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<title>
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Entry
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- *102620 - ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA; ACTA2
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- OMIM
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</ul>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<a href="/history"> Search History </a>
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</ul>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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</form>
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<p />
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*102620</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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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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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="#description">Description</a>
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</li>
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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="#geneStructure">Gene Structure</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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/102620">Table View</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>
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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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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000107796;t=ENST00000224784" 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=59" 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=102620" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000107796;t=ENST00000224784" 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_001141945,NM_001320855,NM_001406462,NM_001406463,NM_001406464,NM_001406466,NM_001406467,NM_001406468,NM_001406469,NM_001406471,NM_001613" 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_001613" 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=102620" 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=00031&isoform_id=00031_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/ACTA2" 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/28330,178027,178067,338235,4433118,4501883,17028467,49168522,51316972,56788033,62202492,119570538,119570539,119570540,189053843,194374075,213688375,221043180,270048010,1003701537,2239783909,2239788212,2239789527,2239790798,2239796390,2239796620,2239796658,2239796743" 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/P62736" 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=59" 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=ENSG00000107796;t=ENST00000224784" 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=ACTA2" 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=ACTA2" 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+59" 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/ACTA2" 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:59" 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/59" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr10&hgg_gene=ENST00000224784.10&hgg_start=88935074&hgg_end=88991337&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:130" 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:130" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=102620[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=102620[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/ACTA2/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/ENSG00000107796" 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=ACTA2" 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=ACTA2" 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=ACTA2" 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=ACTA2&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/PA24456" 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:130" 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:87909" 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/ACTA2#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:87909" 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/59/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=59" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-1229" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:59" 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=ACTA2&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> 782724001<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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102620
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA; ACTA2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
ACTIN, ALPHA, SMOOTH MUSCLE, AORTIC; ACTSA<br />
|
|
ACTIN, VASCULAR SMOOTH MUSCLE
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ACTA2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ACTA2</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/10/376?start=-3&limit=10&highlight=376">10q23.31</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:88935074-88991337&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">10:88,935,074-88,991,337</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;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
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Location
|
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</th>
|
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<th>
|
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Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=611788,614042,613834" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
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10q23.31
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Aortic aneurysm, familial thoracic 6
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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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Moyamoya disease 5
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<span class="mim-font">
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<a href="/entry/614042"> 614042 </a>
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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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Smooth muscle dysfunction syndrome
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<a href="/entry/613834"> 613834 </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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<li><a href="/graph/linear/102620" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/102620" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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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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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>Smooth muscle aortic alpha-actin (ACTA2) is 1 of 6 different actin isoforms that have been identified in vertebrates and that share similar amino acid sequences and are well conserved in evolution. Other actins include skeletal muscle (ACTA1; <a href="/entry/102610">102610</a>), cardiac muscle (ACTC1; <a href="/entry/102540">102540</a>) , smooth muscle enteric (ACTG2; <a href="/entry/102545">102545</a>), and cytoplasmic beta (ACTB; <a href="/entry/102630">102630</a>) and gamma (ACTG1; <a href="/entry/102560">102560</a>) (summary by <a href="#17" class="mim-tip-reference" title="Vandekerckhove, J., Weber, K. <strong>The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle.</strong> Differentiation 14: 123-133, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/499690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">499690</a>] [<a href="https://doi.org/10.1111/j.1432-0436.1979.tb01021.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="499690">Vandekerckhove and Weber, 1979</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=499690" 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>Cloning and Expression</strong>
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<p><a href="#15" class="mim-tip-reference" title="Ueyama, H., Hamada, H., Battula, N., Kakunaga, T. <strong>Structure of a human smooth muscle actin gene (aortic type) with a unique intron site.</strong> Molec. Cell. Biol. 4: 1073-1078, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6330528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6330528</a>] [<a href="https://doi.org/10.1128/mcb.4.6.1073-1078.1984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6330528">Ueyama et al. (1984)</a> isolated and characterized the ACTA2 gene, encoding smooth muscle aortic actin. The gene has a transition point mutation in position 309, substituting thymine for cytosine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6330528" 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>Gene Structure</strong>
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<p><a href="#15" class="mim-tip-reference" title="Ueyama, H., Hamada, H., Battula, N., Kakunaga, T. <strong>Structure of a human smooth muscle actin gene (aortic type) with a unique intron site.</strong> Molec. Cell. Biol. 4: 1073-1078, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6330528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6330528</a>] [<a href="https://doi.org/10.1128/mcb.4.6.1073-1078.1984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6330528">Ueyama et al. (1984)</a> found that the ACTA2 gene contains at least 9 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6330528" 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>Mapping</strong>
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<p><a href="#14" class="mim-tip-reference" title="Ueyama, H., Bruns, G., Kanda, N. <strong>Assignment of the vascular smooth muscle actin gene ACTSA to human chromosome 10.</strong> Jinrui Idengaku Zasshi 35: 145-150, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2398629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2398629</a>] [<a href="https://doi.org/10.1007/BF01876459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2398629">Ueyama et al. (1990)</a> assigned the ACTSA gene to chromosome 10 by Southern blot analysis of DNAs from 18 rodent-human somatic cell hybrids. Regional mapping by in situ hybridization localized the gene to chromosome 10q22-q24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2398629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By FISH analysis, <a href="#16" class="mim-tip-reference" title="Ueyama, H., Inazawa, J., Ariyama, T., Nishino, H., Ochiai, Y., Ohkubo, I., Miwa, T. <strong>Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization.</strong> Jpn. J. Hum. Genet. 40: 145-148, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7780165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7780165</a>] [<a href="https://doi.org/10.1007/BF01874078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7780165">Ueyama et al. (1995)</a> localized the ACTA2 gene to chromosome 10q23.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7780165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Kumar, M. S., Hendrix, J. A., Johnson, A. D., Owens, G. K. <strong>Smooth muscle alpha-actin gene requires two E-boxes for proper expression in vivo and is a target of class I basic helix-loop-helix proteins.</strong> Circ. Res. 92: 840-847, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12663487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12663487</a>] [<a href="https://doi.org/10.1161/01.RES.0000069031.55281.7C" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12663487">Kumar et al. (2003)</a> developed transgenic mice expressing a reporter construct driven by the rat Actsa promoter. Mutation of 1 or both E boxes within the promoter significantly reduced expression of the reporter gene. Mouse fibroblasts cotransfected with the reporter plasmid and various transcription factors revealed that serum response factor (SRF; <a href="/entry/600589">600589</a>), class I bHLH proteins, such as E12 (<a href="/entry/147141">147141</a>), HEB (<a href="/entry/600480">600480</a>), and E2-2 (<a href="/entry/602272">602272</a>), and the bHLH inhibitors ID (see ID1; <a href="/entry/600349">600349</a>) and TWIST (<a href="/entry/601622">601622</a>) are likely important regulators of smooth muscle cell differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12663487" 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>Aortic Aneurysm, Familial Thoracic 6</em></strong></p><p>
