Milani, D., Lapi, E., Zelante, L., Merla, G. <strong>Identification and characterization of seven novel mutations of elastin gene in a cohort of patients affected by supravalvular aortic stenosis.</strong> Europ. J. Hum. Genet. 18: 317-323, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19844261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19844261</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19844261[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/10.1038/ejhg.2009.181" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19844261">Micale et al. (2010)</a> identified a heterozygous 2044+5G-C transversion in intron 28 of the ELN gene. The mutation was present in all 3 family members who had been diagnosed with SVAS as well as in 1 asymptomatic family member; it was not found in 2 more unaffected family members or in 100 unrelated control samples. RT-PCR analysis of elastin mRNA from transfected HEK293 cells as well as patient fibroblasts demonstrated 2 distinct transcripts, a 200-bp band corresponding to wildtype mRNA product and a 300-bp mutant; sequencing confirmed that the longer transcript resulted from splicing failure and inclusion of intron 28 in the mRNA, predicting a shorter elastin protein with a premature termination codon within the same intron. Assessment of ELN mRNA expression level after incubation of patient fibroblasts with an inhibitor of nonsense-mediated decay (NMD) showed no significant increase in ELN mRNA aberrant transcript, indicating that this mutation is conceivably not a substrate of NMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19844261" 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="#Reidy1963" class="mim-tip-reference" title="Reidy, J. P. <strong>Cutis hyperelastica (Ehlers-Danlos) and cutis laxa.</strong> Brit. J. Plast. Surg. 16: 84-94, 1963.">Reidy (1963)</a>; <a href="#Sephel1989" class="mim-tip-reference" title="Sephel, G. C., Byers, P. H., Holbrook, K. A., Davidson, J. M. <strong>Heterogeneity of elastin expression in cutis laxa fibroblast strains.</strong> J. Invest. Derm. 93: 147-153, 1989.">Sephel et al. (1989)</a>
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<strong>The dominant and recessive forms of cutis laxa.</strong>
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J. Med. Genet. 9: 216-221, 1972.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5046633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5046633</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5046633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.9.2.216" target="_blank">Full Text</a>]
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Boeckel, T., Dierks, A., Vergopoulos, A., Bahring, S., Knoblauch, H., Muller-Myhsok, B., Baron, H., Aydin, A., Bein, G., Luft, F. C., Schuster, H.
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<strong>A new mutation in the elastin gene causing supravalvular aortic stenosis.</strong>
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Am. J. Cardiol. 83: 1141-1143, 1999.
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[<a href="https://doi.org/10.1016/s0002-9149(99)00032-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/thx.49.8.836" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0092-8674(93)90168-p" target="_blank">Full Text</a>]
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<strong>The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome.</strong>
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[<a href="https://doi.org/10.1038/sj.ejhg.5200812" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI117057" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng0993-11" target="_blank">Full Text</a>]
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<strong>A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.</strong>
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[<a href="https://doi.org/10.1073/pnas.90.8.3226" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI19028" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1469-1809.1993.tb00890.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32242" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/CIRCRESAHA.107.153510" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.84.16.5680" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.3109/03008208709006976" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s00431-002-1111-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nm1583" target="_blank">Full Text</a>]
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<a id="36" class="mim-anchor"></a>
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<a id="Urban2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urban, Z., Gao, J., Pope, F. M., Davis, E. C.
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<strong>Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin.</strong>
|
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J. Invest. Derm. 124: 1193-1199, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15955094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15955094</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15955094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.0022-202X.2005.23758.x" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="37" class="mim-anchor"></a>
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<a id="Urban2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urban, Z., Michels, V. V., Thibodeau, S. N., Davis, E. C., Bonnefont, J.-P., Munnich, A., Eyskens, B., Gewillig, M., Devriendt, K., Boyd, C. D.
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<strong>Isolated supravalvular aortic stenosis: functional haploinsufficiency of the elastin gene as a result of nonsense-mediated decay.</strong>
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Hum. Genet. 106: 577-588, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004390000285" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="38" class="mim-anchor"></a>
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<a id="Urban1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urban, Z., Michels, V. V., Thibodeau, S. N., Donis-Keller, H., Csiszar, K., Boyd, C. D.
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<strong>Supravalvular aortic stenosis: a splice site mutation within the elastin gene results in reduced expression of two aberrantly spliced transcripts.</strong>
|
|
Hum. Genet. 104: 135-142, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10190324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10190324</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10190324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004390050926" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="39" class="mim-anchor"></a>
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<a id="Urban2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urban, Z., Riazi, S., Seidl, T. L., Katahira, J., Smoot, L. B., Chitayat, D., Boyd, C. D., Hinek, A.
|
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<strong>Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome.</strong>
|
|
Am. J. Hum. Genet. 71: 30-44, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12016585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12016585</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12016585[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=12016585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/341035" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="40" class="mim-anchor"></a>
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<a id="Urban2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Urban, Z., Zhang, J., Davis, E. C., Maeda, G. K., Kumar, A., Stalker, H., Belmont, J. W., Boyd, C. D., Wallace, M. R.
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<strong>Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene.</strong>
|
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Hum. Genet. 109: 512-520, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-001-0608-z" 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="41" class="mim-anchor"></a>
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<a id="Wydner1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wydner, K. S., Sechler, J. L., Boyd, C. D., Passmore, H. C.
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<strong>Use of an intron length polymorphism to localize the tropoelastin gene to mouse chromosome 5 in a region of linkage conservation with human chromosome 7.</strong>
|
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Genomics 23: 125-131, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7829060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7829060</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829060" 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/10.1006/geno.1994.1467" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="42" class="mim-anchor"></a>
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<a id="Zhang1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, M. C., He, L., Yong, S. L., Tiller, G. E., Davidson, J. M.
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<strong>Cutis laxa arising from a frame shift mutation in the elastin gene (ELN). (Abstract)</strong>
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Am. J. Hum. Genet. 61 (suppl.): A353 only, 1997.
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<li>
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<a id="43" class="mim-anchor"></a>
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<a id="Zhang1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, M.-C., Giro, M., Quaglino, D., Jr., Davidson, J. M.
