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<title>
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Entry
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- *125660 - DESMIN; DES
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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="row">
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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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<li>
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<a href="/history"> Search History </a>
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</ul>
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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>
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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">*125660</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>
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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 role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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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" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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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/125660">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=ENSG00000175084;t=ENST00000373960" 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=1674" 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=125660" 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=ENSG00000175084;t=ENST00000373960" 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_001382708,NM_001382709,NM_001382710,NM_001382711,NM_001382712,NM_001382713,NM_001927" 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_001927" 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=125660" 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=00514&isoform_id=00514_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/DES" 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/181540,1408188,3411130,3411132,3411134,4378979,6523261,6531404,6686280,11907570,12003119,12003121,19698555,19774203,19908424,21358854,21594664,22415740,23194177,23506465,55749932,55774607,55774609,55774611,62822503,71011040,71011081,71011128,83637999,119591145,119591146,119591147,148728589,194374059,308219100,440355926,440355928,1471766851,1843657965,1843657969,1843658013,1843658029,1843658088,1843658111" 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/P17661" 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=1674" 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=ENSG00000175084;t=ENST00000373960" 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=DES" 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=DES" 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+1674" 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/DES" 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:1674" 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/1674" 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=chr2&hgg_gene=ENST00000373960.4&hgg_start=219418377&hgg_end=219426734&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2770" 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=125660[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=125660[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000175084" 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.gwascentral.org/search?q=DES" 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=DES" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/DES" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DES&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/PA27253" 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:2770" 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:94885" 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/DES#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:94885" 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/1674/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=1674" 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://wormbase.org/db/gene/gene?name=WBGene00002058;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-061027-102" 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">
|
|
<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:1674" 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=DES&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> 1208615009, 770627003<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>
|
|
125660
|
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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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DESMIN; DES
|
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</span>
|
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</h3>
|
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DES" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DES</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/1040?start=-3&limit=10&highlight=1040">2q35</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:219418377-219426734&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'})">2:219,418,377-219,426,734</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>
|
|
<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
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Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=604765,601419,181400" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
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>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/1040?start=-3&limit=10&highlight=1040">
|
|
2q35
|
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</a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Cardiomyopathy, dilated, 1I
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<p>Desmin is the muscle-specific member of the intermediate filament (IF) protein family. It is one of the earliest myogenic markers, both in heart and somites, and is expressed in satellite stem cells and replicating myoblasts. In mature striated muscle, desmin IFs form a 3-dimensional scaffold that appears to extend across the diameter of the myofibril. Desmin IFs surround the Z discs and link the entire contractile apparatus to the sarcolemmal cytoskeleton, cytoplasmic organelles, and nucleus (summary by <a href="#17" class="mim-tip-reference" title="Kouloumenta, A., Mavroidis, M., Capetanaki, Y. <strong>Proper perinuclear localization of the TRIM-like protein myospryn requires its binding partner desmin.</strong> J. Biol. Chem. 282: 35211-35221, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872945</a>] [<a href="https://doi.org/10.1074/jbc.M704733200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872945">Kouloumenta et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872945" 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="#21" class="mim-tip-reference" title="Li, Z., Lilienbaum, A., Butler-Browne, G., Paulin, D. <strong>Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development.</strong> Gene 78: 243-254, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2673923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2673923</a>] [<a href="https://doi.org/10.1016/0378-1119(89)90227-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2673923">Li et al. (1989)</a> determined that the DES gene encodes a 468-amino acid protein that shares structural features with other intermediate filament proteins, including helical domains, a stretch of heptad repeats, and the positions of linkers. Northern blot analysis detected a 2.2-kb transcript in striated skeletal muscle, uterine smooth muscle, and cultured striated muscle cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2673923" 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 human muscle biopsy, <a href="#40" class="mim-tip-reference" title="Vicart, P., Dupret, J.-M., Hazan, J., Li, Z., Gyapay, G., Krishnamoorthy, R., Weissenbach, J., Fardeau, M., Paulin, D. <strong>Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy.</strong> Hum. Genet. 98: 422-429, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8792816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8792816</a>] [<a href="https://doi.org/10.1007/s004390050233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8792816">Vicart et al. (1996)</a> cloned and sequenced the DES gene, which encodes a 469-amino acid protein with a molecular mass of 53 kD. The head domain of desmin, comprising residues 1 to 82, has several putative phosphorylation sites, and the rod domain, comprising residues 83 to 423, contains primarily conserved hydrophobic amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8792816" 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="#38" class="mim-tip-reference" title="Tidball, J. G. <strong>Desmin at myotendinous junctions.</strong> Exp. Cell Res. 199: 206-212, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1544366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1544366</a>] [<a href="https://doi.org/10.1016/0014-4827(92)90425-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1544366">Tidball (1992)</a> found that desmin was codistributed with actin thin filaments within the cellular processes of myotendinous junctions in frog skeletal muscle. Desmin appeared to mediate attachments between the terminal Z disc and the junctional membrane, as well as linking Z discs in series in each sarcomere. In contrast to other cytoskeletal proteins, desmin was located deep in the cellular processes within the filamentous core 30 nm or more from the membrane. <a href="#38" class="mim-tip-reference" title="Tidball, J. G. <strong>Desmin at myotendinous junctions.</strong> Exp. Cell Res. 199: 206-212, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1544366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1544366</a>] [<a href="https://doi.org/10.1016/0014-4827(92)90425-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1544366">Tidball (1992)</a> concluded that desmin provides attachments between the terminal Z disc and membrane-associated proteins to form a force-transmitting system that parallels the thin filaments at myotendinous junctions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1544366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Kusubata, M., Matsuoka, Y., Tsujimura, K., Ito, H., Ando, S., Kamijo, M., Yasuda, H., Ohba, Y., Okumura, E., Kishimoto, T., Inagaki, M. <strong>cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain.</strong> Biochem. Biophys. Res. Commun. 190: 927-934, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8439342/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8439342</a>] [<a href="https://doi.org/10.1006/bbrc.1993.1138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8439342">Kusubata et al. (1993)</a> found that serine/threonine phosphorylation in the head domain of chicken desmin by Cdc2 kinase (<a href="/entry/116940">116940</a>) induced a transition toward the depolymerization of desmin filaments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8439342" 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 yeast 2-hybrid analysis of a human heart cDNA library, <a href="#17" class="mim-tip-reference" title="Kouloumenta, A., Mavroidis, M., Capetanaki, Y. <strong>Proper perinuclear localization of the TRIM-like protein myospryn requires its binding partner desmin.</strong> J. Biol. Chem. 282: 35211-35221, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872945</a>] [<a href="https://doi.org/10.1074/jbc.M704733200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872945">Kouloumenta et al. (2007)</a> found that the N-terminal domain of mouse desmin interacted with the C terminus of human myospryn (CMYA5; <a href="/entry/612193">612193</a>). Reciprocal coimmunoprecipitation experiments and protein pull-down assays with in vitro-translated proteins confirmed direct interaction. Deletion analysis revealed that desmin bound the C-terminal SPRY domain of myospryn. Confocal microscopy of cultured unfused primary mouse cardiomyocytes revealed that the 2 proteins colocalized in a punctate pattern at the nuclear periphery. Western blot analysis of immunoprecipitates of adult mouse heart showed that desmin associated with the lysosome biogenesis complex components dysbindin and pallidin, possibly via its interaction with myospryn. In adult mouse hearts, desmin and myospryn colocalized at intercalated discs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872945" 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="#21" class="mim-tip-reference" title="Li, Z., Lilienbaum, A., Butler-Browne, G., Paulin, D. <strong>Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development.</strong> Gene 78: 243-254, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2673923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2673923</a>] [<a href="https://doi.org/10.1016/0378-1119(89)90227-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2673923">Li et al. (1989)</a> determined that the DES gene contains 9 exons and spans about 8.4 kb. Intronic sequences contain 4 AluI repetitive elements, and the promoter region is G rich. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2673923" 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>Locus control regions (LCRs) are transcriptional regulatory elements, like CpG islands, that establish a transcriptionally competent open chromatin structure. Unlike CpG islands, LCRs have invariably been found linked with tissue-specific genes. <a href="#36" class="mim-tip-reference" title="Tam, J. L. Y., Triantaphyllopoulos, K., Todd, H., Raguz, S., de Wit, T., Morgan, J. E., Partridge, T. A., Makrinou, E., Grosveld, F., Antoniou, M. <strong>The human desmin locus: gene organization and LCR-mediated transcriptional control.</strong> Genomics 87: 733-746, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16545539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16545539</a>] [<a href="https://doi.org/10.1016/j.ygeno.2006.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16545539">Tam et al. (2006)</a> identified a muscle-specific LCR linked to the DES gene. The DES LCR is a complex multicomponent element located within 18 kb 5-prime of the DES transcriptional start site. <a href="#36" class="mim-tip-reference" title="Tam, J. L. Y., Triantaphyllopoulos, K., Todd, H., Raguz, S., de Wit, T., Morgan, J. E., Partridge, T. A., Makrinou, E., Grosveld, F., Antoniou, M. <strong>The human desmin locus: gene organization and LCR-mediated transcriptional control.</strong> Genomics 87: 733-746, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16545539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16545539</a>] [<a href="https://doi.org/10.1016/j.ygeno.2006.