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The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin, encoded by ACTA2, and the beta-myosin heavy chain, encoded by the MYH11 gene (<a href="/entry/160745">160745</a>). <a href="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a> showed that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (AAT6; <a href="/entry/611788">611788</a>). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrated that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial thoracic aortic aneurysm, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta. Since mutations in 2 components of the SMC contractile unit, ACTA2 and MYH11, cause familial thoracic aortic aneurysm with dissection (TAAD), <a href="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a> raised the possibility that mutations in other components of the SMC contractile unit may be responsible for a portion of the 80% of familial TAAD yet to be explained. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994018" 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="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a> found that the penetrance of TAAD in individuals with ACTA2 mutations was low (0.48) and did not increase with age, differing from the pattern for other identified loci and genes for familial TAAD, which have a higher, age-related penetrance. Despite the young age of death of some family members, the Kaplan-Meier survival curve of the ACTA2 cohort estimated a median survival of 67 years, suggesting that the disease is less deadly than Loeys-Dietz syndrome (<a href="/entry/609192">609192</a>) and similar to treated Marfan syndrome (MFS; <a href="/entry/154700">154700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994018" 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 40 German probands with thoracic aortic aneurysms, 21 of whom had clinical features suggestive of Marfan syndrome, but all of whom were negative for mutation in the FBN1 (<a href="/entry/134797">134797</a>) and TGFBR2 (<a href="/entry/190182">190182</a>) genes, <a href="#5" class="mim-tip-reference" title="Hoffjan, S., Waldmuller, S., Blankenfeldt, W., Kotting, J., Gehle, P., Binner, P., Epplen, J. T., Scheffold, T. <strong>Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.</strong> Europ. J. Hum. Genet. 19: 520-524, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21248741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21248741</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21248741[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.2010.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21248741">Hoffjan et al. (2011)</a> sequenced the ACTA2 gene and identified heterozygous mutations in 3 patients (see, e.g., <a href="#0005">102620.0005</a> and <a href="#0006">102620.0006</a>). None of the 21 individuals with features suggestive of MFS were found to carry a mutation in ACTA2. Among the remaining 19 patients, there were no differences between the 3 patients with ACTA2 mutations and the nonmutated patients. The authors also noted that there was no history of premature stroke or coronary artery disease in the mutation-positive families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21248741" 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>Aortic Aneurysm and/or Moyamoya Disease</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al. (2009)</a> studied 20 families with 127 members harboring heterozygous ACTA2 mutations and phenotyped them for premature vascular disease, defined as an age of onset less than 55 years in men and less than 60 years in women. Family members aged 21 years and older were included, along with members who presented with vascular diseases at younger ages. Thoracic aortic aneurysm had been reported in 14 of these 20 families by <a href="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a>. The 6 additional families with ACTA2 mutations all carried missense mutations. None of these missense mutations was identified in 192 ethnically matched controls. Thoracic aortic aneurysm was the primary vascular disease in ACTA2 mutation carriers (76 individuals); 26 individuals had premature onset of coronary artery disease, and 15 had ischemic strokes. Fifteen individuals had more than 1 vascular disease, and none of the family members without an ACTA2 mutation had any of these early-onset vascular diseases. One family had more mutation carriers with premature coronary artery disease than with aortic disease. In 3 families with an ACTA2 mutation altering the arginine-258 residue (arg258 to cys, <a href="#0003">102620.0003</a>, arg258 to his, <a href="#0002">102620.0002</a>), 10 of 14 mutation carriers had aortic disease and 7 had onset of strokes at ages ranging from 5 to 46 years. Five of the 7 acute strokes had been classified as moyamoya disease (MYMY5; <a href="/entry/614042">614042</a>); 2 others had fusiform cerebral aneurysms. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19409525+17994018" 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="#13" class="mim-tip-reference" title="Shimojima, K., Yamamoto, T. <strong>ACTA2 is not a major disease-causing gene for moyamoya disease. (Letter)</strong> J. Hum. Genet. 54: 687-688, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19745835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19745835</a>] [<a href="https://doi.org/10.1038/jhg.2009.91" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19745835">Shimojima and Yamamoto (2009)</a> analyzed all coding exons of the ACTA2 gene in 53 Japanese patients with moyamoya disease but found no mutations. Noting that the diagnosis of moyamoya disease in the patients studied by <a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al. (2009)</a> was unclear, <a href="#13" class="mim-tip-reference" title="Shimojima, K., Yamamoto, T. <strong>ACTA2 is not a major disease-causing gene for moyamoya disease. (Letter)</strong> J. Hum. Genet. 54: 687-688, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19745835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19745835</a>] [<a href="https://doi.org/10.1038/jhg.2009.91" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19745835">Shimojima and Yamamoto (2009)</a> concluded that ACTA2 is not a major disease-causing gene for moyamoya disease in Japanese patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19409525+19745835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Roder, C., Peters, V., Kasuya, H., Nishizawa, T., Wakita, S., Berg, D., Schulte, C., Khan, N., Tatagiba, M., Krischek, B. <strong>Analysis of ACTA2 in European Moyamoya disease patients.</strong> Europ. J. Paediat. Neurol. 15: 117-122, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20970362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20970362</a>] [<a href="https://doi.org/10.1016/j.ejpn.2010.09.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20970362">Roder et al. (2011)</a> identified a heterozygous mutation in the ACTA2 gene (R179H; <a href="#0004">102620.0004</a>) in 1 of 39 unrelated patients of European descent with moyamoya disease who had no family history of the disorder. No other previously described ACTA2 mutations associated with moyamoya disease (<a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al., 2009</a>) were found in this cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19409525+20970362" 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>Smooth Muscle Dysfunction Syndrome</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S. <strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong> Am. J. Med. Genet. 152A: 2437-2443, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20734336">Milewicz et al. (2010)</a> identified 7 unrelated patients with the same de novo missense mutation in the ACTA2 gene (R179H; <a href="#0004">102620.0004</a>) who presented with a multisystemic smooth muscle dysfunction syndrome (SMDYS; <a href="/entry/613834">613834</a>), including vasculopathy, congenital mydriasis, patent ductus arteriosus, and thoracic aortic aneurysm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20734336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated females with SMDYS, including 1 of the patients (patient E) reported by <a href="#9" class="mim-tip-reference" title="Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S. <strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong> Am. J. Med. Genet. 152A: 2437-2443, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20734336">Milewicz et al. (2010)</a>, <a href="#18" class="mim-tip-reference" title="Yetman, A. T., Starr, L. J., Bleyl, S. B., Meyers, L., Delaney, J. W. <strong>Progressive aortic dilation associated with ACTA2 mutations presenting in infancy.</strong> Pediatrics 136: e262-e266, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26034244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26034244</a>] [<a href="https://doi.org/10.1542/peds.2014-3032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26034244">Yetman et al. (2015)</a> identified heterozygosity for the R179H mutation in the ACTA2 gene. All 3 presented with an aneurysmal patent ductus arteriosus, leading the authors to suggest that all infants with ductal aneurysms be tested for ACTA2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20734336+26034244" 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>From a cohort of 7 patients with visceral myopathy phenotypes, <a href="#10" class="mim-tip-reference" title="Moreno, C. A., Metze, K., Lomazi, E. A., Bertola, D. R., Barbosa, R. H. A., Cosentino, V., Sobreira, N., Cavalcanti, D. P. <strong>Visceral myopathy: clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.</strong> Am. J. Med. Genet. 170A: 2965-2974, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27481187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27481187</a>] [<a href="https://doi.org/10.1002/ajmg.a.37857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27481187">Moreno et al. (2016)</a> identified a 2.75-year-old Brazilian girl (patient 7) with SMYDS who was heterozygous for an R179C mutation in the ACTA2 gene (<a href="#0008">102620.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27481187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others. <strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong> Genet. Med. 20: 1206-1215, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29300374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29300374</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29300374[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/gim.2017.