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<strong>Transforming growth factor-beta reverses a posttranscriptional defect in elastin synthesis in a cutis laxa skin fibroblast strain.</strong>
|
|
J. Clin. Invest. 95: 986-994, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7884000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7884000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7884000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI117808" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="44" class="mim-anchor"></a>
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<a id="Zhang1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, M.-C., He, L., Giro, M., Yong, S. L., Tiller, G. E., Davidson, J. M.
|
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<strong>Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN).</strong>
|
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J. Biol. Chem. 274: 981-986, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9873040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9873040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9873040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.274.2.981" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 3/14/2012
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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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Kelly A. Przylepa - updated : 11/20/2008<br>Patricia A. Hartz - updated : 5/1/2008<br>Paul J. Converse - updated : 6/11/2007<br>Marla J. F. O'Neill - updated : 4/19/2006<br>Victor A. McKusick - updated : 5/10/2004<br>Natalie E. Krasikov - updated : 2/19/2004<br>Michael B. Petersen - updated : 2/11/2003<br>Victor A. McKusick - updated : 7/17/2002<br>Victor A. McKusick - updated : 12/6/2001<br>Michael B. Petersen - updated : 4/17/2001<br>Victor A. McKusick - updated : 8/16/2000<br>Victor A. McKusick - updated : 5/14/1999<br>Ada Hamosh - updated : 3/18/1999<br>Victor A. McKusick - updated : 1/5/1999<br>Victor A. McKusick - updated : 12/1/1998<br>Victor A. McKusick - updated : 6/19/1998<br>Victor A. McKusick - updated : 6/15/1998<br>Victor A. McKusick - updated : 10/24/1997<br>Victor A. McKusick - updated : 8/15/1997<br>Moyra Smith - updated : 10/21/1996
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/12/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/11/2023<br>carol : 01/10/2020<br>carol : 09/30/2014<br>carol : 3/15/2012<br>terry : 3/14/2012<br>alopez : 1/26/2012<br>alopez : 1/24/2012<br>carol : 9/1/2010<br>wwang : 8/25/2010<br>ckniffin : 8/16/2010<br>carol : 8/9/2010<br>alopez : 1/6/2010<br>carol : 11/26/2008<br>terry : 11/20/2008<br>wwang : 10/14/2008<br>terry : 9/25/2008<br>mgross : 5/1/2008<br>mgross : 6/11/2007<br>mgross : 6/11/2007<br>carol : 4/20/2006<br>carol : 4/19/2006<br>terry : 4/19/2006<br>tkritzer : 5/26/2004<br>terry : 5/10/2004<br>carol : 2/19/2004<br>terry : 2/19/2004<br>cwells : 2/11/2003<br>tkritzer : 7/29/2002<br>tkritzer : 7/26/2002<br>terry : 7/17/2002<br>carol : 1/2/2002<br>mcapotos : 12/13/2001<br>terry : 12/6/2001<br>carol : 5/18/2001<br>mcapotos : 5/10/2001<br>mcapotos : 4/17/2001<br>carol : 8/29/2000<br>terry : 8/16/2000<br>carol : 3/15/2000<br>mgross : 5/25/1999<br>mgross : 5/18/1999<br>terry : 5/14/1999<br>alopez : 3/19/1999<br>alopez : 3/18/1999<br>mgross : 3/17/1999<br>carol : 1/6/1999<br>carol : 1/6/1999<br>terry : 1/5/1999<br>carol : 12/2/1998<br>terry : 12/1/1998<br>terry : 8/11/1998<br>carol : 6/22/1998<br>terry : 6/19/1998<br>alopez : 6/18/1998<br>terry : 6/15/1998<br>terry : 5/29/1998<br>terry : 10/28/1997<br>alopez : 10/27/1997<br>terry : 10/24/1997<br>mark : 10/6/1997<br>mark : 9/9/1997<br>mark : 8/19/1997<br>jenny : 8/19/1997<br>terry : 8/15/1997<br>mark : 1/29/1997<br>mark : 10/21/1996<br>mark : 10/21/1996<br>mark : 11/6/1995<br>terry : 11/7/1994<br>mimadm : 9/24/1994<br>jason : 6/8/1994<br>warfield : 4/8/1994<br>pfoster : 4/1/1994
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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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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 130160
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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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ELASTIN; ELN
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ELN</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>SNOMEDCT:</strong> 268185002;
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<strong>ICD10CM:</strong> Q25.3;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 7q11.23
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:74,028,173-74,069,907 </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="2">
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<span class="mim-font">
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7q11.23
|
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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
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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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123700
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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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Supravalvar aortic stenosis
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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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185500
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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">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Elastic fibers are composed of 2 distinct components, a more abundant amorphous component (elastin) and the microfibrillar component. Elastin is composed largely of glycine, proline, and other hydrophobic residues and contains multiple lysine-derived crosslinks, such as desmosines, which link the individual polypeptide chains into a rubberlike network. The hydrophobic regions of the chains between the crosslinks are highly mobile. The hydrophobic and crosslinking domains are coded by separate, small (27 to 114 bp) exons that are separated by large introns. The initial translation product is a 72-kD polypeptide, designated tropoelastin (Rosenbloom, 1984). </p><p>Indik et al. (1987) cloned human elastin cDNA and found that it encodes a deduced 786-amino acid protein. They described alternative splicing of elastin mRNA. </p><p>Uitto et al. (1991) reviewed the molecular biology of human elastin. Elastin is initially synthesized as a soluble polypeptide of approximately 72 kD. The individual elastin molecules are aligned on a scaffolding of microfibrils composed of fibrillin (134797). This alignment is stabilized by the formation of intermolecular crosslinks known as desmosines, which contribute to the insolubility of elastin. Formation of desmosines is initiated by oxidative deamination of certain lysyl residues by lysyl oxidase, a copper-dependent enzyme. The elastin polypeptides are encoded by an mRNA of approximately 3.5 kb which comprises a 2.2-kb coding segment and a relatively large 1.3-kb, 3-prime untranslated region. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Emanuel et al. (1985) provisionally assigned the elastin gene to 2q31-qter. Fazio et al. (1991) used human elastin cDNAs in both in situ hybridization and Southern analysis of human-rodent cell hybrids to map the elastin gene to 7q11.2. PCR analysis with elastin-specific primers of DNA from a hybrid cell line containing only human chromosome 7 yielded a product of the expected size, while DNA containing human chromosome 2, but not chromosome 7, did not result in a product. Foster et al. (1993) described a dinucleotide repeat polymorphism in the ELN gene and used it to confirm assignment to chromosome 7 as well as to exclude the gene from chromosome 2 by linkage studies. </p><p>Wydner et al. (1994) used PCR primers complementary to regions of the mouse tropoelastin mRNA to define a novel intron length polymorphism (ILP) within intron 8 of the mouse elastin gene. Using this polymorphism in an interspecific backcross, they mapped the mouse Eln gene to the distal half of chromosome 5 in a region of homology of synteny of human chromosome 7. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Indik et al. (1987) found a dearth of coding sequences and a remarkable abundance of Alu repetitive sequences in the 3-prime region of the human elastin gene. This suggested to them that, mediated by recombination between Alu sequences, considerable polymorphism may exist in the human population and between species. Tromp et al. (1991) identified a RFLP in the ELN gene. </p><p>The human ELN gene has 34 exons and spans a total of approximately 45 kb of genomic DNA. The exon/intron ratio is unusually low, approximately 1:19 (Uitto et al., 1991). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Li et al. (1998) defined the role of elastin in arterial development and disease by generating mice lacking elastin. These mice died of an obstructive arterial disease that resulted from subendothelial cell proliferation and reorganization of smooth muscle. These cellular changes were similar to those seen in atherosclerosis; however, lack of elastin was not associated with endothelial damage, thrombosis, or inflammation, which occur in models of atherosclerosis. Hemodynamic stress was not associated with arterial obstruction in these mice either, as the disease still occurred in arteries that were isolated in organ culture and therefore not subject to hemodynamic stress. Disruption of elastin was enough to induce subendothelial proliferation of smooth muscle and may contribute to obstructive arterial disease. </p><p>To investigate why a loss-of-function mutation in 1 elastin allele causes an inherited obstructive arterial disease, supravalvular aortic stenosis, Li et al. (1998) generated mice hemizygous for the elastin gene (Eln +/-). Although ELN mRNA and protein were reduced by 50% in Eln +/- mice, arterial compliance at physiologic pressures was nearly normal. This discrepancy was explained by a paradoxical increase of 35% in the number of elastic lamellae and smooth muscle in Eln +/- arteries. Examination of humans with ELN hemizygosity revealed a 2.5-fold increase in elastic lamellae and smooth muscle. Thus, ELN hemizygosity in mice and humans induces a compensatory increase in the number of rings of elastic lamellae and smooth muscle during arterial development. Humans are exquisitely sensitive to reduced ELN expression, developing profound arterial thickening and markedly increased risk of obstructive vascular disease. </p><p>Lee et al. (2007) studied the immune responses of age-matched smokers with and without emphysema (see COPD; 606963) and found that differential responsiveness of T cells to elastin peptides, but not to collagen (see COL6A1; 120220) or albumin (ALB; 103600), correlated with emphysema severity. Compared with controls, COPD patients secreted increased levels of IFNG (147570) and IL10 (124092) in response to elastin peptides in an MHC II-dependent manner. Antibody to elastin, but not to collagen, was also increased in emphysema patients, as were lung B cells secreting antibody to the protein. Although regulatory T cell (Treg) responses did not differ between subject and control peripheral blood cells, emphysema patients showed a significant reduction of lung Tregs compared with controls. Lee et al. (2007) concluded that antielastin autoimmunity, possibly resulting from secretion of proteolytic enzymes induced by cigarette smoke exposure, is associated with an inflammatory response leading to emphysema and to tobacco-related pathology in other organs. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Role in Williams-Beuren Syndrome</em></strong></p><p>
|
|
Curran et al. (1993) showed that the ELN gene was disrupted in a translocation with a breakpoint at 7q11.23. Exon 28 of the gene was the site of the breakpoint. Furthermore, Ewart et al. (1993) showed close linkage of ELN and supravalvular aortic stenosis (SVAS; 185500) in 2 families. Ewart et al. (1993) found that deletion involving 7q11.23 and resulting in hemizygosity of the elastin gene is responsible for the Williams-Beuren syndrome (WBS; 194050). Deletions limited to the elastin gene appear to result in SVAS, whereas deletions spanning at least 114 kb lead to the Williams syndrome. Thus, the latter is a contiguous gene syndrome with neurobehavioral features and mental retardation not easily accounted for by the disruption of the elastin gene alone. </p><p>Perez Jurado et al. (1996) reported that 61 of 65 clinically defined patients with Williams-Beuren syndrome had a deletion of the ELN locus. They noted that no variability in the size of the deletion could be detected between WBS patients by genotyping of polymorphic markers, suggesting that the chromosomal breakpoints in these patients fell into narrowly defined physical regions. Perez Jurado et al. (1996) also compared clinical differences between maternally and paternally inherited ELN deletions and postulated that an imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion. </p><p>Duba et al. (2002) investigated a family with a cytogenetically balanced translocation t(7;16)(q11.23;q13) in which the 5 translocation carriers manifested a wide variation in phenotype, ranging from a hoarse voice as the only feature, partial WBS with or without SVAS, to the full WBS phenotype. DNA sequence analysis showed that the breakpoint on chromosome 7 was within intron 5 of the ELN gene and on chromosome 16 within intron 1 of the GPR56 gene (604110). In the course of the rearrangement, no basepair was lost from either the chromosome 7 or chromosome 16 sequences. Duba et al. (2002) speculated that the expected phenotype in the reported family would be SVAS, not WBS, and proposed a long-range position effect caused by the translocation event as the most likely explanation. </p><p><strong><em>Supravalvular Aortic Stenosis</em></strong></p><p>
|
|
In a family with SVAS (185500), Ewart et al. (1994) found, by pulsed field, PCR, and Southern analysis, a 100-kb deletion of the 3-prime end of the elastin gene cosegregating with the disease (130160.0001). DNA sequence analysis localized the breakpoint of the deletion between elastin exons 27 and 28, the same region disrupted by the SVAS-associated translocation. The family included an affected mother and daughter. The daughter had right ventricular hypertrophy, supravalvular pulmonic stenosis, bilateral narrowing of the pulmonary arteries (left more severe than right), and a diffusely narrowed ascending aorta with a discrete supravalvular narrowing diagnosed by cardiac catheterization at 6 weeks of age. The patient also had intermittent acrocyanosis and hypertension. At 16 months of age, the supravalvular pulmonic stenosis had improved. The proband also had some features common to Williams syndrome, including dolichocephaly, bitemporal narrowness, outer canthal distance less than 2 SD below the mean, periorbital fullness, broad mouth, full cheeks, hoarse voice, and hypersensitivity to loud noises. The diagnosis of Williams syndrome was not made because she had normal serum calcium levels, a normal urine calcium/creatinine ratio, normal psychomotor development, and normal growth parameters. The child was treated with phenobarbital for seizures. The mother had had seizures in adolescence. Since childhood, she had had a grade III (out of VI) early systolic murmur heard best at the suprasternal notch and radiating to the left carotid. At least 2 other family members were affected by SVAS. The mother's brother had narrowing of the entire pulmonary arterial tree documented by cardiac catheterization and was treated for seizures. A maternal first cousin had severe bilateral peripheral pulmonic stenosis, right ventricular hypertrophy, and mild SVAS demonstrated by echocardiogram. </p><p>Gross rearrangements of the ELN gene have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for SVAS, Li et al. (1997) refined the genomic structure of the gene and used this information in mutation analyses. ELN point mutations were found to cosegregate with the disease in 4 familial cases (e.g., 130160.0005) and to be associated with SVAS in 3 sporadic cases (130160.0004). Two of the mutations were nonsense, 1 was a single bp deletion, and 4 were splice site mutations. In 1 sporadic case, the mutation had arisen de novo. </p><p>Tassabehji et al. (1997) described the complete exon-intron structure of the ELN gene. All exons are in-frame, allowing exon skipping without disrupting the reading frame. Microsatellites were located in introns 17 and 18. They found that isolated SVAS was associated with point mutations that predicted premature chain termination. They stated that in their experience all patients with a classic Williams syndrome