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16545539">Tam et al. (2006)</a> identified 2 genes immediately downstream of DES, SPEG and APEG1 (see <a href="/entry/615950">615950</a>), that are also preferentially expressed in muscle, and they suggested that the DES LCR may form a functional expression module involved in regulating expression of all 3 genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16545539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By use of cDNA clones of desmin in somatic cell hybrids, <a href="#31" class="mim-tip-reference" title="Quax, W., Meera Khan, P., Quax-Jeuken, Y., Bloemendal, H. <strong>The human desmin and vimentin genes are located on different chromosomes.</strong> Gene 38: 189-196, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4065572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4065572</a>] [<a href="https://doi.org/10.1016/0378-1119(85)90217-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4065572">Quax et al. (1985)</a> assigned the DES gene to chromosome 2. By in situ hybridization, <a href="#41" class="mim-tip-reference" title="Viegas-Pequignot, E., Lin, L. Z., Dutrillaux, B., Apiou, F., Paulin, D. <strong>Assignment of human desmin gene to band 2q35 by nonradioactive in situ hybridization.</strong> Hum. Genet. 83: 33-36, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2670738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2670738</a>] [<a href="https://doi.org/10.1007/BF00274143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2670738">Viegas-Pequignot et al. (1989)</a> localized the gene to 2q35. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2670738+4065572" 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 the mouse, <a href="#13" class="mim-tip-reference" title="Jankowski, S. A., Gumucio, D. L. <strong>Genes for tensin, villin and desmin are linked on mouse chromosome 1.</strong> Mammalian Genome 6: 744-745, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8563175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8563175</a>] [<a href="https://doi.org/10.1007/BF00354299" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8563175">Jankowski and Gumucio (1995)</a> demonstrated that the genes for tensin (<a href="/entry/600076">600076</a>), villin (<a href="/entry/193040">193040</a>), and desmin are closely linked on chromosome 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8563175" 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>Myofibrillar Myopathy 1</em></strong></p><p>
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<a href="#8" class="mim-tip-reference" title="Goldfarb, L. G., Park, K.-Y., Cervenakova, L., Gorokhova, S., Lee, H.-S., Vasconcelos, O., Nagle, J. W., Semino-Mora, C., Sivakumar, K., Dalakas, M. C. <strong>Missense mutations in desmin associated with familial cardiac and skeletal myopathy.</strong> Nature Genet. 19: 402-403, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697706</a>] [<a href="https://doi.org/10.1038/1300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9697706">Goldfarb et al. (1998)</a> reported 2 families with desmin-related cardioskeletal myopathy (MFM1; <a href="/entry/601419">601419</a>) associated with mutations in the highly conserved C-terminal portion of the desmin rod domain. A heterozygous (<a href="#0001">125660.0001</a>) mutation was found in a family with an adult-onset skeletal myopathy and mild cardiac involvement. Compound heterozygosity for 2 other desmin mutations (<a href="#0002">125660.0002</a>; <a href="#0003">125660.0003</a>) was detected in a second family with a childhood-onset aggressive course of cardiac and skeletal myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9697706" 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="#7" class="mim-tip-reference" title="Dalakas, M. C., Park, K.-Y., Semino-Mora, C., Lee, H. S., Sivakumar, K., Goldfarb, L. G. <strong>Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene.</strong> New Eng. J. Med. 342: 770-780, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10717012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10717012</a>] [<a href="https://doi.org/10.1056/NEJM200003163421104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10717012">Dalakas et al. (2000)</a> searched for mutations in the desmin gene in 22 patients from 8 families with dominantly inherited myofibrillar or desmin-related myopathy and 2 patients with sporadic disease. They identified mutations in 12 patients (10 from 4 families and 2 sporadic), 7 of whom had cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10717012" 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="#16" class="mim-tip-reference" title="Kaminska, A., Strelkov, S. V., Goudeau, B., Olive, M., Dagvadorj, A., Fidzianska, A., Simon-Cateras, M., Shatunov, A., Dalakas, M. C., Ferrer, I., Kwiecinski, H., Vicart, P., Goldfarb, L. G. <strong>Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy.</strong> Hum. Genet. 114: 306-313, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14648196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14648196</a>] [<a href="https://doi.org/10.1007/s00439-003-1057-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14648196">Kaminska et al. (2004)</a> studied 3 families with skeletal or cardioskeletal myopathy caused by small in-frame deletions in the desmin gene. Two Polish families with skeletal myopathy without cardiac involvement had an in-frame deletion of 3 amino acids (<a href="#0012">125660.0012</a>) in an area known to be conserved in evolution. An affected Spanish family had a single amino acid deletion (<a href="#0013">125660.0013</a>). <a href="#16" class="mim-tip-reference" title="Kaminska, A., Strelkov, S. V., Goudeau, B., Olive, M., Dagvadorj, A., Fidzianska, A., Simon-Cateras, M., Shatunov, A., Dalakas, M. C., Ferrer, I., Kwiecinski, H., Vicart, P., Goldfarb, L. G. <strong>Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy.</strong> Hum. Genet. 114: 306-313, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14648196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14648196</a>] [<a href="https://doi.org/10.1007/s00439-003-1057-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14648196">Kaminska et al. (2004)</a> showed that these small deletions disturbed the coiled-coil structure of desmin in a highly specific way. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14648196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 unrelated probands with desmin-related myopathy, <a href="#3" class="mim-tip-reference" title="Bar, H., Goudeau, B., Walde, S., Casteras-Simon, M., Mucke, N., Shatunov, A., Goldberg, Y. P., Clarke, C., Holton, J. L., Eymard, B., Katus, H. A., Fardeau, M., Goldfarb, L., Vicart, P., Herrmann, H. <strong>Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies.</strong> Hum. Mutat. 28: 374-386, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17221859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17221859</a>] [<a href="https://doi.org/10.1002/humu.20459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17221859">Bar et al. (2007)</a> identified 3 novel mutations in the DES gene (see, e.g., <a href="#0015">125660.0015</a>) located in the non-alpha-helical C-terminal tail domain of the protein. All had severe skeletal and cardiac muscle involvement. Functional expression studies of these and other tail domain pathogenic mutations revealed that different mutations in the tail region had different functional effects. Although some mutant proteins were unable to assemble into filaments, most formed filaments with altered viscometric properties and/or impaired ability to assemble properly with wildtype desmin. <a href="#3" class="mim-tip-reference" title="Bar, H., Goudeau, B., Walde, S., Casteras-Simon, M., Mucke, N., Shatunov, A., Goldberg, Y. P., Clarke, C., Holton, J. L., Eymard, B., Katus, H. A., Fardeau, M., Goldfarb, L., Vicart, P., Herrmann, H. <strong>Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies.</strong> Hum. Mutat. 28: 374-386, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17221859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17221859</a>] [<a href="https://doi.org/10.1002/humu.20459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17221859">Bar et al. (2007)</a> suggested that desmin tail mutations can affect multiple pathways, including mechanochemical signaling, intracellular transport, and interactions with other proteins, resulting in distinct cellular malfunctions and variable clinical phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17221859" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 distantly related Dutch families segregating autosomal dominant desmin-related myopathy with a highly heterogeneous clinical picture, varying from isolated dilated cardiomyopathy to more generalized skeletal myopathy and mild respiratory problems, <a href="#5" class="mim-tip-reference" title="Bergman, J. E. H., Veenstra-Knol, H. E., van Essen, A. J., van Ravenswaaij, C. M. A., den Dunnen, W. F. A., van den Wijngaard, A., van Tintelen, J. P. <strong>Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.</strong> Europ. J. Med. Genet. 50: 355-366, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17720647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17720647</a>] [<a href="https://doi.org/10.1016/j.ejmg.2007.06.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17720647">Bergman et al. (2007)</a> identified heterozygosity for a missense mutation in the DES gene (S13F; <a href="#0019">125660.0019</a>) that was not present in unaffected family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17720647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 affected members of a 2-generation Chinese family with desmin-related myopathy, <a href="#29" class="mim-tip-reference" title="Pica, E. C., Kathirvel, P., Pramono, Z. A. D., Lai, P.-S., Yee, W.-C. <strong>Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family.</strong> Neuromusc. Disord. 18: 178-182, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18061454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18061454</a>] [<a href="https://doi.org/10.1016/j.nmd.2007.09.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18061454">Pica et al. (2008)</a> identified heterozygosity for the S13F mutation in the DES gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18061454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="van Tintelen, J. P., Van Gelder, I. C., Asimaki, A., Suurmeijer, A. J. H., Wiesfeld, A. C. P., Jongbloed, J. D. H., van den Wijngaard, A., Kuks, J. B. M., van Spaendonck-Zwarts, K. Y., Notermans, N., Boven, L., van den Heuvel, F., Veenstra-Knol, H. E., Saffitz, J. E., Hofstra, R. M. W., van den Berg, M. P. <strong>Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene.</strong> Heart Rhythm 6: 1574-1583, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19879535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19879535</a>] [<a href="https://doi.org/10.1016/j.hrthm.2009.07.041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19879535">Van Tintelen et al. (2009)</a> restudied the Dutch kindred with MFM1 reported by <a href="#5" class="mim-tip-reference" title="Bergman, J. E. H., Veenstra-Knol, H. E., van Essen, A. J., van Ravenswaaij, C. M. A., den Dunnen, W. F. A., van den Wijngaard, A., van Tintelen, J. P. <strong>Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.</strong> Europ. J. Med. Genet. 50: 355-366, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17720647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17720647</a>] [<a href="https://doi.org/10.1016/j.ejmg.2007.06.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17720647">Bergman et al. (2007)</a> and expanded it to include 3 distantly related families. The authors described 2 more affected Dutch families whose ancestors could be traced to the same small, poorly populated region in which the common ancestral couple of the large Dutch kindred had lived. All 27 affected individuals were heterozygous for the DES S13F mutation; based on haplotype analysis, the mutation was estimated to be between 220 and 495 years old. Immunofluorescence analysis of patient myocardia showed normal amounts of the major desmosomal proteins, but intercalated discs were more convoluted and elongated and had a zigzag appearance compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17720647+19879535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Pinol-Ripoll, G., Shatunov, A., Cabello, A., Larrode, P., de la Puerta, I., Pelegrin, J., Ramos, F. J., Olive, M., Goldfarb, L. G. <strong>Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin.</strong> Neuromusc. Disord. 19: 418-422, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19433360[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.nmd.2009.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433360">Pinol-Ripoll et al. (2009)</a> reported a female patient with recurrent episodes of syncope from infancy and an aggressive course leading to the devastation of cardiac, skeletal, and smooth musculature and death from cardiac failure at age 20 years, in whom they identified homozygosity for a 21-bp deletion in the desmin gene (<a href="#0004">125660.0004</a>). <a href="#30" class="mim-tip-reference" title="Pinol-Ripoll, G., Shatunov, A., Cabello, A., Larrode, P., de la Puerta, I., Pelegrin, J., Ramos, F. J., Olive, M., Goldfarb, L. G. <strong>Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin.</strong> Neuromusc. Disord. 19: 418-422, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19433360[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.nmd.2009.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433360">Pinol-Ripoll et al. (2009)</a> stated that this was the first reported case of infantile-onset desmin-associated cardiopathy, and noted that their patient had the same mutation previously identified by <a href="#25" class="mim-tip-reference" title="Munoz-Marmol, A. M., Strasser, G., Isamat, M., Coulombe, P. A., Yang, Y., Roca, X., Vela, E., Mate, J. L., Coll, J., Fernandez-Figueras, M. T., Navas-Palacios, J. J., Ariza, A., Fuchs, E. <strong>A dysfunctional desmin mutation in a patient with severe generalized myopathy.</strong> Proc. Nat. Acad. Sci. 95: 11312-11317, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9736733[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/10.1073/pnas.95.19.11312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9736733">Munoz-Marmol et al. (1998)</a> in a 15-year-old boy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19433360+9736733" 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 Dutch patient with desmin-related myopathy and arrhythmogenic right ventricular cardiomyopathy (ARVC), <a href="#26" class="mim-tip-reference" title="Otten, E., Asimaki, A., Maass, A., van Langen, I. M., van der Wal, A., de Jonge, N., van den Berg, M. P., Saffitz, J. E., Wilde, A. A. M., Jongbloed, J. D. H., van Tintelen, J. P. <strong>Desmin mutations as a cause of right ventricular heart failure affect the intercalated disks.