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29300374">Regalado et al. (2018)</a> reviewed 33 patients with SMDYS, including the patients reported by <a href="#9" class="mim-tip-reference" title="Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S. <strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong> Am. J. Med. Genet. 152A: 2437-2443, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20734336">Milewicz et al. (2010)</a>, all of whom had an alteration at the R179 position of ACTA2 (see <a href="#0004">102620.0004</a>; <a href="#0007">102620.0007</a>-<a href="#0009">102620.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20734336+29300374" 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> rs121434526 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434526;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/rs121434526?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=rs121434526" 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=rs121434526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a large family in which thoracic aortic aneurysm with dissection segregated with reduced penetrance (AAT6; <a href="/entry/611788">611788</a>), <a href="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a> found a heterozygous 492C-T transition in exon 5 of the ACTA2 gene that caused an arg149-to-cys (R149C) amino acid substitution. In further studies, 4 additional families with the ACTA2 mutation were found; however, each family had a unique haplotype, implying that the mutations arose de novo in multiple families. Livedo reticularis and iris flocculi were found together or separately in some of these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al. (2009)</a> analyzed 45 individuals with the R149C mutation and found that, in addition to the already established predisposition to TAAD, this mutation led to coronary artery disease (24 mutation carriers with TAAD, 12 with coronary artery disease). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19409525" 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">rs121434527 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434527;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=rs121434527" 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=rs121434527" 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=RCV000019939 OR RCV000022435 OR RCV000181027 OR RCV003352750" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019939, RCV000022435, RCV000181027, RCV003352750" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019939...</a>
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<p>In a family of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; <a href="/entry/611788">611788</a>), <a href="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a> identified an 820G-A transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-his (R258H) substitution. One individual in the family had patent ductus arteriosus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al. (2009)</a> analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). In 1 family with the R258H mutation, 3 affected individuals had a phenotype consistent with moyamoya disease-5 (MYMY5; <a href="/entry/614042">614042</a>). Two of these 3 patients had strokes at ages 44 and 46 years, respectively, and also had thoracic aortic aneurysm with dissection; the third had isolated moyamoya disease with stroke at age 16 years. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19409525" 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> rs121434528 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434528;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/rs121434528?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=rs121434528" 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=rs121434528" 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=RCV000019940 OR RCV000022436 OR RCV000523600 OR RCV002310630" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019940, RCV000022436, RCV000523600, RCV002310630" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019940...</a>
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<p>In 2 families of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; <a href="/entry/611788">611788</a>), <a href="#3" class="mim-tip-reference" title="Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong> Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>] [<a href="https://doi.org/10.1038/ng.2007.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994018">Guo et al. (2007)</a> identified an 819C-T transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-cys (R258C) substitution. All 5 mutation carriers in 1 family had patent ductus arteriosus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al. (2009)</a> analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). The authors identified a high risk of early-onset strokes in family members carrying the R258C mutation. In 1 family with the R258C mutation, 2 members had a phenotype consistent with moyamoya disease-5 (<a href="/entry/614042">614042</a>), with strokes at ages 39 and 5 years, respectively. The older patient had thoracic aneurysm with dissection at age 32 years, whereas the stroke was fatal in the younger patient. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19409525" 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">rs387906592 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906592;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=rs387906592" 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=rs387906592" 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=RCV000022437 OR RCV000022438 OR RCV000181023 OR RCV000211886 OR RCV000228180 OR RCV000415107 OR RCV000763224 OR RCV004532396" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022437, RCV000022438, RCV000181023, RCV000211886, RCV000228180, RCV000415107, RCV000763224, RCV004532396" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022437...</a>
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<p><strong><em>Smooth Muscle Dysfunction Syndrome</em></strong></p><p>
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In 7 unrelated patients of northern European descent with smooth muscle dysfunction syndrome (SMDYS; <a href="/entry/613834">613834</a>), <a href="#9" class="mim-tip-reference" title="Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S. <strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong> Am. J. Med. Genet. 152A: 2437-2443, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20734336">Milewicz et al. (2010)</a> identified heterozygosity for a de novo arg179-to-his (R179H) substitution in the ACTA2 gene. The mutation was not identified in parents' DNA samples, confirming the de novo status in 5 patients. Three of the patients had previously been reported (<a href="#1" class="mim-tip-reference" title="Ades, L. C., Davies, R., Haan, E. A., Holman, K. J., Watson, K. C., Sreetharan, D., Cao, S. N., Milewicz, D. M., Bateman, J. F., Chiodo, A. A., Eccles, M., McNoe, L., Harbord, M. <strong>Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.</strong> Clin. Dysmorph. 8: 269-276, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10532176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10532176</a>]" pmid="10532176">Ades et al., 1999</a>, <a href="#6" class="mim-tip-reference" title="Khan, N., Schinzel, A., Shuknecht, B., Baumann, F., Ostergaard, J. R., Yonekawa, Y. <strong>Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus arteriosus and pupillary dysfunction: a new genetic syndrome?</strong> Europ. Neurol. 51: 72-77, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14730227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14730227</a>] [<a href="https://doi.org/10.1159/000076248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14730227">Khan et al., 2004</a>, and <a href="#8" class="mim-tip-reference" title="Lemire, B. D., Buncic, J. R., Kennedy, S. J., Dyack, S. J., Teebi, A. S. <strong>Congenital mydriasis, patent ductus arteriosus, and congenital cystic lung disease: new syndromic spectrum?</strong> Am. J. Med. Genet. 131A: 318-319, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15472996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15472996</a>] [<a href="https://doi.org/10.1002/ajmg.a.30341" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15472996">Lemire et al., 2004</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20734336+15472996+14730227+10532176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Brodsky, M. C., Turan, K. E., Khanna, C. L., Patton, A., Kirmani, S. <strong>Congenital mydriasis and prune belly syndrome in a child with an ACTA2 mutation.</strong> J. AAPOS 18: 393-395, 2014. Note: Erratum: J. AAPOS 18: 518 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24998021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24998021</a>] [<a href="https://doi.org/10.1016/j.jaapos.2014.02.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24998021">Brodsky et al. (2014)</a> identified the R179H mutation in a 9-year-old boy diagnosed with congenital mydriasis and prune belly syndrome with megacystis, bilateral hydroureter, and hydronephrosis requiring surgical correction. On echocardiography at age 9 years, he had severe dilatation of the aortic root and mid-ascending aorta. MRI showed massive dilatation of the intracranial arteries and tortuosity of the distal cerebral vasculature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24998021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated females with SMDYS, including 1 of the patients (patient E) reported by <a href="#9" class="mim-tip-reference" title="Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S. <strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong> Am. J. Med. Genet. 152A: 2437-2443, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20734336">Milewicz et al. (2010)</a>, <a href="#18" class="mim-tip-reference" title="Yetman, A. T., Starr, L. J., Bleyl, S. B., Meyers, L., Delaney, J. W. <strong>Progressive aortic dilation associated with ACTA2 mutations presenting in infancy.</strong> Pediatrics 136: e262-e266, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26034244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26034244</a>] [<a href="https://doi.org/10.1542/peds.2014-3032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26034244">Yetman et al. (2015)</a> identified heterozygosity for the R179H mutation in the ACTA2 gene. All 3 presented with an aneurysmal patent ductus arteriosus, leading the authors to suggest that all infants with ductal aneurysms be tested for ACTA2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20734336+26034244" 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 review of the clinical history and outcomes of 33 patients with SMDYS, <a href="#11" class="mim-tip-reference" title="Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others. <strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong> Genet. Med. 20: 1206-1215, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29300374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29300374</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29300374[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/gim.2017.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29300374">Regalado et al. (2018)</a> found that 24 of the patients were heterozygous for the R179H mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29300374" 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>Moyamoya Disease 5</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Roder, C., Peters, V., Kasuya, H., Nishizawa, T., Wakita, S., Berg, D., Schulte, C., Khan, N., Tatagiba, M., Krischek, B. <strong>Analysis of ACTA2 in European Moyamoya disease patients.