phenotype had been found to be hemizygous at the elastin locus; nevertheless, only 5% had severe clinical SVAS. In their 2 SVAS families with point mutations, each mutation manifested as severe SVAS in the proband, but as mild cardiac features or nonpenetrance in the mothers. Tassabehji et al. (1997) considered such variability typical of phenotypes produced by haploinsufficiency, where genetic background is expected to have a major modifying effect. An alternative hypothesis is that a dominant-negative elastin mutation results if truncated proteins have some, but not all, domains critical for intermolecular interactions and thus may disrupt posttranslational processing and development of elastic fibers. </p><p>Koch et al. (2003) similarly found the complete spectrum of arterial stenoses in 5 members of an extended pedigree with a confirmed nonsense mutation haplotype. </p><p>Urban et al. (2000) used single-strand conformation and heteroduplex analyses of genomic amplimers to identify point mutations within the ELN gene in patients with nonsyndromic SVAS from a total of 8 unrelated families. They identified 6 novel point mutations. Nonpenetrance was demonstrated in some of the families. Together with the new mutations they found, 14 point mutations had been reported in SVAS patients, and 10 of these resulted in premature stop codons (PTCs). They analyzed the expression of ELN alleles in skin fibroblasts from 1 SVAS patient and showed that PTC mutations resulted in selective elimination of mutant transcripts. Inhibition of the nonsense-mediated decay mechanism by cycloheximide resulted in the stabilization of mutant elastin mRNA. Allelic inactivation by the ELN mutation in this patient led to an overall decrease of the steady-state levels of elastin mRNA. In the skin fibroblasts from the same SVAS patient, they demonstrated reduced synthesis and secretion of tropoelastin. Given the predominance of PTC mutations in SVAS, Urban et al. (2000) suggested that functional haploinsufficiency may be the pathomechanism underlying most cases of nonsyndromic SVAS. </p><p>Metcalfe et al. (2000) used SSCP and heteroduplex analysis to screen 100 unrelated patients with SVAS and normal karyotypes without major deletions of the ELN gene as determined by FISH. All 34 exons of the ELN gene were screened and mutations were identified in 35 of the patients. The mutations were 23 nonsense or frameshift mutations predicted to cause premature termination, 6 splice site mutations, 4 missense mutations, and 2 small deletions in exon 1 encompassing the ATG initiation codon. The 35 patients represented 24 familial cases, 10 sporadic cases, and 1 of unknown status. Recurrent mutations were the nonsense mutations Y150X in exon 9 (130160.0013), Q442X in exon 21 (130160.0003), and K176X in exon 10 (130160.0014), which appeared to be mutation hotspots. A marked phenotypic intrafamilial variability was illustrated by 2 large families with multiple affected members with disease severity ranging from asymptomatic carriers to mild or severe SVAS requiring surgery, or sudden infant death. No obvious genotype-phenotype correlation was detected; cases with missense or splicing mutations were as likely to have severe SVAS as cases with truncating mutations. </p><p>Urban et al. (2002) compared both elastogenesis and proliferation rate of cultured aortic smooth-muscle cells (SMCs) and skin fibroblasts from 5 healthy control subjects, 4 patients with isolated SVAS, and 5 patients with WBS. Three mutations found in patients with SVAS were found to result in null alleles. RNA blood hybridization, immunostaining, and metabolic labeling experiments demonstrated that SVAS cells and WBS cells have reduced elastin mRNA levels and that they consequently deposit low amounts of insoluble elastin. Abnormally low levels of elastin deposition in SVAS cells and in WBS cells were found to coincide with an increase in proliferation rate, which could be reversed by addition of exogenous insoluble elastin. This led to the conclusion that insoluble elastin is an important regulator of cellular proliferation. The reduced net deposition of insoluble elastin in arterial walls of patients with either SVAS or WBS leads to the increased proliferation of arterial SMCs, which results in the formation of multilayer thickening of the tunica media of large arteries and, consequently, in the development of hyperplastic intimal lesions leading to segmental arterial occlusion. </p><p>Micale et al. (2010) analyzed the ELN gene in 31 familial and sporadic cases of SVAS and identified 7 novel mutations, including 5 frameshift mutations and 2 splice site mutations (see, e.g., 130160.0020). In vitro analysis of 3 of the frameshift mutations using minigene constructs and transfection assays confirmed that functional haploinsufficiency of the ELN gene is the main pathomechanism underlying SVAS. In addition, molecular analysis of patient fibroblasts showed that the 2044+5G-C (130160.0020) mutant allele encodes an aberrant shorter form of the elastin polypeptide that may hamper the normal assembly of elastin fibers in a dominant-negative manner. </p><p><strong><em>Cutis Laxa</em></strong></p><p>
|
|
In the cell line from a patient with cutis laxa (123700), Zhang et al. (1997) identified heterozygosity for a 1-bp deletion in exon 30 of the ELN gene (130160.0008). In a 30-year-old woman and her 2-year-old son, both of whom had classic cutis laxa, Zhang et al. (1999) identified heterozygosity for a different 1-bp deletion in the ELN gene (130160.0010), also in exon 30. </p><p>In a 37-year-old Caucasian woman with cutis laxa, Tassabehji et al. (1998) identified heterozygosity for a 1-bp deletion in the ELN gene (130160.0009). </p><p>In a mother and daughter with cutis laxa and severe pulmonary disease, originally described by Beighton (1972) and Corbett et al. (1994), Urban et al. (2005) identified no mutations in the elastin gene by direct sequencing, but detected an abnormal protein in cultured dermal fibroblasts using metabolic labeling and immunoprecipitation. Mutation and gene expression analyses established the presence of a complex tandem duplication in the elastin gene (130160.0016). </p><p>In affected members of a 3-generation family of Japanese and German ancestry and an unrelated Singaporean girl of Chinese descent with cutis laxa and aortic aneurysmal disease, Szabo et al. (2006) identified heterozygosity for a 25-bp deletion (130160.0017) and a 1-bp deletion (130160.0018) in exon 30 of the ELN gene, respectively. </p><p><strong><em>Role in Other Disorders</em></strong></p><p>
|
|
For a discussion of a possible association between variation in the ELN gene and susceptibility to intracranial berry aneurysm, see ANIB1 (105800).</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">
|
|
<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>Faury et al. (2003) reported that Eln +/- mice were stably hypertensive from birth, with a mean arterial pressure 25 to 30 mm Hg higher than their wildtype counterparts. The animals had only moderate cardiac hypertrophy and lived a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln +/- arteries were generally smaller than wildtype arteries at any given intravascular pressure. Because the Eln +/- mice were hypertensive, however, the effective arterial working diameter was comparable to that of the normotensive wildtype animal. Physiologic studies indicated a role for the renin (179820)-angiotensin (see 106150) system in maintaining the hypertensive state. Faury et al. (2003) concluded that the association of hypertension with elastin haploinsufficiency in humans and mice strongly suggested that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension. </p><p>Hirano et al. (2007) stated that the Eln gene in most mammalian species contains 36 exons. The rat and mouse Eln genes have 37 exons, whereas the human ELN gene has only 34 exons due to the sequential loss of 2 exons during primate evolution. In addition, although still contained within the human gene, exon 22 is rarely included in the elastin transcript. The mouse and human ELN proteins share only 64.1% amino acid identity. Because of the structural differences between mouse and human ELN, Hirano et al. (2007) developed a humanized elastin mouse in which elastin production was controlled by a human ELN transgene. Expression of the human transgene reversed the hypertension and cardiovascular changes associated with Eln haploinsufficiency and rescued the perinatal lethality of the Eln-null phenotype. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<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>20 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 SUPRAVALVULAR AORTIC STENOSIS</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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ELN, 100-KB DEL