</strong> Heart Rhythm 7: 1058-1064, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20423733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20423733</a>] [<a href="https://doi.org/10.1016/j.hrthm.2010.04.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20423733">Otten et al. (2010)</a> identified heterozygosity for a missense mutation in the DES gene (N342D; <a href="#0020">125660.0020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20423733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a large Swedish family segregating autosomal dominant MFM1 and ARVC, <a href="#11" class="mim-tip-reference" title="Hedberg, C., Melberg, A., Kuhl, A., Jenne, D., Oldfors, A. <strong>Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation.</strong> Europ. J. Hum. Genet. 20: 984-985, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22395865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22395865</a>] [<a href="https://doi.org/10.1038/ejhg.2012.39" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22395865">Hedberg et al. (2012)</a> identified a heterozygous P419S mutation (<a href="#0017">125660.0017</a>) in the DES gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22395865" 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 2 Turkish sibs, born of consanguineous parents, with what the authors called autosomal recessive limb-girdle muscular dystrophy (LGMD2R), <a href="#6" class="mim-tip-reference" title="Cetin, N., Balci-Hayta, B., Gundesli, H., Korkusuz, P., Purali, N., Talim, B., Tan, E., Selcen, D., Erdem-Ozdamar, S., Dincer, P. <strong>A novel desmin mutation leading to autosomal recessive limb-girdle muscular dystrophy: distinct histopathological outcomes compared with desminopathies.</strong> J. Med. Genet. 50: 437-443, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687351</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-101487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687351">Cetin et al. (2013)</a> identified a homozygous splice site mutation in the DES gene (<a href="#0018">125660.0018</a>). LGMD2R was later reclassified as a form of myofibrillar myopathy by <a href="#34" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>. The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder and was not found in several control databases. The mutant protein was expressed in patient skeletal muscle, which had normal myofibrillar organization, but confocal laser scanning microscopy showed a disruption in binding between desmin and lamin B (LMNB1; <a href="/entry/150340">150340</a>). The patients had onset in their teens or twenties of progressive proximal muscle weakness and atrophy affecting the upper and lower limbs. Neither patient had evidence of a cardiomyopathy, and muscle biopsy showed dystrophic changes without protein aggregates or myofibrillar myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+23687351" 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>Dilated Cardiomyopathy 1I</em></strong></p><p>
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<a href="#19" class="mim-tip-reference" title="Li, D., Tapscoft, T., Gonzalez, O., Burch, P. E., Quinones, M. A., Zoghbi, W. A., Hill, R., Bachinski, L. L., Mann, D. L., Roberts, R. <strong>Desmin mutation responsible for idiopathic dilated cardiomyopathy.</strong> Circulation 100: 461-464, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10430757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10430757</a>] [<a href="https://doi.org/10.1161/01.cir.100.5.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10430757">Li et al. (1999)</a> used a candidate gene approach to identify genetic defects in 44 unrelated probands with autosomal dominant dilated cardiomyopathy. In 1 family with pure cardiomyopathy without skeletal myopathy (CMD1I; <a href="/entry/604765">604765</a>), they identified a heterozygous ile451-to-met mutation in the DES gene (<a href="#0005">125660.0005</a>). The reports of <a href="#8" class="mim-tip-reference" title="Goldfarb, L. G., Park, K.-Y., Cervenakova, L., Gorokhova, S., Lee, H.-S., Vasconcelos, O., Nagle, J. W., Semino-Mora, C., Sivakumar, K., Dalakas, M. C. <strong>Missense mutations in desmin associated with familial cardiac and skeletal myopathy.</strong> Nature Genet. 19: 402-403, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697706</a>] [<a href="https://doi.org/10.1038/1300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9697706">Goldfarb et al. (1998)</a> and <a href="#19" class="mim-tip-reference" title="Li, D., Tapscoft, T., Gonzalez, O., Burch, P. E., Quinones, M. A., Zoghbi, W. A., Hill, R., Bachinski, L. L., Mann, D. L., Roberts, R. <strong>Desmin mutation responsible for idiopathic dilated cardiomyopathy.</strong> Circulation 100: 461-464, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10430757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10430757</a>] [<a href="https://doi.org/10.1161/01.cir.100.5.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10430757">Li et al. (1999)</a> suggested a distinct cardiac genotype-phenotype correlation for mutations in the DES gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10430757+9697706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Miyamoto, Y., Akita, H., Shiga, N., Takai, E., Iwai, C., Mizutani, K., Kawai, H., Takarada, A., Yokoyama, M. <strong>Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population.</strong> Europ. Heart J. 22: 2284-2289, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11728149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11728149</a>] [<a href="https://doi.org/10.1053/euhj.2001.2836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11728149">Miyamoto et al. (2001)</a> screened exon 8 of the DES gene in a cohort of 265 Japanese probands with dilated cardiomyopathy and identified 3 unrelated men who were heterozygous for the previously reported I451M mutation. None of the 3 patients showed any clinical evidence of skeletal muscle involvement on physical examination, and none had abnormal serum levels of creatine kinase or a myopathic pattern on electromyelogram. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11728149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Taylor, M. R. G., Slavov, D., Ku, L., Di Lenarda, A., Sinagra, G., Carniel, E., Haubold, K., Boucek, M. M., Ferguson, D., Graw, S. L., Zhu, X., Cavanaugh, J., Sucharov, C. C., Long, C. S., Bristow, M. R., Lavori, P., Maestroni, L., BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank. <strong>Prevalence of desmin mutations in dilated cardiomyopathy.</strong> Circulation 115: 1244-1251, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17325244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17325244</a>] [<a href="https://doi.org/10.1161/CIRCULATIONAHA.106.646778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17325244">Taylor et al. (2007)</a> analyzed the DES gene in 425 probands with dilated cardiomyopathy and identified 5 missense mutations in 6 sporadic patients, 3 of which were likely pathogenic (see, e.g., <a href="#0021">125660.0021</a>). None of the patients had overt skeletal muscle involvement, although none had a skeletal muscle biopsy and formal neurologic assessment was not performed in most patients. Functional analysis of the 3 likely pathogenic mutations demonstrated severe disruption of desmin filament assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17325244" 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>Neurogenic Scapuloperoneal Syndrome, Kaeser Type</em></strong></p><p>
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In a large, multigenerational kindred with scapuloperoneal weakness and atrophy (SCPNK; <a href="/entry/181400">181400</a>) originally described by Kaeser (<a href="#14" class="mim-tip-reference" title="Kaeser, H. E. <strong>Die familiaere scapuloperoneale Muskelatrophie.</strong> Dtsch. Z. Nervenheilk. 186: 379-394, 1964."None>1964</a>, <a href="#15" class="mim-tip-reference" title="Kaeser, H. E. <strong>Scapuloperoneal muscular atrophy.</strong> Brain 88: 407-418, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5828910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5828910</a>] [<a href="https://doi.org/10.1093/brain/88.2.407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5828910">1965</a>), <a href="#42" class="mim-tip-reference" title="Walter, M. C., Reilich, P., Huebner, A., Fischer, D., Schroder, R., Vorgerd, M., Kress, W., Born, C., Schoser, B. G., Krause, K. H., Klutzny, U. Bulst, S. Frey, J. R., Lochmuller, H. <strong>Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.</strong> Brain 130: 1485-1496, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17439987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17439987</a>] [<a href="https://doi.org/10.1093/brain/awm039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17439987">Walter et al. (2007)</a> detected a heterozygous missense mutation (<a href="#0016">125660.0016</a>) in the DES gene in all affected members. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17439987+5828910" 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="#43" class="mim-tip-reference" title="Wieneke, S., Stehle, R., Li, Z., Jockusch, H. <strong>Generation of tension by skinned fibers and intact skeletal muscles from desmin-deficient mice.</strong> Biochem. Biophys. Res. Commun. 278: 419-425, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11097852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11097852</a>] [<a href="https://doi.org/10.1006/bbrc.2000.3810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11097852">Wieneke et al. (2000)</a> generated Des-null mice and found that desmin is not essential for acute tensile strength, but rather for optimal activation of intact myofibers during excitation-contraction coupling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11097852" 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="#20" class="mim-tip-reference" title="Li, Z., Colucci-Guyon, E., Pincon-Raymond, M., Mericskay, M., Pournin, S., Paulin, D., Babinet, C. <strong>Cardiovascular lesions and skeletal myopathy in mice lacking desmin.</strong> Dev. Biol. 175: 362-366, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626040</a>] [<a href="https://doi.org/10.1006/dbio.1996.0122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8626040">Li et al. (1996)</a> developed desmin-null mice. Despite the complete lack of desmin, mutant mice developed and reproduced. Skeletal, cardiac, and smooth muscle formed in mutant mice, but morphologic abnormalities were observed in the diaphragm of adult mice. These abnormalities were characterized by disorganized, distended, and nonaligned fibers. The hearts of mutant mice presented areas of hemorrhage in which fibrosis and ischemia were observed. The absence of desmin also produced defects in smooth muscles. <a href="#20" class="mim-tip-reference" title="Li, Z., Colucci-Guyon, E., Pincon-Raymond, M., Mericskay, M., Pournin, S., Paulin, D., Babinet, C. <strong>Cardiovascular lesions and skeletal myopathy in mice lacking desmin.</strong> Dev. Biol. 175: 362-366, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626040</a>] [<a href="https://doi.org/10.1006/dbio.1996.0122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8626040">Li et al. (1996)</a> concluded that desmin is not required for myogenic commitment or for myoblast fusion and differentiation of skeletal, cardiac, and smooth muscle, but it is essential to strengthen and maintain the integrity of these tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8626040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using analytical ultracentrifugation, viscometry, and time-lapse electron microscopy, <a href="#4" class="mim-tip-reference" title="Bar, H., Mucke, N., Kostareva, A., Sjoberg, G., Aebi, U., Herrmann, H. <strong>Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages.</strong> Proc. Nat. Acad. Sci. 102: 15099-15104, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16217025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16217025</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16217025[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/10.1073/pnas.0504568102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16217025">Bar et al. (2005)</a> examined how myopathy-associated mutations within the alpha-helical rod domain of mouse desmin affected distinct phases of intermediate filament assembly. Whereas 6 of the 14 mutants allowed assembly of desmin into normal filaments in vitro, the other mutants interfered with the assembly process at distinct stages, i.e., tetramer formation, unit-length filament formation, filament elongation, and intermediate filament maturation. Mutants with in vitro assembly defects yielded dot-like aggregates in transfected cells, whereas mutants that formed filaments in vitro formed seemingly normal cytoskeletal intermediate filaments following transfection into vimentin (<a href="/entry/193060">193060</a>)-free human adrenocortical carcinoma cells or vimentin-positive mouse fibroblasts. <a href="#4" class="mim-tip-reference" title="Bar, H., Mucke, N., Kostareva, A., Sjoberg, G., Aebi, U., Herrmann, H. <strong>Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages.</strong> Proc. Nat. Acad. Sci. 102: 15099-15104, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16217025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16217025</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16217025[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/10.1073/pnas.0504568102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16217025">Bar et al. (2005)</a> concluded that the degree of assembly defect of a mutant desmin variant in vitro does not correlate directly with disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16217025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By immunohistochemical analysis of wildtype and Des -/- mouse hearts, <a href="#17" class="mim-tip-reference" title="Kouloumenta, A., Mavroidis, M., Capetanaki, Y. <strong>Proper perinuclear localization of the TRIM-like protein myospryn requires its binding partner desmin.</strong> J. Biol. Chem. 282: 35211-35221, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872945</a>] [<a href="https://doi.org/10.1074/jbc.M704733200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872945">Kouloumenta et al. (2007)</a> found that Des knockout resulted in abnormalities at the intercalated discs. In primary mouse cardiomyocytes, Des knockout resulted in mislocalization of lysosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872945" 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>.0001 MYOPATHY, MYOFIBRILLAR, 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs59962885 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs59962885;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/rs59962885?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=rs59962885" 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=rs59962885" 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=RCV000056762 OR RCV000856836 OR RCV002265557" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056762, RCV000856836, RCV002265557" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056762...</a>