</strong> Europ. J. Paediat. Neurol. 15: 117-122, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20970362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20970362</a>] [<a href="https://doi.org/10.1016/j.ejpn.2010.09.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20970362">Roder et al. (2011)</a> identified a heterozygous R179H mutation in 1 of 39 patients of European origin with moyamoya disease-5 (MYMY5; <a href="/entry/614042">614042</a>) and no family history of the disorder. The patient was a girl who had a stroke at age 3 years, but she had no other abnormalities, particularly none of those described by <a href="#9" class="mim-tip-reference" title="Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S. <strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong> Am. J. Med. Genet. 152A: 2437-2443, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20734336">Milewicz et al. (2010)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20734336+20970362" 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> rs112901682 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs112901682;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/rs112901682?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=rs112901682" 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=rs112901682" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 3-generation German family with autosomal dominant thoracic aortic aneurysm (AAT6; <a href="/entry/611788">611788</a>), <a href="#5" class="mim-tip-reference" title="Hoffjan, S., Waldmuller, S., Blankenfeldt, W., Kotting, J., Gehle, P., Binner, P., Epplen, J. T., Scheffold, T. <strong>Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.</strong> Europ. J. Hum. Genet. 19: 520-524, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21248741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21248741</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21248741[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.2010.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21248741">Hoffjan et al. (2011)</a> identified heterozygosity for a c.115C-T transition in exon 2 of the ACTA2 gene, resulting in an arg39-to-cys (R39C) substitution at a highly conserved residue adjacent to the DNAse-I-binding loop within subdomain 2. The mutation segregated with disease in the family and was not found in 192 control chromosomes or in the GenBank dbSNP library. The vascular phenotype was variable in this family, ranging from mild aortic dilation and insufficiency in a 44-year-old woman to overt aortic aneurysm extending from the ascending to the abdominal aorta in a 25-year-old man. None of the affected individuals showed syndromic features, and there was no history of premature stroke or coronary artery disease. <a href="#5" class="mim-tip-reference" title="Hoffjan, S., Waldmuller, S., Blankenfeldt, W., Kotting, J., Gehle, P., Binner, P., Epplen, J. T., Scheffold, T. <strong>Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.</strong> Europ. J. Hum. Genet. 19: 520-524, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21248741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21248741</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21248741[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.2010.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21248741">Hoffjan et al. (2011)</a> noted that although a different mutation at the R39 residue, R39H, had been associated with type A dissections in 2 families and with type B dissections in another family (<a href="#4" class="mim-tip-reference" title="Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. <strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong> Am. J. Hum. Genet. 84: 617-627, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19409525">Guo et al., 2009</a>), dissections were not observed in the family with the R39C mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19409525+21248741" 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 German woman who presented with acute aortic dissection at 37 years of age, <a href="#5" class="mim-tip-reference" title="Hoffjan, S., Waldmuller, S., Blankenfeldt, W., Kotting, J., Gehle, P., Binner, P., Epplen, J. T., Scheffold, T. <strong>Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.</strong> Europ. J. Hum. Genet. 19: 520-524, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21248741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21248741</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21248741[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.2010.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21248741">Hoffjan et al. (2011)</a> identified heterozygosity for a c.145A-G transition in exon 3 of the ACTA2 gene, resulting in a met49-to-val (M49V) substitution at a highly conserved residue in the DNAse-I-binding loop within subdomain 2. The mutation was not found in 192 control chromosomes or in the GenBank dbSNP library. The patient's brother had died at 29 years of age from acute aortic dissection, and her mother, who suffered from slowly progressive spastic paraplegia over 20 years and cancer, died suddenly at 69 years of age in association with a massive drop in blood pressure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21248741" 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>.0007 SMOOTH MUSCLE DYSFUNCTION SYNDROME</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">rs387906592 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906592;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=rs387906592" 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=rs387906592" 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=RCV001267897" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001267897" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001267897</a>
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<p>In a review of the clinical history and outcomes of 33 patients with smooth muscle dysfunction syndrome (SMDYS; <a href="/entry/613834">613834</a>), <a href="#11" class="mim-tip-reference" title="Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others. <strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong> Genet. Med. 20: 1206-1215, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29300374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29300374</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29300374[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/gim.2017.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29300374">Regalado et al. (2018)</a> found 1 patient who was heterozygous for an arg179-to-leu (R179L) substitution in ACTA2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29300374" 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 SMOOTH MUSCLE DYSFUNCTION SYNDROME</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">rs886039303 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039303;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=rs886039303" 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=rs886039303" 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=RCV000255555 OR RCV000700774 OR RCV000780814 OR RCV001265589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000255555, RCV000700774, RCV000780814, RCV001265589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000255555...</a>
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<p>In a 2.75-year-old Brazilian girl (patient 7) with smooth muscle dysfunction syndrome (SMDYS; <a href="/entry/613834">613834</a>), <a href="#10" class="mim-tip-reference" title="Moreno, C. A., Metze, K., Lomazi, E. A., Bertola, D. R., Barbosa, R. H. A., Cosentino, V., Sobreira, N., Cavalcanti, D. P. <strong>Visceral myopathy: clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.</strong> Am. J. Med. Genet. 170A: 2965-2974, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27481187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27481187</a>] [<a href="https://doi.org/10.1002/ajmg.a.37857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27481187">Moreno et al. (2016)</a> identified heterozygosity for a c.535C-T transition in the ACTA2 gene, resulting in an arg179-to-cys (R179C). The mutation was not found in her unaffected mother; DNA was unavailable from the father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27481187" 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 review of the clinical history and outcomes of 33 patients with SMDYS, <a href="#11" class="mim-tip-reference" title="Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others. <strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong> Genet. Med. 20: 1206-1215, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29300374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29300374</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29300374[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/gim.2017.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29300374">Regalado et al. (2018)</a> found 7 patients who were heterozygous for the R179C substitution in ACTA2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29300374" 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 SMOOTH MUSCLE DYSFUNCTION SYNDROME</strong>
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ACTA2, ARG179SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886039303 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039303;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=rs886039303" 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=rs886039303" 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=RCV001164780" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001164780" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001164780</a>
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<p>In a review of the clinical history and outcomes of 33 patients with smooth muscle dysfunction syndrome (SMDYS; <a href="/entry/613834">613834</a>), <a href="#11" class="mim-tip-reference" title="Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others. <strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong> Genet. Med. 20: 1206-1215, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29300374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29300374</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29300374[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/gim.2017.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29300374">Regalado et al. (2018)</a> found 1 patient who was heterozygous for an arg179-to-ser (R179S) substitution in ACTA2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29300374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Ades1999" class="mim-anchor"></a>
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Ades, L. C., Davies, R., Haan, E. A., Holman, K. J., Watson, K. C., Sreetharan, D., Cao, S. N., Milewicz, D. M., Bateman, J. F., Chiodo, A. A., Eccles, M., McNoe, L., Harbord, M.
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<strong>Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.</strong>
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Clin. Dysmorph. 8: 269-276, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10532176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10532176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10532176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Brodsky, M. C., Turan, K. E., Khanna, C. L., Patton, A., Kirmani, S.