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<br />
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ClinVar: RCV000018203
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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 family with SVAS (185500), Ewart et al. (1994) found a heterozygous 100-kb deletion in the 3-prime end of the elastin gene with a breakpoint between elastin exons 27 and 28. The same region was disrupted in the familial reciprocal translocation reported by Morris et al. (1993). Ewart et al. (1994) pointed out that the protein product of the mutant gene would lack a microfibril-associated glycoprotein (MAGP; 156790) binding site that normally exists in the C terminus of elastin. </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 SUPRAVALVULAR AORTIC STENOSIS</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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ELN, 30-KB DEL
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<br />
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ClinVar: RCV000018204
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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>Olson et al. (1995) used Southern blot analysis to screen for mutations in the ELN gene in 6 familial and 3 sporadic cases of SVAS (185500) without features of Williams-Beuren syndrome (194050). The familial cases included members of a previously reported large pedigree with linkage to the elastin gene region (Olson et al., 1993). A 30-kb deletion extending from breakpoints in intron 1 and intron 27 was found in 2 members of a Middle Eastern family. The proband developed severe SVAS and peripheral pulmonary artery stenosis and underwent aortic operation in early childhood. He had no evidence of Williams syndrome or clinically apparent abnormalities of other elastin-containing tissue. The deletion was also demonstrated in his mother, an obligate carrier with subtle disease (a heart murmur and a nondiagnostic echocardiogram). Blood for DNA analysis was not available from a maternal uncle with SVAS and a sister with isolated peripheral pulmonary artery stenosis. </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 SUPRAVALVULAR AORTIC STENOSIS</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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ELN, GLN442TER
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<br />
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SNP: rs137854452,
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ClinVar: RCV000018206, RCV000255419
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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>Li et al. (1997) found a heterozygous nonsense mutation in a sporadic case of SVAS (185500): a C-to-T transition at nucleotide 1324, resulting in conversion of a glutamine to a premature stop codon (Q442X) in exon 21. DNA samples could not be obtained from the parents of the proband. </p><p>Tassabehji et al. (1997) found the same mutation in a patient with SVAS. The patient had presented at the age of 8 weeks with a heart murmur and episodes of cyanosis. Echocardiography at 4 months of age showed SVAS and pulmonary arterial stenosis. These changes were progressive. Corrective open heart surgery was performed at the age of 21 months, at which time it was noted that the aorta and pulmonary arteries were very thick and abnormal. His mother had had cardiac follow-up for a heart murmur until the age of 6 years, but echocardiogram showed no evidence of SVAS and no pulmonary artery stenosis. </p><p>Metcalfe et al. (2000) found the Q442X mutation in 3 unrelated patients with SVAS among 100 patients screened. Haplotype analysis using ELN flanking and intragenic markers showed no evidence of a founder effect; therefore this appeared to be a mutation hotspot. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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</div>
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, ARG570TER
|
|
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|
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|
<br />
|
|
|
|
SNP: rs137854453,
|
|
|
|
|
|
gnomAD: rs137854453,
|
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|
|
|
|
ClinVar: RCV000018207, RCV000018221, RCV000198624, RCV004532381
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of SVAS (185500), Li et al. (1997) found a nonsense mutation: a C-to-T transition at nucleotide 1708, resulting in conversion of arginine-570 to a premature stop codon in exon 25 (R570X). DNA samples could not be obtained from the parents of the proband. </p><p>Metcalfe et al. (2000) detected the R570X mutation in a sporadic case of SVAS with peripheral pulmonary artery stenosis and bilateral inguinal hernias. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
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<span class="mim-text-font">
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ELN, 1-BP DEL, 1821C
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<br />
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|
|
ClinVar: RCV000018208
|
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Using primers amplifying exon 26 of the ELN gene, Li et al. (1997) identified an anomalous band that cosegregated with SVAS (185500) in 1 family. The aberrant conformer showed a single-nucleotide deletion at position 1821 in exon 26 (1821delC). This deletion caused a frameshift resulting in a premature stop codon in exon 28. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
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|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, IVS15AS, A-G, -2
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<br />
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|
|
|
SNP: rs727503027,
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|
|
|
|
|
ClinVar: RCV000150636
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated kindreds, Li et al. (1997) found that SVAS (185500) segregated with an A-to-G transition at position -2 in the splice acceptor site of intron 15 preceding exon 16. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, 1-BP INS, FS615TER
|
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|
|
<br />
|
|
|
|
SNP: rs2132322943,
|
|
|
|
|
|
|
|
ClinVar: RCV000018209
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with SVAS (185500), Tassabehji et al. (1997) identified insertion of a T in codon 606 of exon 26 of the ELN gene, producing a frameshift predicted to cause premature termination 10 codons downstream. The patient presented at birth with a heart murmur. At the age of 3 years, echocardiography suggested SVAS on the basis of 'waisting' of the ascending aorta and poststenotic dilatation. A brother had died suddenly in the first year of life and at autopsy was noted to have spontaneously repaired SVAS, repaired central pulmonary artery stenosis, and marked ventricular hypertrophy. The aortic valve and proximal aorta were markedly dysplastic with extreme thickening beyond the valve. The proband's mother had presented to cardiologists in childhood with a murmur and a clinical diagnosis of aortic stenosis had been made. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, 1-BP DEL, 2012G
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs1797225811,
|
|
|
|
|
|
|
|
ClinVar: RCV000018210
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with cutis laxa (123700), Zhang et al. (1995) demonstrated decreased elastin mRNA levels in skin fibroblasts due to transcript instability. Zhang et al. (1997) cloned and sequenced both ELN cDNA alleles in the cell line from this patient and identified a frameshift mutation, deletion of 2012G, in the C-terminal coding region of 1 allele. The patient was heterozygous for the single base deletion, which was not found in genomic DNA from either parent or from 65 unrelated control samples. The mutant transcript was overrepresented compared to the normal transcript. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, 1-BP DEL, 748A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886039351,