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<p>In affected members of a family with adult-onset myofibrillar myopathy-1 (MFM1; <a href="/entry/601419">601419</a>) and mild cardiac involvement, <a href="#8" class="mim-tip-reference" title="Goldfarb, L. G., Park, K.-Y., Cervenakova, L., Gorokhova, S., Lee, H.-S., Vasconcelos, O., Nagle, J. W., Semino-Mora, C., Sivakumar, K., Dalakas, M. C. <strong>Missense mutations in desmin associated with familial cardiac and skeletal myopathy.</strong> Nature Genet. 19: 402-403, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697706</a>] [<a href="https://doi.org/10.1038/1300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9697706">Goldfarb et al. (1998)</a> identified a heterozygous G-to-C transversion in exon 5 of the DES gene, resulting in an ala337-to-pro (A337P) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9697706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002265558" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002265558" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002265558</a>
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<p>In 3 of 4 sibs affected with a severe childhood-onset form of cardioskeletal myopathy (MFM1; <a href="/entry/601419">601419</a>), <a href="#8" class="mim-tip-reference" title="Goldfarb, L. G., Park, K.-Y., Cervenakova, L., Gorokhova, S., Lee, H.-S., Vasconcelos, O., Nagle, J. W., Semino-Mora, C., Sivakumar, K., Dalakas, M. C. <strong>Missense mutations in desmin associated with familial cardiac and skeletal myopathy.</strong> Nature Genet. 19: 402-403, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697706</a>] [<a href="https://doi.org/10.1038/1300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9697706">Goldfarb et al. (1998)</a> identified compound heterozygosity for 2 mutations in the DES gene: a G-to-C transversion in exon 6, resulting in an ala360-to-pro (A360P) substitution, and an A-to-T transversion in exon 6, resulting in an asn393-to-ile (N393I) substitution (<a href="#0003">125660.0003</a>). Several older unaffected members of the family who were beyond the maximal age of disease onset had 1 of these mutations; the 55-year-old mother of the affected sibs and her 54-year-old sister showed the A360P mutation, and a 66-year-old paternal uncle carried the N393I mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9697706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056778 OR RCV002265559 OR RCV003162255" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056778, RCV002265559, RCV003162255" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056778...</a>
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<p>For discussion of the asn393-to-ile (N393I) mutation in the DES gene that was found in compound heterozygous state in patients with severe childhood-onset myofibrillar myopathy-1 (MFM1; <a href="/entry/601419">601419</a>) by <a href="#8" class="mim-tip-reference" title="Goldfarb, L. G., Park, K.-Y., Cervenakova, L., Gorokhova, S., Lee, H.-S., Vasconcelos, O., Nagle, J. W., Semino-Mora, C., Sivakumar, K., Dalakas, M. C. <strong>Missense mutations in desmin associated with familial cardiac and skeletal myopathy.</strong> Nature Genet. 19: 402-403, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697706</a>] [<a href="https://doi.org/10.1038/1300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9697706">Goldfarb et al. (1998)</a>, see <a href="#0002">125660.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9697706" 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">rs60538473 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs60538473;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=rs60538473" 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=rs60538473" 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=RCV000056803 OR RCV002265560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056803, RCV002265560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056803...</a>
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<p>In a patient with severe generalized myopathy (MFM1; <a href="/entry/601419">601419</a>) reported by <a href="#1" class="mim-tip-reference" title="Ariza, A., Coll, J., Fernandez-Figueras, M. T., Lopez, M. D., Mate, J. L., Garcia, O., Fernandez-Vasalo, A., Navas-Palacios, J. J. <strong>Desmin myopathy: a multisystem disorder involving skeletal, cardiac, and smooth muscle.</strong> Hum. Path. 26: 1032-1037, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7672786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7672786</a>] [<a href="https://doi.org/10.1016/0046-8177(95)90095-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7672786">Ariza et al. (1995)</a>, <a href="#25" class="mim-tip-reference" title="Munoz-Marmol, A. M., Strasser, G., Isamat, M., Coulombe, P. A., Yang, Y., Roca, X., Vela, E., Mate, J. L., Coll, J., Fernandez-Figueras, M. T., Navas-Palacios, J. J., Ariza, A., Fuchs, E. <strong>A dysfunctional desmin mutation in a patient with severe generalized myopathy.</strong> Proc. Nat. Acad. Sci. 95: 11312-11317, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9736733[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/10.1073/pnas.95.19.11312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9736733">Munoz-Marmol et al. (1998)</a> identified a homozygous 21-bp deletion in the DES gene, predicting a mutant desmin protein lacking 7 amino acids, residues arg173 to glu179. <a href="#25" class="mim-tip-reference" title="Munoz-Marmol, A. M., Strasser, G., Isamat, M., Coulombe, P. A., Yang, Y., Roca, X., Vela, E., Mate, J. L., Coll, J., Fernandez-Figueras, M. T., Navas-Palacios, J. J., Ariza, A., Fuchs, E. <strong>A dysfunctional desmin mutation in a patient with severe generalized myopathy.</strong> Proc. Nat. Acad. Sci. 95: 11312-11317, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9736733[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/10.1073/pnas.95.19.11312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9736733">Munoz-Marmol et al. (1998)</a> provided functional analysis to demonstrate that this mutation severely compromised the ability of desmin to assemble into intermediate filaments in vivo and in vitro. In desmin-null mice, myofibrils are fragile upon mechanical stress, and muscle weakness develops with age. This mechanical-sensitive aspect of the phenotype was evident in the patient, who developed muscle weakness in his teens. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7672786+9736733" 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 female patient who had recurrent episodes of syncope from infancy and an aggressive course leading to the devastation of cardiac, skeletal, and smooth musculature and death from cardiac failure at age 20 years, <a href="#30" class="mim-tip-reference" title="Pinol-Ripoll, G., Shatunov, A., Cabello, A., Larrode, P., de la Puerta, I., Pelegrin, J., Ramos, F. J., Olive, M., Goldfarb, L. G. <strong>Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin.</strong> Neuromusc. Disord. 19: 418-422, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19433360[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.nmd.2009.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433360">Pinol-Ripoll et al. (2009)</a> identified homozygosity for the same 21-bp deletion in the DES gene. Her consanguineous unaffected parents were each heterozygous for the mutation. <a href="#30" class="mim-tip-reference" title="Pinol-Ripoll, G., Shatunov, A., Cabello, A., Larrode, P., de la Puerta, I., Pelegrin, J., Ramos, F. J., Olive, M., Goldfarb, L. G. <strong>Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin.</strong> Neuromusc. Disord. 19: 418-422, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19433360[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.nmd.2009.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433360">Pinol-Ripoll et al. (2009)</a> stated that this was the youngest known molecularly identified patient with desminopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19433360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 CARDIOMYOPATHY, DILATED, 1I</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913002 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913002;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/rs121913002?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=rs121913002" 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=rs121913002" 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=RCV000018318 OR RCV000056787 OR RCV000698481 OR RCV002265561 OR RCV004018640" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018318, RCV000056787, RCV000698481, RCV002265561, RCV004018640" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018318...</a>
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<p>In a family with autosomal dominant pure dilated cardiomyopathy (CMD1I; <a href="/entry/604765">604765</a>), <a href="#19" class="mim-tip-reference" title="Li, D., Tapscoft, T., Gonzalez, O., Burch, P. E., Quinones, M. A., Zoghbi, W. A., Hill, R., Bachinski, L. L., Mann, D. L., Roberts, R. <strong>Desmin mutation responsible for idiopathic dilated cardiomyopathy.</strong> Circulation 100: 461-464, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10430757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10430757</a>] [<a href="https://doi.org/10.1161/01.cir.100.5.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10430757">Li et al. (1999)</a> identified a heterozygous C-to-G transversion at nucleotide 1353 of the DES gene, resulting in an ile451-to-met substitution. This mutation was not present in 920 control chromosomes. The residue involved is located in the carboxy tail domain of the protein, suggesting an important functional role for this region in cardiac myocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10430757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Miyamoto, Y., Akita, H., Shiga, N., Takai, E., Iwai, C., Mizutani, K., Kawai, H., Takarada, A., Yokoyama, M. <strong>Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population.</strong> Europ. Heart J. 22: 2284-2289, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11728149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11728149</a>] [<a href="https://doi.org/10.1053/euhj.2001.2836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11728149">Miyamoto et al. (2001)</a> screened exon 8 of the DES gene in a cohort of 265 Japanese probands with dilated cardiomyopathy and identified 3 unrelated men who were heterozygous for the I451M substitution. None of the 3 patients showed any clinical evidence of skeletal muscle involvement on physical examination, and none had abnormal levels of creatine kinase or a myopathic pattern on electromyelogram. All 3 cases were sporadic; in the 1 family in which parental DNA was available, the mutation was shown to have arisen de novo. Haplotype analysis indicated that 2 of the men might have been ancestrally related. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11728149" 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">rs57639980 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57639980;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=rs57639980" 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=rs57639980" 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=RCV000056765 OR RCV001044194" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056765, RCV001044194" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056765...</a>
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<p>In affected members of a large, 6-generation Ashkenazi Jewish family with desmin-related myopathy (MFM1; <a href="/entry/601419">601419</a>) reported by <a href="#12" class="mim-tip-reference" title="Horowitz, S. H., Schmalbruch, H. <strong>Autosomal dominant distal myopathy with desmin storage: a clinicopathologic and electrophysiologic study of a large kinship.</strong> Muscle Nerve 17: 151-160, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8114783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8114783</a>] [<a href="https://doi.org/10.1002/mus.880170204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8114783">Horowitz and Schmalbruch (1994)</a>, <a href="#33" class="mim-tip-reference" title="Sjoberg, G., Saavedra-Matiz, C. A., Rosen, D. R., Wijsman, E. M., Borg, K., Horowitz, S. H., Sejersen, T. <strong>A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation.</strong> Hum. Molec. Genet. 8: 2191-2198, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545598</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545598">Sjoberg et al. (1999)</a> identified what they claimed to be the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The leu345-to-pro mutation (L345P) in this kindred was located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin was incapable of forming filamentous networks in transfected HeLa and SW13 cells. <a href="#33" class="mim-tip-reference" title="Sjoberg, G., Saavedra-Matiz, C. A., Rosen, D. R., Wijsman, E. M., Borg, K., Horowitz, S. H., Sejersen, T. <strong>A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation.</strong> Hum. Molec. Genet. 8: 2191-2198, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545598</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545598">Sjoberg et al. (1999)</a> concluded that the L345P mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8114783+10545598" 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">rs121913003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913003;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=rs121913003" 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=rs121913003" 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=RCV000056781 OR RCV000627795 OR RCV001787806 OR RCV001798009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056781, RCV000627795, RCV001787806, RCV001798009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056781...</a>