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<strong>Congenital mydriasis and prune belly syndrome in a child with an ACTA2 mutation.</strong>
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J. AAPOS 18: 393-395, 2014. Note: Erratum: J. AAPOS 18: 518 only, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24998021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24998021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24998021" 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/10.1016/j.jaapos.2014.02.010" target="_blank">Full Text</a>]
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Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others.
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<strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong>
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Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.2007.6" target="_blank">Full Text</a>]
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Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others.
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<strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong>
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Am. J. Hum. Genet. 84: 617-627, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19409525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19409525[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=19409525" 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/10.1016/j.ajhg.2009.04.007" target="_blank">Full Text</a>]
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Hoffjan, S., Waldmuller, S., Blankenfeldt, W., Kotting, J., Gehle, P., Binner, P., Epplen, J. T., Scheffold, T.
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<strong>Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.</strong>
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Europ. J. Hum. Genet. 19: 520-524, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21248741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21248741</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21248741[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=21248741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2010.239" target="_blank">Full Text</a>]
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<a id="Khan2004" class="mim-anchor"></a>
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Khan, N., Schinzel, A., Shuknecht, B., Baumann, F., Ostergaard, J. R., Yonekawa, Y.
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<strong>Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus arteriosus and pupillary dysfunction: a new genetic syndrome?</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14730227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14730227</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14730227" 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/10.1159/000076248" target="_blank">Full Text</a>]
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Kumar, M. S., Hendrix, J. A., Johnson, A. D., Owens, G. K.
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<strong>Smooth muscle alpha-actin gene requires two E-boxes for proper expression in vivo and is a target of class I basic helix-loop-helix proteins.</strong>
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Circ. Res. 92: 840-847, 2003.
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[<a href="https://doi.org/10.1161/01.RES.0000069031.55281.7C" target="_blank">Full Text</a>]
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<a id="Lemire2004" class="mim-anchor"></a>
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Lemire, B. D., Buncic, J. R., Kennedy, S. J., Dyack, S. J., Teebi, A. S.
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<strong>Congenital mydriasis, patent ductus arteriosus, and congenital cystic lung disease: new syndromic spectrum?</strong>
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[<a href="https://doi.org/10.1002/ajmg.a.30341" target="_blank">Full Text</a>]
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<a id="Milewicz2010" class="mim-anchor"></a>
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<div class="">
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Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S.
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<strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20734336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20734336</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20734336[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=20734336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33657" target="_blank">Full Text</a>]
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<a id="Moreno2016" class="mim-anchor"></a>
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Moreno, C. A., Metze, K., Lomazi, E. A., Bertola, D. R., Barbosa, R. H. A., Cosentino, V., Sobreira, N., Cavalcanti, D. P.
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<strong>Visceral myopathy: clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.</strong>
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Am. J. Med. Genet. 170A: 2965-2974, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27481187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27481187</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27481187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37857" target="_blank">Full Text</a>]
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<a id="Regalado2018" class="mim-anchor"></a>
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Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others.
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<strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong>
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Genet. Med. 20: 1206-1215, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29300374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29300374</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29300374[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=29300374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/gim.2017.245" target="_blank">Full Text</a>]
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Roder, C., Peters, V., Kasuya, H., Nishizawa, T., Wakita, S., Berg, D., Schulte, C., Khan, N., Tatagiba, M., Krischek, B.
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<strong>Analysis of ACTA2 in European Moyamoya disease patients.</strong>
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Europ. J. Paediat. Neurol. 15: 117-122, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20970362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20970362</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20970362" 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/10.1016/j.ejpn.2010.09.002" target="_blank">Full Text</a>]
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Shimojima, K., Yamamoto, T.
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<strong>ACTA2 is not a major disease-causing gene for moyamoya disease. (Letter)</strong>
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J. Hum. Genet. 54: 687-688, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19745835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19745835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19745835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/jhg.2009.91" target="_blank">Full Text</a>]
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<a id="Ueyama1990" class="mim-anchor"></a>
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<div class="">
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Ueyama, H., Bruns, G., Kanda, N.
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<strong>Assignment of the vascular smooth muscle actin gene ACTSA to human chromosome 10.</strong>
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Jinrui Idengaku Zasshi 35: 145-150, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2398629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2398629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2398629" 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/BF01876459" target="_blank">Full Text</a>]
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Ueyama, H., Hamada, H., Battula, N., Kakunaga, T.
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<strong>Structure of a human smooth muscle actin gene (aortic type) with a unique intron site.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6330528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6330528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6330528" 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/10.1128/mcb.4.6.1073-1078.1984" target="_blank">Full Text</a>]
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Ueyama, H., Inazawa, J., Ariyama, T., Nishino, H., Ochiai, Y., Ohkubo, I., Miwa, T.
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<strong>Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization.</strong>
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Jpn. J. Hum. Genet. 40: 145-148, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7780165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7780165</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7780165" 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/BF01874078" target="_blank">Full Text</a>]
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Vandekerckhove, J., Weber, K.
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<strong>The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle.</strong>
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Differentiation 14: 123-133, 1979.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/499690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">499690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=499690" 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.1432-0436.1979.tb01021.x" target="_blank">Full Text</a>]
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Yetman, A. T., Starr, L. J., Bleyl, S. B., Meyers, L., Delaney, J. W.