|
|
|
|
|
|
|
|
ClinVar: RCV000255995, RCV001375937, RCV002282092, RCV004529455
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 37-year-old Caucasian patient with autosomal dominant cutis laxa (123700), Tassabehji et al. (1998) identified heterozygosity for a frameshift mutation in exon 32 of the elastin gene which was predicted to replace 37 amino acids at the C terminus of elastin by a novel sequence of 62 amino acids. Immunoprecipitation studies and mRNA showed that the mutant allele was expressed. Electron microscopy of the skin sections showed abnormal branching and fragmentation in the amorphous elastin component, and immunocytochemistry showed reduced elastin deposition in the elastic fibers and fewer microfibrils in the dermis. These findings suggested that the mutant tropoelastin protein was synthesized, secreted, and incorporated into the elastic matrix, where it altered the architecture of elastic fibers. Interference with crosslinking would reduce elastic recoil in affected tissues and explain the cutis laxa phenotype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, 1-BP DEL, 2039C
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000018212, RCV002513096
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 30-year-old woman and her 2-year-old son, both of whom had classic cutis laxa (123700), Zhang et al. (1999) identified heterozygosity for a deletion of 2039C from exon 30 of the ELN gene. The same exon was the site of the mutation in the 2012delG deletion (130160.0008). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, IVS15AS, C-G, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397516433,
|
|
|
|
|
|
gnomAD: rs397516433,
|
|
|
|
|
|
ClinVar: RCV000036528, RCV000199556, RCV000624154
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 large, independently collected midwestern US pedigrees with supravalvular aortic stenosis (185500), Urban et al. (1999) found a C-to-G transversion in the acceptor splice site of intron 15 of the elastin gene. The mutation segregated in both families with high penetrance of SVAS, and all affected individuals carried the mutation. Haplotype analysis indicated that the mutations in the 2 apparently nonoverlapping kindreds were identical by descent. RT-PCR of elastin from skin fibroblasts of an affected individual showed 2 abnormal elastin species present as 0.9% and 0.3% of the total elastin message. One transcript arose from activation of a cryptic splice site in intron 15 that added 44 bp of intronic sequence to the sequence encoded by exon 16 and led to a premature termination codon in exon 17 because of frameshift; the other transcript arose from skipping of exon 16. The miniscule amount of transcript associated with this mutation supported haploinsufficiency of elastin as the etiology of SVAS. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, 1-BP DEL, 1040C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1563826213,
|
|
|
|
|
|
|
|
ClinVar: RCV000018214, RCV001008781
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large German family with SVAS (185500), Boeckel et al. (1999) identified a 1-bp deletion (1040delC) in codon 347 of exon 18 of the ELN gene, resulting in a stop codon in exon 22. The mutation was present in heterozygous state. The family studied had affected individuals in 4 generations and by implication in a fifth earlier generation. The severity of the phenotype appeared to increase in successive generations, i.e., the phenomenon of anticipation. Tassabehji et al. (1997) noted that the mothers of their severely affected SVAS patients with ELN point mutations had only mild cardiac features or nonpenetrance. Boeckel et al. (1999) observed nonpenetrance in at least 2 individuals, brothers, both of whom transmitted the disorder to children. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, TYR150TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137854454,
|
|
|
|
|
|
|
|
ClinVar: RCV000018215
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Metcalfe et al. (2000) identified a tyr150-to-ter (Y150X) mutation in exon 9 of the ELN gene in 4 unrelated patients with SVAS (185500) among 100 patients screened. Haplotype analysis using ELN flanking and intragenic markers showed no evidence of a founder effect; therefore this appeared to be a mutation hotspot. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, LYS176TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137854455,
|
|
|
|
|
|
|
|
ClinVar: RCV000018216
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Metcalfe et al. (2000) detected a lys176-to-ter (K176X; 526A-T) mutation in exon 10 of the ELN gene in 2 apparently unrelated familial cases of SVAS (185500) among 100 patients screened. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 SUPRAVALVULAR AORTIC STENOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, ARG610GLN AND 24-BP DUP, NT1034
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2131923188, rs2132323982,
|
|
|
|
|
|
|
|
ClinVar: RCV000018217, RCV001561045, RCV001754635
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 related families with supravalvular aortic stenosis (185500), Urban et al. (2001) identified 2 ELN mutations located on the same allele: an in-frame duplication of nucleotides 1034-1057 in exon 18, and an 1829G-A change in exon 26 predicted to result in an arg610-to-gln (R610Q) substitution. In 1 family, an individual was identified with a recombination between exons 18 and 26 of the ELN gene. This individual was unaffected and carried the exon 18 insertion mutation but not 1829G-A. Skin fibroblasts were established from this recombinant normal individual and from an affected individual carrying both of the mutations. RT-PCR analysis indicated that the expression of the mutant allele was reduced to 12 to 27% of that of the normal allele in the affected but not in the unaffected individual. Further studies showed reduced steady-state elastin mRNA levels and tropoelastin synthesis in the affected individual. RT-PCR analysis of the mRNA rescued by cycloheximide treatment indicated that the 1829G-A mutation created a cryptic donor splice site within exon 26, resulting in the deletion of 4 nucleotides at the 3-prime end of exon 26 and a frameshift in the mRNA. This frameshift mutation generated a premature termination codon in the domain encoded by exon 28, clearly resulting in nonsense-mediated decay of this frameshift RNA product. Despite considerable variability in the molecular nature of mutations responsible for SVAS, the unifying mechanism appears to be the generation of null alleles by nonsense-mediated decay leading to elastin haploinsufficiency. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ELN, EX9-33DUP
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000018218
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mother and daughter with cutis laxa (123700) and severe pulmonary disease, originally described by Beighton (1972) and Corbett et al. (1994), Urban et al. (2005) identified no mutations in the elastin gene by direct sequencing, but detected an abnormal protein in cultured dermal fibroblasts using metabolic labeling and immunoprecipitation. Mutation and gene expression analyses established the presence of a heterozygous complex rearrangement involving the duplication of exons 9 to 33, with a third copy of exons 9 and 10 and intron 10 added to the end of the mRNA; nucleotides 3-65 of intron 10 encode a 21-amino acid missense peptide sequence before ending in a stop codon. Immunoprecipitation experiments revealed that the mutant tropoelastin is partially secreted and partially retained intracellularly; a polyclonal antibody raised against a unique peptide in the mutant molecule showed both intracellular and matrix staining. </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>.0017 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ELN, 25-BP DEL, NT2114
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<br />
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ClinVar: RCV000018219
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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 affected members of a 3-generation family of Japanese and German ancestry with cutis laxa (123700) and aortic aneurysmal disease, Szabo et al. (2006) identified heterozygosity for a 25-bp deletion beginning at nucleotide 2114 in exon 30 of the ELN gene. There was variable expression of cutis laxa, hernias, and aortic lesions in affected family members. The mutation was not found in 121 controls. </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>.0018 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ELN, 1-BP DEL, 2159C