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<p>In a sporadic case of cardiac and skeletal myopathy (MFM1; <a href="/entry/601419">601419</a>), <a href="#28" class="mim-tip-reference" title="Park, K.-Y., Dalakas, M. C., Semino-Mora, C., Lee, H.-S., Litvak, S., Takeda, K., Ferrans, V. J., Goldfarb, L. G. <strong>Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation.</strong> Clin. Genet. 57: 423-429, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10905661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10905661</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2000.570604.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10905661">Park et al. (2000)</a> demonstrated heterozygosity for an arg406-to-trp (R406W) mutation in the DES gene. The mutation was not found in the patient's father, mother, or sister. Alternative paternity was excluded. Haplotype analysis indicated that the patient's father was a germline mosaic for the desmin mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10905661" 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">rs267607483 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607483;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=rs267607483" 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=rs267607483" 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=RCV000056810 OR RCV000154574 OR RCV001233592 OR RCV002381361" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056810, RCV000154574, RCV001233592, RCV002381361" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056810...</a>
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<p>In a patient with cardiac and skeletal myopathy (MFM1; <a href="/entry/601419">601419</a>), <a href="#27" class="mim-tip-reference" title="Park, K.-Y., Dalakas, M. C., Goebel, H. H., Ferrans, V. J., Semino-Mora, C., Litvak, S., Takeda, K., Goldfarb, L. G. <strong>Desmin splice variants causing cardiac and skeletal myopathy.</strong> J. Med. Genet. 37: 851-857, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11073539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11073539</a>] [<a href="https://doi.org/10.1136/jmg.37.11.851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11073539">Park et al. (2000)</a> identified a heterozygous A-to-G change at the +3 position of the splice donor site of intron 3 of the DES gene. Expression studies confirmed that this mutation caused deletion of exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11073539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a large family diagnosed with autosomal dominant limb-girdle muscular dystrophy and cardiomyopathy (<a href="#23" class="mim-tip-reference" title="Messina, D. N., Speer, M. C., Pericak-Vance, M. A., McNally, E. M. <strong>Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23.</strong> Am. J. Hum. Genet. 61: 909-917, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9382102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9382102</a>] [<a href="https://doi.org/10.1086/514896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9382102">Messina et al., 1997</a>), <a href="#10" class="mim-tip-reference" title="Greenberg, S. A., Salajegheh, M., Judge, D. P., Feldman, M. W., Kuncl, R. W., Waldon, Z., Steen, H., Wagner, K. R. <strong>Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics.</strong> Ann. Neurol. 71: 141-145, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275259</a>] [<a href="https://doi.org/10.1002/ana.22649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275259">Greenberg et al. (2012)</a> identified a heterozygous A-to-G transition in intron 3 of the desmin gene. The mutation was found after laser capture microdissection of skeletal muscle and mass spectrometry-based proteomics identified desmin as the major constituent of cytoplasmic inclusions. Initial mapping studies on this family by <a href="#23" class="mim-tip-reference" title="Messina, D. N., Speer, M. C., Pericak-Vance, M. A., McNally, E. M. <strong>Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23.</strong> Am. J. Hum. Genet. 61: 909-917, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9382102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9382102</a>] [<a href="https://doi.org/10.1086/514896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9382102">Messina et al. (1997)</a> had found linkage to chromosome 6q23, and the locus was designated 'LGMD1D.' Subsequent mapping by <a href="#10" class="mim-tip-reference" title="Greenberg, S. A., Salajegheh, M., Judge, D. P., Feldman, M. W., Kuncl, R. W., Waldon, Z., Steen, H., Wagner, K. R. <strong>Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics.</strong> Ann. Neurol. 71: 141-145, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275259</a>] [<a href="https://doi.org/10.1002/ana.22649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275259">Greenberg et al. (2012)</a> excluded 6q23 due to absence of cosegregation of this locus with the phenotype in affected family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22275259+9382102" 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">rs267607484 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607484;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=rs267607484" 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=rs267607484" 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=RCV000056806 OR RCV002265589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056806, RCV002265589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056806...</a>
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<p>In a patient with cardiac and skeletal myopathy (MFM1; <a href="/entry/601419">601419</a>), <a href="#27" class="mim-tip-reference" title="Park, K.-Y., Dalakas, M. C., Goebel, H. H., Ferrans, V. J., Semino-Mora, C., Litvak, S., Takeda, K., Goldfarb, L. G. <strong>Desmin splice variants causing cardiac and skeletal myopathy.</strong> J. Med. Genet. 37: 851-857, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11073539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11073539</a>] [<a href="https://doi.org/10.1136/jmg.37.11.851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11073539">Park et al. (2000)</a> identified a heterozygous G-to-A change at the -1 position of the splice acceptor site of intron 2 of the DES gene. Expression studies confirmed that this mutation caused deletion of exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11073539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 MYOPATHY, MYOFIBRILLAR, 1</strong>
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DES, LEU385PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs57955682 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57955682;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=rs57955682" 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=rs57955682" 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=RCV000056775 OR RCV002265562" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056775, RCV002265562" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056775...</a>
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<p>In a patient with cardiomyopathy and distal weakness (MFM1; <a href="/entry/601419">601419</a>), <a href="#35" class="mim-tip-reference" title="Sugawara, M., Kato, K., Komatsu, M., Wada, C., Kawamura, K., Shindo, S., Yoshioka, N., Tanaka, K., Watanabe, S., Toyoshima, I. <strong>A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates.</strong> Neurology 55: 986-990, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11061256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11061256</a>] [<a href="https://doi.org/10.1212/wnl.55.7.986" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11061256">Sugawara et al. (2000)</a> identified a de novo missense mutation in the DES gene: a C-to-T transition in exon 6, resulting in a leu385-to-pro (L385P) substitution in the C-terminal rod domain. The mutation was not present in the patient's parents or in 100 control subjects. The mutation caused cytoplasmic aggregation and nuclear DNA condensation and fragmentation, suggesting that mutations in this region of desmin may lead to disruption of intermediate filament structure or apoptotic cell death. The authors noted that several other mutations had been found in the C-terminal rod domain and suggested that exon 6 may be a hotspot for mutations causing desmin myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11061256" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<strong>.0011 MYOPATHY, MYOFIBRILLAR, 1</strong>
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DES, GLN389PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913004 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913004;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=rs121913004" 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=rs121913004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056776 OR RCV002265563" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056776, RCV002265563" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056776...</a>
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</span>
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<p>In an isolated case of desmin-related myopathy (MFM1; <a href="/entry/601419">601419</a>), <a href="#9" class="mim-tip-reference" title="Goudeau, B., Dagvadorj, A., Rodrigues-Lima, F., Nedellec, P., Casteras-Simon, M., Perret, E., Langlois, S., Goldfarb, L., Vicart, P. <strong>Structural and functional analysis of a new desmin variant causing desmin-related myopathy.</strong> Hum. Mutat. 18: 388-396, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668632</a>] [<a href="https://doi.org/10.1002/humu.1210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668632">Goudeau et al. (2001)</a> identified a heterozygous 1166A-C transversion in exon 6 of the DES gene, resulting in a gln389-to-pro (Q389P) substitution in the C-terminal part of the desmin rod domain. The patient was a 55-year-old male who had distal muscle weakness since the age of 40 which progressed over the next 10 years to involve proximal muscles as well as velopharyngeal and cardiac muscles. By transfection of desmin cDNA containing the patient's mutation into 3 cell types, <a href="#9" class="mim-tip-reference" title="Goudeau, B., Dagvadorj, A., Rodrigues-Lima, F., Nedellec, P., Casteras-Simon, M., Perret, E., Langlois, S., Goldfarb, L., Vicart, P. <strong>Structural and functional analysis of a new desmin variant causing desmin-related myopathy.</strong> Hum. Mutat. 18: 388-396, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668632</a>] [<a href="https://doi.org/10.1002/humu.1210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668632">Goudeau et al. (2001)</a> demonstrated a dominant-negative effect on desmin filament formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 MYOPATHY, MYOFIBRILLAR, 1</strong>
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DES, GLU359-ALA360-SER361 DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs58409037 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58409037;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=rs58409037" 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=rs58409037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056770 OR RCV002274893" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056770, RCV002274893" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056770...</a>
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<p>In 2 Polish families with myofibrillar myopathy (MFM1; <a href="/entry/601419">601419</a>) without cardiac involvement, <a href="#16" class="mim-tip-reference" title="Kaminska, A., Strelkov, S. V., Goudeau, B., Olive, M., Dagvadorj, A., Fidzianska, A., Simon-Cateras, M., Shatunov, A., Dalakas, M. C., Ferrer, I., Kwiecinski, H., Vicart, P., Goldfarb, L. G. <strong>Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy.</strong> Hum. Genet. 114: 306-313, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14648196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14648196</a>] [<a href="https://doi.org/10.1007/s00439-003-1057-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14648196">Kaminska et al. (2004)</a> found in-frame deletion of 3 amino acids which altered the heptad periodicity within a critical 2B coiled-coil segment. The 3-amino acid deletion introduced a second stutter immediately downstream of the naturally occurring stutter, thus doubling the extent of the local coiled-coil unwinding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14648196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</h4>
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DES, ASN366DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs58687088 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs58687088;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=rs58687088" 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=rs58687088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056771 OR RCV001316353" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056771, RCV001316353" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056771...</a>
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<p>In a Spanish family with cardiac and skeletal myopathy (MFM1; <a href="/entry/601419">601419</a>), <a href="#16" class="mim-tip-reference" title="Kaminska, A., Strelkov, S. V., Goudeau, B., Olive, M., Dagvadorj, A., Fidzianska, A., Simon-Cateras, M., Shatunov, A., Dalakas, M. C., Ferrer, I., Kwiecinski, H., Vicart, P., Goldfarb, L. G. <strong>Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy.</strong> Hum. Genet. 114: 306-313, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14648196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14648196</a>] [<a href="https://doi.org/10.1007/s00439-003-1057-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14648196">Kaminska et al. (2004)</a> found in-frame deletion of a single amino acid residue, asparagine-366. The patient presented with symmetric distal lower limb weakness at the age of 36 years, which progressed to involve the proximal muscles of the legs and arms. He became wheelchair-dependent at the age of 50. He died suddenly at the age of 56 years, probably from cardiac complications. The patient's mother and maternal grandmother suffered from a similar disease and also died suddenly, at the age of 60 and 63 years, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14648196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0014" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0014 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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DES, 3-BP DEL, 720GAA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2125167652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2125167652;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=rs2125167652" 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=rs2125167652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002276892" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002276892" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002276892</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#32" class="mim-tip-reference" title="Schroder, R., Goudeau, B., Simon, M. C., Fischer, D., Eggermann, T., Clemen, C. S., Li, Z., Reimann, J., Xue, Z., Rudnik-Schoneborn, S., Zerres, K., van der Ven, P. F. M., Furst, D. O., Kunz, W. S., Vicart, P. <strong>On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria.</strong> Hum. Molec. Genet. 12: 657-669, 2003. Note: Erratum: Hum. Molec. Genet. 16: 2989-2990, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12620971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12620971</a>] [<a href="https://doi.org/10.1093/hmg/ddg060" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12620971">Schroder et al. (2003)</a> reported a 40-year-old patient with distal myopathy and cardiac arrhythmia (MFM1; <a href="/entry/601419">601419</a>). Patient skeletal muscle fibers showed decreased maximal rates of respiration with glutamate and malate, as well as higher amytal sensitivity, indicating an in vivo inhibition of complex I activity. The patient was found to carry a 3-bp deletion in the DES gene (720_722delGAA) leading to deletion of a single lysine at position 240 (K240del). The K240del mutation was incapable of forming a de novo desmin intermediate filament system in SW13 cells and led to disruption of the endogenous intermediate filament network and formation of pathologic protein aggregates in 3T3 cell. This mutation was reported in an erratum, in which the authors stated that the original genetic analysis was incorrect. The original reported mutation was a 1-bp insertion (5141_5143insA) predicted to lead to a truncated desmin (Lys239fsTer242). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12620971" 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> rs121913005 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913005;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/rs121913005?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=rs121913005" 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=rs121913005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 affected members of a French family with autosomal dominant myofibrillar myopathy-1 (MFM1; <a href="/entry/601419">601419</a>), <a href="#3" class="mim-tip-reference" title="Bar, H., Goudeau, B., Walde, S., Casteras-Simon, M., Mucke, N., Shatunov, A., Goldberg, Y. P., Clarke, C., Holton, J. L., Eymard, B., Katus, H. A., Fardeau, M., Goldfarb, L., Vicart, P., Herrmann, H. <strong>Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies.</strong> Hum. Mutat. 28: 374-386, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17221859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17221859</a>] [<a href="https://doi.org/10.1002/humu.20459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17221859">Bar et al. (2007)</a> identified a 1325C-T transition in the DES gene, resulting in a thr442-to-ile (T442I) substitution in the C-terminal tail domain. The proband had onset of proximal and distal lower limb weakness and dyspnea on exertion at age 35 years, followed by proximal upper limb weakness a year later. He had increased serum creatine kinase and became wheelchair-bound at age 44 years. He underwent tracheostomy for nocturnal ventilatory assistance at age 46 years. A year later he had a pacemaker implanted for bradyarrhythmia. Of note, the patient had repetitive episodes of diarrhea and constipation during the disease course, indicating smooth muscle involvement. His mother and 2 maternal aunts died of heart failure. A sporadic patient from Canada, who also had the mutation, developed distal muscle weakness at age 33 years and cardiomyopathy approximately 5 years later. Functional expression studies in vitro and in cell culture showed that the T442I mutant protein assembled into filaments with abnormal viscometric properties. Coexpression with wildtype desmin showed a severe disturbance of filament formation and filament-filament interaction, indicating an inability for the mutant and wildtype proteins to form mixed filaments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17221859" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0016 SCAPULOPERONEAL SYNDROME, NEUROGENIC, KAESER TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs57965306 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs57965306;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/rs57965306?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=rs57965306" 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=rs57965306" 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=RCV000018329 OR RCV000056767 OR RCV000651542" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018329, RCV000056767, RCV000651542" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018329...</a>
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<p>In the large, multigenerational kindred with scapuloperoneal weakness and atrophy (SCPNK; <a href="/entry/181400">181400</a>) originally described by Kaeser (<a href="#14" class="mim-tip-reference" title="Kaeser, H. E. <strong>Die familiaere scapuloperoneale Muskelatrophie.</strong> Dtsch. Z. Nervenheilk. 186: 379-394, 1964."None>1964</a>, <a href="#15" class="mim-tip-reference" title="Kaeser, H. E. <strong>Scapuloperoneal muscular atrophy.</strong> Brain 88: 407-418, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5828910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5828910</a>] [<a href="https://doi.org/10.1093/brain/88.2.407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5828910">1965</a>), <a href="#42" class="mim-tip-reference" title="Walter, M. C., Reilich, P., Huebner, A., Fischer, D., Schroder, R., Vorgerd, M., Kress, W., Born, C., Schoser, B. G., Krause, K. H., Klutzny, U. Bulst, S. Frey, J. R., Lochmuller, H. <strong>Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.</strong> Brain 130: 1485-1496, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17439987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17439987</a>] [<a href="https://doi.org/10.1093/brain/awm039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17439987">Walter et al. (2007)</a> detected a heterozygous 1049G-C transversion in the DES gene that resulted in an arg350-to-pro (R350P) amino acid substitution in all affected members. This mutation had been described by <a href="#2" class="mim-tip-reference" title="Bar, H., Fischer, D., Goudeau, B., Kley, R. A., Clemen, C. S., Vicart, P., Herrmann, H., Vorgerd, M., Schroeder, R. <strong>Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro.</strong> Hum. Molec. Genet. 14: 1251-1260, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800015</a>] [<a href="https://doi.org/10.1093/hmg/ddi136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800015">Bar et al. (2005)</a> in a family with mixed distal myopathy/limb girdle phenotype, presented as family 4 by <a href="#42" class="mim-tip-reference" title="Walter, M. C., Reilich, P., Huebner, A., Fischer, D., Schroder, R., Vorgerd, M., Kress, W., Born, C., Schoser, B. G., Krause, K. H., Klutzny, U. Bulst, S. Frey, J. R., Lochmuller, H. <strong>Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.</strong> Brain 130: 1485-1496, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17439987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17439987</a>] [<a href="https://doi.org/10.1093/brain/awm039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17439987">Walter et al. (2007)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17439987+5828910+15800015" 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="Bar, H., Fischer, D., Goudeau, B., Kley, R. A., Clemen, C. S., Vicart, P., Herrmann, H., Vorgerd, M., Schroeder, R. <strong>Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro.</strong> Hum. Molec. Genet. 14: 1251-1260, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800015</a>] [<a href="https://doi.org/10.1093/hmg/ddi136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800015">Bar et al. (2005)</a> reported the effects of the R350P mutation, which resides in conserved coil 2B domain of the alpha-helical coiled-coil desmin rod domain. Transfection studies showed that R350P-mutant desmin was incapable of de novo formation of a desmin intermediate filament network in vimentin (<a href="/entry/193060">193060</a>)-free cells, and that it disrupted the endogenous vimentin cytoskeleton in fibroblasts. In vitro studies revealed that the assembly process of R350P-mutant desmin was already disturbed at the unit length filament level, and that further association reactions generated huge, tightly packed protein aggregates. A ratio of 1:3 (R350P to wildtype) was sufficient to effectively block the normal polymerization process of desmin intermediate filaments. <a href="#2" class="mim-tip-reference" title="Bar, H., Fischer, D., Goudeau, B., Kley, R. A., Clemen, C. S., Vicart, P., Herrmann, H., Vorgerd, M., Schroeder, R. <strong>Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro.</strong> Hum. Molec. Genet. 14: 1251-1260, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15800015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15800015</a>] [<a href="https://doi.org/10.1093/hmg/ddi136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15800015">Bar et al. (2005)</a> concluded that the R350P mutation exerted a dominant-negative effect on the ordered lateral arrangement of desmin subunits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15800015" 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">rs62635763 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62635763;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=rs62635763" 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=rs62635763" 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=RCV000056783 OR RCV000817811" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056783, RCV000817811" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056783...</a>
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<p>In 7 affected members of a large Swedish family with autosomal dominant myofibrillary myopathy-1 with arrhythmogenic right ventricular cardiomyopathy (MFM1; <a href="/entry/601419">601419</a>) originally reported by <a href="#22" class="mim-tip-reference" title="Melberg, A., Oldfors, A., Blomstrom-Lundqvist, C., Stalberg, E., Carlsson, B., Larsson, E., Lidell, C., Eeg-Olofsson, K. E., Wikstrom, G., Henriksson, K. G., Dahl, N. <strong>Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q.</strong> Ann. Neurol. 46: 684-692, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10970245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10970245</a>] [<a href="https://doi.org/10.1002/1531-8249(199911)46:5<684::aid-ana2>3.0.co;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10970245">Melberg et al. (1999)</a>, <a href="#11" class="mim-tip-reference" title="Hedberg, C., Melberg, A., Kuhl, A., Jenne, D., Oldfors, A. <strong>Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation.</strong> Europ. J. Hum. Genet. 20: 984-985, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22395865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22395865</a>] [<a href="https://doi.org/10.1038/ejhg.2012.39" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22395865">Hedberg et al. (2012)</a> identified a heterozygous 1255C-T transition in exon 7 of the DES gene, resulting in a pro419-to-ser (P419S) substitution in the tail region of desmin. The mutation was identified by exome sequencing and confirmed by Sanger sequencing. The phenotype in this family was characterized by variable muscle weakness associated with myopathic changes and desmin accumulation on muscle biopsy. Three patients had arrhythmogenic right ventricular cardiomyopathy, resulting in death. Initial mapping studies on this family by <a href="#22" class="mim-tip-reference" title="Melberg, A., Oldfors, A., Blomstrom-Lundqvist, C., Stalberg, E., Carlsson, B., Larsson, E., Lidell, C., Eeg-Olofsson, K. E., Wikstrom, G., Henriksson, K. G., Dahl, N. <strong>Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q.</strong> Ann. Neurol. 46: 684-692, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10970245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10970245</a>] [<a href="https://doi.org/10.1002/1531-8249(199911)46:5<684::aid-ana2>3.0.co;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10970245">Melberg et al. (1999)</a> had found linkage to chromosome 10q22, and the locus was formerly designated in OMIM as ARVD7. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10970245+22395865" 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> rs398122940 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122940;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/rs398122940?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=rs398122940" 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=rs398122940" 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=RCV001781382 OR RCV001814034 OR RCV002265587" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001781382, RCV001814034, RCV002265587" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001781382...</a>
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<p>In 2 Turkish sibs, diagnosed with autosomal recessive limb-girdle muscular dystrophy (LGMD2R), which was reclassified as a form of myofibrillar myopathy (MFM1; <a href="/entry/601419">601419</a>) by <a href="#34" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, <a href="#6" class="mim-tip-reference" title="Cetin, N., Balci-Hayta, B., Gundesli, H., Korkusuz, P., Purali, N., Talim, B., Tan, E., Selcen, D., Erdem-Ozdamar, S., Dincer, P. <strong>A novel desmin mutation leading to autosomal recessive limb-girdle muscular dystrophy: distinct histopathological outcomes compared with desminopathies.</strong> J. Med. Genet. 50: 437-443, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687351</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-101487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687351">Cetin et al. (2013)</a> identified a homozygous A-to-G transition in intron 7 of the DES gene (c.1289-2A-G), resulting in a splice site mutation and the addition of 16 amino acids in the C terminus beginning from residue 428. The parents of the sibs were consanguineous. The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder and was not found in several control databases. The mutant protein was expressed in patient skeletal muscle, which had normal myofibrillar organization, but confocal laser scanning microscopy showed a disruption in binding between desmin and lamin B (LMNB1; <a href="/entry/150340">150340</a>), a component of the nuclear lamina. The patients had onset in their teens or twenties of progressive proximal muscle weakness and atrophy affecting the upper and lower limbs. Neither patient had evidence of a cardiomyopathy, and muscle biopsy showed dystrophic changes without protein aggregates or myofibrillar myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30055862+23687351" 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">rs62636495 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62636495;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=rs62636495" 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=rs62636495" 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=RCV000037240 OR RCV000056801 OR RCV001389153" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000037240, RCV000056801, RCV001389153" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000037240...</a>