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<strong>Progressive aortic dilation associated with ACTA2 mutations presenting in infancy.</strong>
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Pediatrics 136: e262-e266, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26034244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26034244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26034244" 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/10.1542/peds.2014-3032" target="_blank">Full Text</a>]
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Sonja A. Rasmussen - updated : 01/19/2023
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Marla J. F. O'Neill - updated : 07/14/2021<br>Ada Hamosh - updated : 05/27/2020<br>Ada Hamosh - updated : 01/15/2020<br>Marla J. F. O'Neill - updated : 09/24/2013<br>Cassandra L. Kniffin - updated : 6/14/2011<br>Ada Hamosh - updated : 3/24/2011<br>Ada Hamosh - updated : 10/6/2009<br>Victor A. McKusick - updated : 12/20/2007<br>Patricia A. Hartz - updated : 3/24/2004
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Victor A. McKusick : 6/4/1986
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<h3>
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<span class="mim-font">
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<strong>*</strong> 102620
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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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ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA; ACTA2
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</span>
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</h3>
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</div>
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<br />
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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ACTIN, ALPHA, SMOOTH MUSCLE, AORTIC; ACTSA<br />
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ACTIN, VASCULAR SMOOTH MUSCLE
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</span>
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</h4>
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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: ACTA2</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> 782724001;
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</span>
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</p>
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 10q23.31
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:88,935,074-88,991,337 </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="3">
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<span class="mim-font">
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10q23.31
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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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Aortic aneurysm, familial thoracic 6
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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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611788
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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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Moyamoya disease 5
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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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614042
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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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</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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Smooth muscle dysfunction syndrome
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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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613834
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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>Description</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>Smooth muscle aortic alpha-actin (ACTA2) is 1 of 6 different actin isoforms that have been identified in vertebrates and that share similar amino acid sequences and are well conserved in evolution. Other actins include skeletal muscle (ACTA1; 102610), cardiac muscle (ACTC1; 102540) , smooth muscle enteric (ACTG2; 102545), and cytoplasmic beta (ACTB; 102630) and gamma (ACTG1; 102560) (summary by Vandekerckhove and Weber, 1979). </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>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>Ueyama et al. (1984) isolated and characterized the ACTA2 gene, encoding smooth muscle aortic actin. The gene has a transition point mutation in position 309, substituting thymine for cytosine. </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>Ueyama et al. (1984) found that the ACTA2 gene contains at least 9 exons. </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>Ueyama et al. (1990) assigned the ACTSA gene to chromosome 10 by Southern blot analysis of DNAs from 18 rodent-human somatic cell hybrids. Regional mapping by in situ hybridization localized the gene to chromosome 10q22-q24. </p><p>By FISH analysis, Ueyama et al. (1995) localized the ACTA2 gene to chromosome 10q23.3. </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>Kumar et al. (2003) developed transgenic mice expressing a reporter construct driven by the rat Actsa promoter. Mutation of 1 or both E boxes within the promoter significantly reduced expression of the reporter gene. Mouse fibroblasts cotransfected with the reporter plasmid and various transcription factors revealed that serum response factor (SRF; 600589), class I bHLH proteins, such as E12 (147141), HEB (600480), and E2-2 (602272), and the bHLH inhibitors ID (see ID1; 600349) and TWIST (601622) are likely important regulators of smooth muscle cell differentiation. </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>Aortic Aneurysm, Familial Thoracic 6</em></strong></p><p>
|
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The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin, encoded by ACTA2, and the beta-myosin heavy chain, encoded by the MYH11 gene (160745). Guo et al. (2007) showed that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (AAT6; 611788). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrated that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial thoracic aortic aneurysm, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta. Since mutations in 2 components of the SMC contractile unit, ACTA2 and MYH11, cause familial thoracic aortic aneurysm with dissection (TAAD), Guo et al. (2007) raised the possibility that mutations in other components of the SMC contractile unit may be responsible for a portion of the 80% of familial TAAD yet to be explained. </p><p>Guo et al. (2007) found that the penetrance of TAAD in individuals with ACTA2 mutations was low (0.48) and did not increase with age, differing from the pattern for other identified loci and genes for familial TAAD, which have a higher, age-related penetrance. Despite the young age of death of some family members, the Kaplan-Meier survival curve of the ACTA2 cohort estimated a median survival of 67 years, suggesting that the disease is less deadly than Loeys-Dietz syndrome (609192) and similar to treated Marfan syndrome (MFS; 154700). </p><p>In 40 German probands with thoracic aortic aneurysms, 21 of whom had clinical features suggestive of Marfan syndrome, but all of whom were negative for mutation in the FBN1 (134797) and TGFBR2 (190182) genes, Hoffjan et al. (2011) sequenced the ACTA2 gene and identified heterozygous mutations in 3 patients (see, e.g., 102620.0005 and 102620.0006). None of the 21 individuals with features suggestive of MFS were found to carry a mutation in ACTA2. Among the remaining 19 patients, there were no differences between the 3 patients with ACTA2 mutations and the nonmutated patients. The authors also noted that there was no history of premature stroke or coronary artery disease in the mutation-positive families. </p><p><strong><em>Aortic Aneurysm and/or Moyamoya Disease</em></strong></p><p>
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Guo et al. (2009) studied 20 families with 127 members harboring heterozygous ACTA2 mutations and phenotyped them for premature vascular disease, defined as an age of onset less than 55 years in men and less than 60 years in women. Family members aged 21 years and older were included, along with members who presented with vascular diseases at younger ages. Thoracic aortic aneurysm had been reported in 14 of these 20 families by Guo et al. (2007). The 6 additional families with ACTA2 mutations all carried missense mutations. None of these missense mutations was identified in 192 ethnically matched controls. Thoracic aortic aneurysm was the primary vascular disease in ACTA2 mutation carriers (76 individuals); 26 individuals had premature onset of coronary artery disease, and 15 had ischemic strokes. Fifteen individuals had more than 1 vascular disease, and none of the family members without an ACTA2 mutation had any of these early-onset vascular diseases. One family had more mutation carriers with premature coronary artery disease than with aortic disease. In 3 families with an ACTA2 mutation altering the arginine-258 residue (arg258 to cys, 102620.0003, arg258 to his, 102620.0002), 10 of 14 mutation carriers had aortic disease and 7 had onset of strokes at ages ranging from 5 to 46 years. Five of the 7 acute strokes had been classified as moyamoya disease (MYMY5; 614042); 2 others had fusiform cerebral aneurysms. </p><p>Shimojima and Yamamoto (2009) analyzed all coding exons of the ACTA2 gene in 53 Japanese patients with moyamoya disease but found no mutations. Noting that the diagnosis of moyamoya disease in the patients studied by Guo et al. (2009) was unclear, Shimojima and Yamamoto (2009) concluded that ACTA2 is not a major disease-causing gene for moyamoya disease in Japanese patients. </p><p>Roder et al. (2011) identified a heterozygous mutation in the ACTA2 gene (R179H; 102620.0004) in 1 of 39 unrelated patients of European descent with moyamoya disease who had no family history of the disorder. No other previously described ACTA2 mutations associated with moyamoya disease (Guo et al., 2009) were found in this cohort. </p><p><strong><em>Smooth Muscle Dysfunction Syndrome</em></strong></p><p>
|
|
Milewicz et al. (2010) identified 7 unrelated patients with the same de novo missense mutation in the ACTA2 gene (R179H; 102620.0004) who presented with a multisystemic smooth muscle dysfunction syndrome (SMDYS; 613834), including vasculopathy, congenital mydriasis, patent ductus arteriosus, and thoracic aortic aneurysm. </p><p>In 3 unrelated females with SMDYS, including 1 of the patients (patient E) reported by Milewicz et al. (2010), Yetman et al. (2015) identified heterozygosity for the R179H mutation in the ACTA2 gene. All 3 presented with an aneurysmal patent ductus arteriosus, leading the authors to suggest that all infants with ductal aneurysms be tested for ACTA2 mutations. </p><p>From a cohort of 7 patients with visceral myopathy phenotypes, Moreno et al. (2016) identified a 2.75-year-old Brazilian girl (patient 7) with SMYDS who was heterozygous for an R179C mutation in the ACTA2 gene (102620.0008). </p><p>Regalado et al. (2018) reviewed 33 patients with SMDYS, including the patients reported by Milewicz et al. (2010), all of whom had an alteration at the R179 position of ACTA2 (see 102620.0004; 102620.0007-102620.0009). </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>9 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 AORTIC ANEURYSM, FAMILIAL THORACIC 6</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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ACTA2, ARG149CYS
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<br />
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SNP: rs121434526,
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gnomAD: rs121434526,
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ClinVar: RCV000019938, RCV000246692, RCV000505736, RCV000581791