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<br />
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ClinVar: RCV000018220
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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 Singaporean girl of Chinese descent with cutis laxa (123700) and aortic aneurysmal disease, Szabo et al. (2006) identified heterozygosity for a de novo 1-bp deletion (2159delC) in exon 30 of the ELN gene. The mutation was not found in either of her parents or in 121 controls. </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>.0019 CUTIS LAXA, AUTOSOMAL DOMINANT 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ELN, 1621C-T
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<br />
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ClinVar: RCV000018207, RCV000018221, RCV000198624, RCV004532381
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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 boy with severe cutis laxa (123700), severe congenital pulmonary disease (previously not reported in ADCL), and supravalvular pulmonary artery stenosis, Graul-Neumann et al. (2008) identified a heterozygous 1621C-T transition in the ELN gene, resulting in an in-frame deletion of exon 25 and predicting a protein lacking amino acids 527-540. The same mutation was present in the clinically healthy father, but not in the mother, the paternal grandparents, or 96 healthy controls. Analysis of ELN expression in fibroblasts revealed the same amount of complete ELN mRNA in the proband as in normal age-matched controls, whereas the father had a more than 50% reduction of ELN mRNA expression as compared to corresponding age-matched controls. In contrast, addition of the translation inhibitor puromcin caused an increase in total ELN mRNA expression in the father. Graul-Neumann et al. (2008) concluded that the variable processing of an identically mutated gene (dominant negative in the child and haploinsufficiency in the father) caused the highly variable clinical appearance of ADCL in this family. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0020 SUPRAVALVULAR AORTIC STENOSIS</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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ELN, IVS28, G-C, +5
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<br />
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SNP: rs1554686162,
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ClinVar: RCV000022536
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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 3-generation family with supravalvular aortic stenosis (SVAS; 185500), Micale et al. (2010) identified a heterozygous 2044+5G-C transversion in intron 28 of the ELN gene. The mutation was present in all 3 family members who had been diagnosed with SVAS as well as in 1 asymptomatic family member; it was not found in 2 more unaffected family members or in 100 unrelated control samples. RT-PCR analysis of elastin mRNA from transfected HEK293 cells as well as patient fibroblasts demonstrated 2 distinct transcripts, a 200-bp band corresponding to wildtype mRNA product and a 300-bp mutant; sequencing confirmed that the longer transcript resulted from splicing failure and inclusion of intron 28 in the mRNA, predicting a shorter elastin protein with a premature termination codon within the same intron. Assessment of ELN mRNA expression level after incubation of patient fibroblasts with an inhibitor of nonsense-mediated decay (NMD) showed no significant increase in ELN mRNA aberrant transcript, indicating that this mutation is conceivably not a substrate of NMD. </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>See Also:</strong>
|
|
</span>
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|
</h4>
|
|
<span class="mim-text-font">
|
|
Reidy (1963); Sephel et al. (1989)
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|
</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Beighton, P. H.
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<strong>The dominant and recessive forms of cutis laxa.</strong>
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J. Med. Genet. 9: 216-221, 1972.
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[PubMed: 5046633]
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[Full Text: https://doi.org/10.1136/jmg.9.2.216]
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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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Boeckel, T., Dierks, A., Vergopoulos, A., Bahring, S., Knoblauch, H., Muller-Myhsok, B., Baron, H., Aydin, A., Bein, G., Luft, F. C., Schuster, H.
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|
<strong>A new mutation in the elastin gene causing supravalvular aortic stenosis.</strong>
|
|
Am. J. Cardiol. 83: 1141-1143, 1999.
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[PubMed: 10190538]
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[Full Text: https://doi.org/10.1016/s0002-9149(99)00032-6]
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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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Corbett, E., Glaisyer, H., Chan, C., Madden, B., Khaghani, A., Yacoub, M.
|
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<strong>Congenital cutis laxa with a dominant inheritance and early onset emphysema.</strong>
|
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Thorax 49: 836-837, 1994.
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[PubMed: 8091333]
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[Full Text: https://doi.org/10.1136/thx.49.8.836]
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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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Curran, M. E., Atkinson, D. L., Ewart, A. K., Morris, C. A., Leppert, M. F., Keating, M. T.
|
|
<strong>The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis.</strong>
|
|
Cell 73: 159-168, 1993.
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[PubMed: 8096434]
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[Full Text: https://doi.org/10.1016/0092-8674(93)90168-p]
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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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|
Duba, H.-C., Doll, A., Neyer, M., Erdel, M., Mann, C., Hammerer, I., Utermann, G., Grzeschik, K.-H.
|
|
<strong>The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome.</strong>
|
|
Europ. J. Hum. Genet. 10: 351-361, 2002.
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[PubMed: 12080386]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200812]
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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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Emanuel, B. S., Cannizzaro, L., Ornstein-Goldstein, N., Indik, Z. K., Yoon, K., May, M., Oliver, L., Boyd, C., Rosenbloom, J.
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<strong>Chromosomal localization of the human elastin gene.</strong>
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Am. J. Hum. Genet. 37: 873-882, 1985.
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[PubMed: 3840328]
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</p>
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<li>
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<p class="mim-text-font">
|
|
Ewart, A. K., Jin, W., Atkinson, D., Morris, C. A., Keating, M. T.
|
|
<strong>Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.</strong>
|
|
J. Clin. Invest. 93: 1071-1077, 1994.
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|
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[PubMed: 8132745]
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[Full Text: https://doi.org/10.1172/JCI117057]
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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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Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A. D., Leppert, M., Keating, M. T.
|
|
<strong>Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.</strong>
|
|
Nature Genet. 5: 11-16, 1993.