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<p>In affected members of 2 distantly related Dutch families segregating autosomal dominant myofibrillar myopathy-1 (MFM1; <a href="/entry/601419">601419</a>) with a highly heterogeneous clinical picture, varying from isolated dilated cardiomyopathy to more generalized skeletal myopathy and mild respiratory problems, <a href="#5" class="mim-tip-reference" title="Bergman, J. E. H., Veenstra-Knol, H. E., van Essen, A. J., van Ravenswaaij, C. M. A., den Dunnen, W. F. A., van den Wijngaard, A., van Tintelen, J. P. <strong>Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.</strong> Europ. J. Med. Genet. 50: 355-366, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17720647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17720647</a>] [<a href="https://doi.org/10.1016/j.ejmg.2007.06.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17720647">Bergman et al. (2007)</a> identified heterozygosity for a c.38C-T transition in exon 1 of the DES gene, resulting in a ser13-to-phe (S13F) substitution within a highly conserved nonapeptide motif in the 'head' domain. The authors noted that the serine at position 13 serves as a phosphorylation site for protein kinase C (<a href="/entry/176960">176960</a>) and is required for appropriate dimer-dimer formation. The mutation was not found in unaffected family members or in 216 ethnically matched controls. Haplotype analysis confirmed the distant relationship between the 2 families, who resided in nearby villages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17720647" 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 39-year-old Chinese man who presented with complete heart block and mild proximal and distal limb weakness, <a href="#29" class="mim-tip-reference" title="Pica, E. C., Kathirvel, P., Pramono, Z. A. D., Lai, P.-S., Yee, W.-C. <strong>Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family.</strong> Neuromusc. Disord. 18: 178-182, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18061454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18061454</a>] [<a href="https://doi.org/10.1016/j.nmd.2007.09.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18061454">Pica et al. (2008)</a> identified heterozygosity for the S13F mutation in the DES gene. His mother and 2 sibs, who were also heterozygous for the mutation, had somewhat milder limb weakness. His affected brother also reported 2 episodes of unexplained syncope, whereas his affected sister reported episodes of palpitations. The mutation was not found in his unaffected father or in 100 unrelated controls. Transfection studies in BHK21 and MCF7 cells demonstrated a fine filamentous desmin network with both mutant and wildtype DES; however, there were significantly more large accumulations of desmin material with the S13F mutant compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18061454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="van Tintelen, J. P., Van Gelder, I. C., Asimaki, A., Suurmeijer, A. J. H., Wiesfeld, A. C. P., Jongbloed, J. D. H., van den Wijngaard, A., Kuks, J. B. M., van Spaendonck-Zwarts, K. Y., Notermans, N., Boven, L., van den Heuvel, F., Veenstra-Knol, H. E., Saffitz, J. E., Hofstra, R. M. W., van den Berg, M. P. <strong>Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene.</strong> Heart Rhythm 6: 1574-1583, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19879535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19879535</a>] [<a href="https://doi.org/10.1016/j.hrthm.2009.07.041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19879535">Van Tintelen et al. (2009)</a> restudied the Dutch kindred with MFM1 reported by <a href="#5" class="mim-tip-reference" title="Bergman, J. E. H., Veenstra-Knol, H. E., van Essen, A. J., van Ravenswaaij, C. M. A., den Dunnen, W. F. A., van den Wijngaard, A., van Tintelen, J. P. <strong>Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.</strong> Europ. J. Med. Genet. 50: 355-366, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17720647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17720647</a>] [<a href="https://doi.org/10.1016/j.ejmg.2007.06.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17720647">Bergman et al. (2007)</a> and expanded it to include 3 distantly related families. The authors described 2 more affected Dutch families whose ancestors could be traced to the same small, poorly populated region in which the common ancestral couple of the large Dutch kindred had lived. All 27 affected individuals were heterozygous for the S13F mutation, which was not found in 300 ethnically matched chromosomes. Based on haplotype analysis, the mutation was estimated to be between 220 and 495 years old. All affected family members demonstrated a fully penetrant yet variable, predominantly cardiologic phenotype, characterized by conduction disease at an early age and right ventricular involvement, including right bundle branch block (RBBB) and/or right ventricular tachycardias and ARVC phenocopies. Immunofluorescence of patient cardiomyocytes showed abnormal intercalated discs with a convoluted and elongated shape in a strong zigzag pattern, compared to the straight, robust lines of high intensity seen in control myocardia. These highly irregular and twisted intercalated discs were also observed on electron microscopy; however, Z discs appeared to be aligned. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17720647+19879535" 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">rs267607482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607482;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=rs267607482" 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=rs267607482" 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=RCV000056764 OR RCV001380949" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056764, RCV001380949" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056764...</a>
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<p>In a Dutch patient with desmin-related myopathy and ARVC (MFM1; <a href="/entry/601419">601419</a>), <a href="#26" class="mim-tip-reference" title="Otten, E., Asimaki, A., Maass, A., van Langen, I. M., van der Wal, A., de Jonge, N., van den Berg, M. P., Saffitz, J. E., Wilde, A. A. M., Jongbloed, J. D. H., van Tintelen, J. P. <strong>Desmin mutations as a cause of right ventricular heart failure affect the intercalated disks.</strong> Heart Rhythm 7: 1058-1064, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20423733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20423733</a>] [<a href="https://doi.org/10.1016/j.hrthm.2010.04.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20423733">Otten et al. (2010)</a> identified heterozygosity for a c.1024A-G transition in exon 6 of the DES gene, resulting in an asn342-to-asp (N342D) substitution at a highly conserved residue. The mutation was present in the patient's similarly affected brother but was not found in 300 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20423733" 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> rs62636492 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62636492;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/rs62636492?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=rs62636492" 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=rs62636492" 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=RCV000037224 OR RCV000056766 OR RCV000157164 OR RCV001039932 OR RCV001250885 OR RCV003298065 OR RCV003398603 OR RCV003486560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000037224, RCV000056766, RCV000157164, RCV001039932, RCV001250885, RCV003298065, RCV003398603, RCV003486560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000037224...</a>
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<p>In a man who was diagnosed with dilated cardiomyopathy (CMD1I; <a href="/entry/604765">604765</a>) at age 55 years, <a href="#37" class="mim-tip-reference" title="Taylor, M. R. G., Slavov, D., Ku, L., Di Lenarda, A., Sinagra, G., Carniel, E., Haubold, K., Boucek, M. M., Ferguson, D., Graw, S. L., Zhu, X., Cavanaugh, J., Sucharov, C. C., Long, C. S., Bristow, M. R., Lavori, P., Maestroni, L., BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank. <strong>Prevalence of desmin mutations in dilated cardiomyopathy.</strong> Circulation 115: 1244-1251, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17325244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17325244</a>] [<a href="https://doi.org/10.1161/CIRCULATIONAHA.106.646778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17325244">Taylor et al. (2007)</a> identified heterozygosity for a c.1134C-T transition in the DES gene, resulting in an arg350-to-trp (R350W) substitution at a residue within the conserved alpha-helical coil of the 2B rod domain. DNA from family members was unavailable for analysis, but the mutation was not found in 300 control chromosomes. The proband, who was negative for mutation in 6 known CMD-associated genes, had no overt skeletal muscle involvement, and creatine kinase level was normal. Immunofluorescence microscopy of transfected SW13 cells, human coronary artery smooth muscle cells, and neonatal rat cardiac myocytes expressing the R350W mutation revealed severe disruption of the normal desmin cytoskeletal architecture in the majority of transfected cells, with clumping and aggregation of antibody-positive staining cytoplasmic protein. The mutation demonstrated a dominant phenotype in the human coronary artery smooth muscle cell lines, in which constitutively expressed desmin was unable to compensate for the presence of the R350W mutant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17325244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1093/hmg/ddi136" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20459" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0504568102" target="_blank">Full Text</a>]
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<strong>Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.</strong>
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[<a href="https://doi.org/10.1016/j.ejmg.2007.06.003" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2012-101487" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM200003163421104" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/1300" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.1210" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.22649" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/mus.880170204" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00354299" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/brain/88.2.407" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s00439-003-1057-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.M704733200" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/bbrc.1993.1138" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.cir.100.5.461" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/dbio.1996.0122" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0378-1119(89)90227-8" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1531-8249(199911)46:5<684::aid-ana2>3.0.co;2-#" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/514896" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1053/euhj.2001.2836" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.95.19.11312" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.hrthm.2010.04.023" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0378-1119(85)90217-3" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/8.12.2191" target="_blank">Full Text</a>]
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Straub, V., Murphy, A., Udd, B.
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<strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055862" 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.nmd.2018.05.007" target="_blank">Full Text</a>]
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Sugawara, M., Kato, K., Komatsu, M., Wada, C., Kawamura, K., Shindo, S., Yoshioka, N., Tanaka, K., Watanabe, S., Toyoshima, I.
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<strong>A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11061256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11061256</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11061256" 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/10.1212/wnl.55.7.986" target="_blank">Full Text</a>]
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Tam, J. L. Y., Triantaphyllopoulos, K., Todd, H., Raguz, S., de Wit, T., Morgan, J. E., Partridge, T. A., Makrinou, E., Grosveld, F., Antoniou, M.
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<strong>The human desmin locus: gene organization and LCR-mediated transcriptional control.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16545539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16545539</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16545539" 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.ygeno.2006.01.009" target="_blank">Full Text</a>]
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Taylor, M. R. G., Slavov, D., Ku, L., Di Lenarda, A., Sinagra, G., Carniel, E., Haubold, K., Boucek, M. M., Ferguson, D., Graw, S. L., Zhu, X., Cavanaugh, J., Sucharov, C. C., Long, C. S., Bristow, M. R., Lavori, P., Maestroni, L., BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17325244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17325244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17325244" 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/10.1161/CIRCULATIONAHA.106.646778" target="_blank">Full Text</a>]
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Tidball, J. G.
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<strong>Desmin at myotendinous junctions.</strong>
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Exp. Cell Res. 199: 206-212, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1544366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1544366</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1544366" 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/10.1016/0014-4827(92)90425-8" target="_blank">Full Text</a>]
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van Tintelen, J. P., Van Gelder, I. C., Asimaki, A., Suurmeijer, A. J. H., Wiesfeld, A. C. P., Jongbloed, J. D. H., van den Wijngaard, A., Kuks, J. B. M., van Spaendonck-Zwarts, K. Y., Notermans, N., Boven, L., van den Heuvel, F., Veenstra-Knol, H. E., Saffitz, J. E., Hofstra, R. M. W., van den Berg, M. P.