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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 large family in which thoracic aortic aneurysm with dissection segregated with reduced penetrance (AAT6; 611788), Guo et al. (2007) found a heterozygous 492C-T transition in exon 5 of the ACTA2 gene that caused an arg149-to-cys (R149C) amino acid substitution. In further studies, 4 additional families with the ACTA2 mutation were found; however, each family had a unique haplotype, implying that the mutations arose de novo in multiple families. Livedo reticularis and iris flocculi were found together or separately in some of these families. </p><p>Guo et al. (2009) analyzed 45 individuals with the R149C mutation and found that, in addition to the already established predisposition to TAAD, this mutation led to coronary artery disease (24 mutation carriers with TAAD, 12 with coronary artery disease). </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 AORTIC ANEURYSM, FAMILIAL THORACIC 6</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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MOYAMOYA DISEASE 5, INCLUDED
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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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ACTA2, ARG258HIS
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<br />
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SNP: rs121434527,
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ClinVar: RCV000019939, RCV000022435, RCV000181027, RCV003352750
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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 family of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; 611788), Guo et al. (2007) identified an 820G-A transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-his (R258H) substitution. One individual in the family had patent ductus arteriosus. </p><p>Guo et al. (2009) analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). In 1 family with the R258H mutation, 3 affected individuals had a phenotype consistent with moyamoya disease-5 (MYMY5; 614042). Two of these 3 patients had strokes at ages 44 and 46 years, respectively, and also had thoracic aortic aneurysm with dissection; the third had isolated moyamoya disease with stroke at age 16 years. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 AORTIC ANEURYSM, FAMILIAL THORACIC 6</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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MOYAMOYA DISEASE 5, INCLUDED
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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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ACTA2, ARG258CYS
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<br />
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SNP: rs121434528,
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gnomAD: rs121434528,
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ClinVar: RCV000019940, RCV000022436, RCV000523600, RCV002310630
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 families of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; 611788), Guo et al. (2007) identified an 819C-T transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-cys (R258C) substitution. All 5 mutation carriers in 1 family had patent ductus arteriosus. </p><p>Guo et al. (2009) analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). The authors identified a high risk of early-onset strokes in family members carrying the R258C mutation. In 1 family with the R258C mutation, 2 members had a phenotype consistent with moyamoya disease-5 (614042), with strokes at ages 39 and 5 years, respectively. The older patient had thoracic aneurysm with dissection at age 32 years, whereas the stroke was fatal in the younger patient. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 SMOOTH MUSCLE DYSFUNCTION SYNDROME</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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MOYAMOYA DISEASE 5, INCLUDED
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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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ACTA2, ARG179HIS
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<br />
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SNP: rs387906592,
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ClinVar: RCV000022437, RCV000022438, RCV000181023, RCV000211886, RCV000228180, RCV000415107, RCV000763224, RCV004532396
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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 />
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<p><strong><em>Smooth Muscle Dysfunction Syndrome</em></strong></p><p>
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In 7 unrelated patients of northern European descent with smooth muscle dysfunction syndrome (SMDYS; 613834), Milewicz et al. (2010) identified heterozygosity for a de novo arg179-to-his (R179H) substitution in the ACTA2 gene. The mutation was not identified in parents' DNA samples, confirming the de novo status in 5 patients. Three of the patients had previously been reported (Ades et al., 1999, Khan et al., 2004, and Lemire et al., 2004, respectively). </p><p>Brodsky et al. (2014) identified the R179H mutation in a 9-year-old boy diagnosed with congenital mydriasis and prune belly syndrome with megacystis, bilateral hydroureter, and hydronephrosis requiring surgical correction. On echocardiography at age 9 years, he had severe dilatation of the aortic root and mid-ascending aorta. MRI showed massive dilatation of the intracranial arteries and tortuosity of the distal cerebral vasculature. </p><p>In 3 unrelated females with SMDYS, including 1 of the patients (patient E) reported by Milewicz et al. (2010), Yetman et al. (2015) identified heterozygosity for the R179H mutation in the ACTA2 gene. All 3 presented with an aneurysmal patent ductus arteriosus, leading the authors to suggest that all infants with ductal aneurysms be tested for ACTA2 mutations. </p><p>In a review of the clinical history and outcomes of 33 patients with SMDYS, Regalado et al. (2018) found that 24 of the patients were heterozygous for the R179H mutation. </p><p><strong><em>Moyamoya Disease 5</em></strong></p><p>
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Roder et al. (2011) identified a heterozygous R179H mutation in 1 of 39 patients of European origin with moyamoya disease-5 (MYMY5; 614042) and no family history of the disorder. The patient was a girl who had a stroke at age 3 years, but she had no other abnormalities, particularly none of those described by Milewicz et al. (2010). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 AORTIC ANEURYSM, FAMILIAL THORACIC 6</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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ACTA2, ARG39CYS
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<br />
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SNP: rs112901682,
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gnomAD: rs112901682,
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ClinVar: RCV000055647, RCV000143866, RCV000490091, RCV002274892, RCV004700355, RCV004734613, RCV004795340
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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 German family with autosomal dominant thoracic aortic aneurysm (AAT6; 611788), Hoffjan et al. (2011) identified heterozygosity for a c.115C-T transition in exon 2 of the ACTA2 gene, resulting in an arg39-to-cys (R39C) substitution at a highly conserved residue adjacent to the DNAse-I-binding loop within subdomain 2. The mutation segregated with disease in the family and was not found in 192 control chromosomes or in the GenBank dbSNP library. The vascular phenotype was variable in this family, ranging from mild aortic dilation and insufficiency in a 44-year-old woman to overt aortic aneurysm extending from the ascending to the abdominal aorta in a 25-year-old man. None of the affected individuals showed syndromic features, and there was no history of premature stroke or coronary artery disease. Hoffjan et al. (2011) noted that although a different mutation at the R39 residue, R39H, had been associated with type A dissections in 2 families and with type B dissections in another family (Guo et al., 2009), dissections were not observed in the family with the R39C mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 AORTIC ANEURYSM, FAMILIAL THORACIC 6</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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ACTA2, MET49VAL
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<br />
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SNP: rs397515325,
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ClinVar: RCV000055648
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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 German woman who presented with acute aortic dissection at 37 years of age, Hoffjan et al. (2011) identified heterozygosity for a c.145A-G transition in exon 3 of the ACTA2 gene, resulting in a met49-to-val (M49V) substitution at a highly conserved residue in the DNAse-I-binding loop within subdomain 2. The mutation was not found in 192 control chromosomes or in the GenBank dbSNP library. The patient's brother had died at 29 years of age from acute aortic dissection, and her mother, who suffered from slowly progressive spastic paraplegia over 20 years and cancer, died suddenly at 69 years of age in association with a massive drop in blood pressure. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0007 SMOOTH MUSCLE DYSFUNCTION SYNDROME</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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ACTA2, ARG179LEU
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<br />
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SNP: rs387906592,
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ClinVar: RCV001267897
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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 review of the clinical history and outcomes of 33 patients with smooth muscle dysfunction syndrome (SMDYS; 613834), Regalado et al. (2018) found 1 patient who was heterozygous for an arg179-to-leu (R179L) substitution in ACTA2. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0008 SMOOTH MUSCLE DYSFUNCTION SYNDROME</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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ACTA2, ARG179CYS
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<br />
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SNP: rs886039303,
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ClinVar: RCV000255555, RCV000700774, RCV000780814, RCV001265589
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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 2.75-year-old Brazilian girl (patient 7) with smooth muscle dysfunction syndrome (SMDYS; 613834), Moreno et al. (2016) identified heterozygosity for a c.535C-T transition in the ACTA2 gene, resulting in an arg179-to-cys (R179C). The mutation was not found in her unaffected mother; DNA was unavailable from the father. </p><p>In a review of the clinical history and outcomes of 33 patients with SMDYS, Regalado et al. (2018) found 7 patients who were heterozygous for the R179C substitution in ACTA2. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 SMOOTH MUSCLE DYSFUNCTION SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
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|
|
ACTA2, ARG179SER
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<br />
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|
|
SNP: rs886039303,
|
|
|
|
|
|
|
|
ClinVar: RCV001164780
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a review of the clinical history and outcomes of 33 patients with smooth muscle dysfunction syndrome (SMDYS; 613834), Regalado et al. (2018) found 1 patient who was heterozygous for an arg179-to-ser (R179S) substitution in ACTA2. </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>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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|
</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Ades, L. C., Davies, R., Haan, E. A., Holman, K. J., Watson, K. C., Sreetharan, D., Cao, S. N., Milewicz, D. M., Bateman, J. F., Chiodo, A. A., Eccles, M., McNoe, L., Harbord, M.
|
|
<strong>Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.</strong>
|
|
Clin. Dysmorph. 8: 269-276, 1999.