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[PubMed: 7693128]
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[Full Text: https://doi.org/10.1038/ng0993-11]
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</p>
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<li>
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<p class="mim-text-font">
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Ewart, A. K., Morris, C. A., Ensing, G. J., Loker, J., Moore, C., Leppert, M., Keating, M.
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<strong>A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.</strong>
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Proc. Nat. Acad. Sci. 90: 3226-3230, 1993.
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[PubMed: 8475063]
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[Full Text: https://doi.org/10.1073/pnas.90.8.3226]
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<p class="mim-text-font">
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Faury, G., Pezet, M., Knutsen, R. H., Boyle, W. A., Heximer, S. P., McLean, S. E., Minkes, R. K., Blumer, K. J., Kovacs, A., Kelly, D. P., Li, D. Y., Starcher, B., Mecham, R. P.
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<strong>Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency.</strong>
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J. Clin. Invest. 112: 1419-1428, 2003.
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[PubMed: 14597767]
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[Full Text: https://doi.org/10.1172/JCI19028]
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Fazio, M. J., Mattei, M.-G., Passage, E., Chu, M.-L., Black, D., Solomon, E., Davidson, J. M., Uitto, J.
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<strong>Human elastin gene: new evidence for localization to the long arm of chromosome 7.</strong>
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Am. J. Hum. Genet. 48: 696-703, 1991.
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[PubMed: 2014796]
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<p class="mim-text-font">
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Foster, K., Ferrell, R., King-Underwood, L., Povey, S., Attwood, J., Rennick, R., Humphries, S. E., Henney, A. M.
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<strong>Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7.</strong>
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Ann. Hum. Genet. 57: 87-96, 1993.
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[PubMed: 8368807]
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[Full Text: https://doi.org/10.1111/j.1469-1809.1993.tb00890.x]
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<li>
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<p class="mim-text-font">
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Graul-Neumann, L. M., Hausser, I., Essayie, M., Rauch, A., Kraus, C.
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<strong>Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene.</strong>
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Am. J. Med. Genet. 146A: 977-983, 2008.
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[PubMed: 18348261]
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[Full Text: https://doi.org/10.1002/ajmg.a.32242]
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</p>
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<li>
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<p class="mim-text-font">
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Hirano, E., Knutsen, R. H., Sugitani, H., Ciliberto, C. H., Mecham, R. P.
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<strong>Functional rescue of elastin insufficiency in mice by the human elastin gene.</strong>
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</p>
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<li>
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<p class="mim-text-font">
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Indik, Z., Yeh, H., Ornstein-Goldstein, N., Sheppard, P., Anderson, N., Rosenbloom, J. C., Peltonen, L., Rosenbloom, J.
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<strong>Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA.</strong>
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Proc. Nat. Acad. Sci. 84: 5680-5684, 1987.
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[PubMed: 3039501]
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[Full Text: https://doi.org/10.1073/pnas.84.16.5680]
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<li>
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<p class="mim-text-font">
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Indik, Z., Yoon, K., Morrow, S. D., Cicila, G., Rosenbloom, J., Rosenbloom, J., Ornstein-Goldstein, N.
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<strong>Structure of the 3-prime region of the human elastin gene: great abundance of Alu repetitive sequences and few coding sequences.</strong>
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Connect. Tissue Res. 16: 197-211, 1987.
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[PubMed: 3038460]
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[Full Text: https://doi.org/10.3109/03008208709006976]
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<li>
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<p class="mim-text-font">
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Koch, A., Buheitel, G., Hofbeck, M., Rauch, A., Kraus, C., Tassabehji, M., Singer, H.
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<strong>Spectrum of arterial obstructions caused by one elastin gene point mutation.</strong>
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Europ. J. Pediat. 162: 53-54, 2003.
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[PubMed: 12607532]
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<p class="mim-text-font">
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Lee, S.-H., Goswami, S., Grudo, A., Song, L., Bandi, V., Goodnight-White, S., Green, L., Hacken-Bitar, J., Huh, J., Bakaeen, F., Coxson, H. O., Cogswell, S., Storness-Bliss, C., Corry, D. B., Kheradmand, F.
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<strong>Antielastin autoimmunity in tobacco smoking-induced emphysema.</strong>
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Nature Med. 13: 567-569, 2007.
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[PubMed: 17450149]
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[Full Text: https://doi.org/10.1038/nm1583]
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</p>
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<li>
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<p class="mim-text-font">
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Li, D. Y., Brooke, B., Davis, E. C., Mecham, R. P., Sorensen, L. K., Boak, B. B., Eichwald, E., Keating, M. T.
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<strong>Elastin is an essential determinant of arterial morphogenesis.</strong>
|
|
Nature 393: 276-280, 1998.
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|
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[PubMed: 9607766]
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[Full Text: https://doi.org/10.1038/30522]
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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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Li, D. Y., Faury, G., Taylor, D. G., Davis, E. C., Boyle, W. A., Mecham, R. P., Stenzel, P., Boak, B., Keating, M. T.
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|
<strong>Novel arterial pathology in mice and humans hemizygous for elastin.</strong>
|
|
J. Clin. Invest. 102: 1783-1787, 1998.
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|
|
[PubMed: 9819363]
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[Full Text: https://doi.org/10.1172/JCI4487]
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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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Li, D. Y., Toland, A. E., Boak, B. B., Atkinson, D. L., Ensing, G. J., Morris, C. A., Keating, M. T.
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Marla J. F. O'Neill - updated : 3/14/2012<br>Kelly A. Przylepa - updated : 11/20/2008<br>Patricia A. Hartz - updated : 5/1/2008<br>Paul J. Converse - updated : 6/11/2007<br>Marla J. F. O'Neill - updated : 4/19/2006<br>Victor A. McKusick - updated : 5/10/2004<br>Natalie E. Krasikov - updated : 2/19/2004<br>Michael B. Petersen - updated : 2/11/2003<br>Victor A. McKusick - updated : 7/17/2002<br>Victor A. McKusick - updated : 12/6/2001<br>Michael B. Petersen - updated : 4/17/2001<br>Victor A. McKusick - updated : 8/16/2000<br>Victor A. McKusick - updated : 5/14/1999<br>Ada Hamosh - updated : 3/18/1999<br>Victor A. McKusick - updated : 1/5/1999<br>Victor A. McKusick - updated : 12/1/1998<br>Victor A. McKusick - updated : 6/19/1998<br>Victor A. McKusick - updated : 6/15/1998<br>Victor A. McKusick - updated : 10/24/1997<br>Victor A. McKusick - updated : 8/15/1997<br>Moyra Smith - updated : 10/21/1996
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