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[PubMed: 10532176]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Brodsky, M. C., Turan, K. E., Khanna, C. L., Patton, A., Kirmani, S.
|
|
<strong>Congenital mydriasis and prune belly syndrome in a child with an ACTA2 mutation.</strong>
|
|
J. AAPOS 18: 393-395, 2014. Note: Erratum: J. AAPOS 18: 518 only, 2014.
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[PubMed: 24998021]
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[Full Text: https://doi.org/10.1016/j.jaapos.2014.02.010]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Guo, D.-C., Pannu, H., Tran-Fadulu, V., Papke, C. L., Yu, R. K., Avidan, N., Bourgeois, S., Estrera, A. L., Safi, H. J., Sparks, E., Amor, D., Ades, L., and 13 others.
|
|
<strong>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</strong>
|
|
Nature Genet. 39: 1488-1493, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008.
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[PubMed: 17994018]
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[Full Text: https://doi.org/10.1038/ng.2007.6]
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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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Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others.
|
|
<strong>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</strong>
|
|
Am. J. Hum. Genet. 84: 617-627, 2009.
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[PubMed: 19409525]
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[Full Text: https://doi.org/10.1016/j.ajhg.2009.04.007]
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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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Hoffjan, S., Waldmuller, S., Blankenfeldt, W., Kotting, J., Gehle, P., Binner, P., Epplen, J. T., Scheffold, T.
|
|
<strong>Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.</strong>
|
|
Europ. J. Hum. Genet. 19: 520-524, 2011.
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[PubMed: 21248741]
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[Full Text: https://doi.org/10.1038/ejhg.2010.239]
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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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Khan, N., Schinzel, A., Shuknecht, B., Baumann, F., Ostergaard, J. R., Yonekawa, Y.
|
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<strong>Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus arteriosus and pupillary dysfunction: a new genetic syndrome?</strong>
|
|
Europ. Neurol. 51: 72-77, 2004.
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[PubMed: 14730227]
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[Full Text: https://doi.org/10.1159/000076248]
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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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Kumar, M. S., Hendrix, J. A., Johnson, A. D., Owens, G. K.
|
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<strong>Smooth muscle alpha-actin gene requires two E-boxes for proper expression in vivo and is a target of class I basic helix-loop-helix proteins.</strong>
|
|
Circ. Res. 92: 840-847, 2003.
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|
[PubMed: 12663487]
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[Full Text: https://doi.org/10.1161/01.RES.0000069031.55281.7C]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Lemire, B. D., Buncic, J. R., Kennedy, S. J., Dyack, S. J., Teebi, A. S.
|
|
<strong>Congenital mydriasis, patent ductus arteriosus, and congenital cystic lung disease: new syndromic spectrum?</strong>
|
|
Am. J. Med. Genet. 131A: 318-319, 2004.
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|
|
[PubMed: 15472996]
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[Full Text: https://doi.org/10.1002/ajmg.a.30341]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., Regalado, E. S.
|
|
<strong>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</strong>
|
|
Am. J. Med. Genet. 152A: 2437-2443, 2010.
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[PubMed: 20734336]
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[Full Text: https://doi.org/10.1002/ajmg.a.33657]
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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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Moreno, C. A., Metze, K., Lomazi, E. A., Bertola, D. R., Barbosa, R. H. A., Cosentino, V., Sobreira, N., Cavalcanti, D. P.
|
|
<strong>Visceral myopathy: clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.</strong>
|
|
Am. J. Med. Genet. 170A: 2965-2974, 2016.
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[PubMed: 27481187]
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[Full Text: https://doi.org/10.1002/ajmg.a.37857]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Regalado, E. S., Mellor-Crummey, L., De Backer, J., Braverman, A. C., Ades, L., Benedict, S., Bradley, T. J., Brickner, M. E., Chatfield, K. C., Child, A., Feist, C., Holmes, K. W., and 18 others.
|
|
<strong>Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.</strong>
|
|
Genet. Med. 20: 1206-1215, 2018.
|
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|
|
[PubMed: 29300374]
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|
[Full Text: https://doi.org/10.1038/gim.2017.245]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Roder, C., Peters, V., Kasuya, H., Nishizawa, T., Wakita, S., Berg, D., Schulte, C., Khan, N., Tatagiba, M., Krischek, B.
|
|
<strong>Analysis of ACTA2 in European Moyamoya disease patients.</strong>
|
|
Europ. J. Paediat. Neurol. 15: 117-122, 2011.
|
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|
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|
|
[PubMed: 20970362]
|
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[Full Text: https://doi.org/10.1016/j.ejpn.2010.09.002]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Shimojima, K., Yamamoto, T.
|
|
<strong>ACTA2 is not a major disease-causing gene for moyamoya disease. (Letter)</strong>
|
|
J. Hum. Genet. 54: 687-688, 2009.
|
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|
|
[PubMed: 19745835]
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[Full Text: https://doi.org/10.1038/jhg.2009.91]
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Ueyama, H., Bruns, G., Kanda, N.
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<strong>Assignment of the vascular smooth muscle actin gene ACTSA to human chromosome 10.</strong>
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Jinrui Idengaku Zasshi 35: 145-150, 1990.
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[Full Text: https://doi.org/10.1007/BF01876459]
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Ueyama, H., Hamada, H., Battula, N., Kakunaga, T.
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<strong>Structure of a human smooth muscle actin gene (aortic type) with a unique intron site.</strong>
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Molec. Cell. Biol. 4: 1073-1078, 1984.
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[PubMed: 6330528]
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[Full Text: https://doi.org/10.1128/mcb.4.6.1073-1078.1984]
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Ueyama, H., Inazawa, J., Ariyama, T., Nishino, H., Ochiai, Y., Ohkubo, I., Miwa, T.
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<strong>Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization.</strong>
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Jpn. J. Hum. Genet. 40: 145-148, 1995.
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Vandekerckhove, J., Weber, K.
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<strong>The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle.</strong>
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Differentiation 14: 123-133, 1979.
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[PubMed: 499690]
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[Full Text: https://doi.org/10.1111/j.1432-0436.1979.tb01021.x]
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Yetman, A. T., Starr, L. J., Bleyl, S. B., Meyers, L., Delaney, J. W.
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<strong>Progressive aortic dilation associated with ACTA2 mutations presenting in infancy.</strong>
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Pediatrics 136: e262-e266, 2015.
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[PubMed: 26034244]
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[Full Text: https://doi.org/10.1542/peds.2014-3032]
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Sonja A. Rasmussen - updated : 01/19/2023<br>Marla J. F. O'Neill - updated : 07/14/2021<br>Ada Hamosh - updated : 05/27/2020<br>Ada Hamosh - updated : 01/15/2020<br>Marla J. F. O'Neill - updated : 09/24/2013<br>Cassandra L. Kniffin - updated : 6/14/2011<br>Ada Hamosh - updated : 3/24/2011<br>Ada Hamosh - updated : 10/6/2009<br>Victor A. McKusick - updated : 12/20/2007<br>Patricia A. Hartz - updated : 3/24/2004
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Victor A. McKusick : 6/4/1986
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