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<strong>Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19879535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19879535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19879535" 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.hrthm.2009.07.041" target="_blank">Full Text</a>]
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Vicart, P., Dupret, J.-M., Hazan, J., Li, Z., Gyapay, G., Krishnamoorthy, R., Weissenbach, J., Fardeau, M., Paulin, D.
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<strong>Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy.</strong>
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Hum. Genet. 98: 422-429, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8792816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8792816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8792816" 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/s004390050233" target="_blank">Full Text</a>]
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Viegas-Pequignot, E., Lin, L. Z., Dutrillaux, B., Apiou, F., Paulin, D.
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<strong>Assignment of human desmin gene to band 2q35 by nonradioactive in situ hybridization.</strong>
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Hum. Genet. 83: 33-36, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2670738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2670738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2670738" 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/BF00274143" target="_blank">Full Text</a>]
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<strong>Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.</strong>
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Brain 130: 1485-1496, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17439987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17439987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17439987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awm039" target="_blank">Full Text</a>]
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<strong>Generation of tension by skinned fibers and intact skeletal muscles from desmin-deficient mice.</strong>
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Biochem. Biophys. Res. Commun. 278: 419-425, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11097852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11097852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11097852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/bbrc.2000.3810" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 07/30/2020
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Marla J. F. O'Neill - updated : 8/13/2014<br>Cassandra L. Kniffin - updated : 7/22/2013<br>Cassandra L. Kniffin - updated : 10/23/2012<br>Cassandra L. Kniffin - updated : 4/2/2012<br>Matthew B. Gross - updated : 2/17/2012<br>Patricia A. Hartz - updated : 2/14/2012<br>Marla J. F. O'Neill - updated : 3/12/2010<br>George E. Tiller - updated : 5/30/2008<br>Victor A. McKusick - updated : 2/19/2008<br>Cassandra L. Kniffin - updated : 5/23/2007<br>Patricia A. Hartz - updated : 7/17/2006<br>Patricia A. Hartz - updated : 1/27/2006<br>George E. Tiller - updated : 2/15/2005<br>Patricia A. Hartz - updated : 11/5/2004<br>Patricia A. Hartz - updated : 9/9/2004<br>Cassandra L. Kniffin - reorganized : 7/23/2004<br>Victor A. McKusick - updated : 2/9/2004<br>Patricia A. Hartz - updated : 6/6/2003<br>Kathryn R. Wagner - updated : 2/20/2001<br>Michael J. Wright - updated : 2/13/2001<br>Victor A. McKusick - updated : 8/21/2000<br>Victor A. McKusick - updated : 5/1/2000<br>Carol A. Bocchini - updated : 4/24/2000<br>Victor A. McKusick - updated : 11/19/1999<br>Paul Brennan - updated : 8/31/1999<br>Victor A. McKusick - updated : 10/5/1998<br>Victor A. McKusick - updated : 7/29/1998
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Victor A. McKusick : 6/4/1986
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carol : 07/30/2020<br>carol : 09/26/2018<br>carol : 05/11/2018<br>carol : 02/09/2015<br>mcolton : 2/6/2015<br>mcolton : 2/5/2015<br>mgross : 8/20/2014<br>alopez : 8/19/2014<br>mcolton : 8/13/2014<br>carol : 7/25/2013<br>carol : 7/24/2013<br>ckniffin : 7/22/2013<br>alopez : 12/17/2012<br>carol : 10/24/2012<br>ckniffin : 10/23/2012<br>carol : 4/24/2012<br>carol : 4/4/2012<br>ckniffin : 4/2/2012<br>mgross : 2/17/2012<br>mgross : 2/17/2012<br>terry : 2/14/2012<br>wwang : 3/17/2010<br>terry : 3/12/2010<br>terry : 7/3/2008<br>wwang : 6/3/2008<br>terry : 5/30/2008<br>alopez : 2/22/2008<br>terry : 2/19/2008<br>wwang : 6/12/2007<br>ckniffin : 5/23/2007<br>mgross : 8/7/2006<br>mgross : 8/7/2006<br>terry : 7/17/2006<br>mgross : 2/1/2006<br>terry : 1/27/2006<br>carol : 8/29/2005<br>alopez : 7/20/2005<br>terry : 3/16/2005<br>terry : 3/11/2005<br>wwang : 2/21/2005<br>terry : 2/15/2005<br>mgross : 11/9/2004<br>terry : 11/5/2004<br>mgross : 9/9/2004<br>carol : 7/23/2004<br>ckniffin : 7/22/2004<br>ckniffin : 7/22/2004<br>cwells : 2/19/2004<br>terry : 2/9/2004<br>tkritzer : 2/6/2004<br>mgross : 6/6/2003<br>carol : 1/15/2002<br>mcapotos : 12/11/2001<br>terry : 11/29/2001<br>carol : 3/29/2001<br>mcapotos : 3/26/2001<br>carol : 2/20/2001<br>alopez : 2/13/2001<br>mcapotos : 9/8/2000<br>mcapotos : 9/6/2000<br>terry : 8/21/2000<br>mcapotos : 5/31/2000<br>mcapotos : 5/26/2000<br>mcapotos : 5/24/2000<br>terry : 5/1/2000<br>carol : 4/24/2000<br>mgross : 3/30/2000<br>carol : 3/30/2000<br>mgross : 1/24/2000<br>carol : 12/6/1999<br>alopez : 12/2/1999<br>terry : 11/19/1999<br>carol : 10/20/1999<br>mgross : 9/13/1999<br>mgross : 9/10/1999<br>mgross : 8/31/1999<br>dkim : 10/13/1998<br>carol : 10/9/1998<br>terry : 10/5/1998<br>alopez : 7/31/1998<br>alopez : 7/30/1998<br>alopez : 7/30/1998<br>terry : 7/29/1998<br>alopez : 7/7/1997<br>terry : 9/12/1996<br>mark : 7/3/1996<br>terry : 7/3/1996<br>terry : 6/21/1996<br>mark : 6/20/1996<br>joanna : 12/4/1995<br>joanna : 12/4/1995<br>joanna : 12/3/1995<br>carol : 8/30/1993<br>carol : 8/18/1993<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>root : 10/9/1989
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<h3>
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<span class="mim-font">
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<strong>*</strong> 125660
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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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DESMIN; DES
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</span>
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</h3>
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</div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: DES</em></strong>
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</span>
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</p>
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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> 1208615009, 770627003;
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</p>
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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: 2q35
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:219,418,377-219,426,734 </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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2q35
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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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Cardiomyopathy, dilated, 1I
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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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604765
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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Myopathy, myofibrillar, 1
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</span>
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</td>
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<span class="mim-font">
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601419
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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; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<td>
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<span class="mim-font">
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Scapuloperoneal syndrome, neurogenic, Kaeser type
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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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181400
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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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</td>
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</tr>
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</tbody>
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</table>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Desmin is the muscle-specific member of the intermediate filament (IF) protein family. It is one of the earliest myogenic markers, both in heart and somites, and is expressed in satellite stem cells and replicating myoblasts. In mature striated muscle, desmin IFs form a 3-dimensional scaffold that appears to extend across the diameter of the myofibril. Desmin IFs surround the Z discs and link the entire contractile apparatus to the sarcolemmal cytoskeleton, cytoplasmic organelles, and nucleus (summary by Kouloumenta et al., 2007). </p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Li et al. (1989) determined that the DES gene encodes a 468-amino acid protein that shares structural features with other intermediate filament proteins, including helical domains, a stretch of heptad repeats, and the positions of linkers. Northern blot analysis detected a 2.2-kb transcript in striated skeletal muscle, uterine smooth muscle, and cultured striated muscle cells. </p><p>From a human muscle biopsy, Vicart et al. (1996) cloned and sequenced the DES gene, which encodes a 469-amino acid protein with a molecular mass of 53 kD. The head domain of desmin, comprising residues 1 to 82, has several putative phosphorylation sites, and the rod domain, comprising residues 83 to 423, contains primarily conserved hydrophobic amino acids. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene 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>Tidball (1992) found that desmin was codistributed with actin thin filaments within the cellular processes of myotendinous junctions in frog skeletal muscle. Desmin appeared to mediate attachments between the terminal Z disc and the junctional membrane, as well as linking Z discs in series in each sarcomere. In contrast to other cytoskeletal proteins, desmin was located deep in the cellular processes within the filamentous core 30 nm or more from the membrane. Tidball (1992) concluded that desmin provides attachments between the terminal Z disc and membrane-associated proteins to form a force-transmitting system that parallels the thin filaments at myotendinous junctions. </p><p>Kusubata et al. (1993) found that serine/threonine phosphorylation in the head domain of chicken desmin by Cdc2 kinase (116940) induced a transition toward the depolymerization of desmin filaments. </p><p>By yeast 2-hybrid analysis of a human heart cDNA library, Kouloumenta et al. (2007) found that the N-terminal domain of mouse desmin interacted with the C terminus of human myospryn (CMYA5; 612193). Reciprocal coimmunoprecipitation experiments and protein pull-down assays with in vitro-translated proteins confirmed direct interaction. Deletion analysis revealed that desmin bound the C-terminal SPRY domain of myospryn. Confocal microscopy of cultured unfused primary mouse cardiomyocytes revealed that the 2 proteins colocalized in a punctate pattern at the nuclear periphery. Western blot analysis of immunoprecipitates of adult mouse heart showed that desmin associated with the lysosome biogenesis complex components dysbindin and pallidin, possibly via its interaction with myospryn. In adult mouse hearts, desmin and myospryn colocalized at intercalated discs. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Li et al. (1989) determined that the DES gene contains 9 exons and spans about 8.4 kb. Intronic sequences contain 4 AluI repetitive elements, and the promoter region is G rich. </p><p>Locus control regions (LCRs) are transcriptional regulatory elements, like CpG islands, that establish a transcriptionally competent open chromatin structure. Unlike CpG islands, LCRs have invariably been found linked with tissue-specific genes. Tam et al. (2006) identified a muscle-specific LCR linked to the DES gene. The DES LCR is a complex multicomponent element located within 18 kb 5-prime of the DES transcriptional start site. Tam et al. (2006) identified 2 genes immediately downstream of DES, SPEG and APEG1 (see 615950), that are also preferentially expressed in muscle, and they suggested that the DES LCR may form a functional expression module involved in regulating expression of all 3 genes. </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>By use of cDNA clones of desmin in somatic cell hybrids, Quax et al. (1985) assigned the DES gene to chromosome 2. By in situ hybridization, Viegas-Pequignot et al. (1989) localized the gene to 2q35. </p><p>In the mouse, Jankowski and Gumucio (1995) demonstrated that the genes for tensin (600076), villin (193040), and desmin are closely linked on chromosome 1. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Myofibrillar Myopathy 1</em></strong></p><p>
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Goldfarb et al. (1998) reported 2 families with desmin-related cardioskeletal myopathy (MFM1; 601419) associated with mutations in the highly conserved C-terminal portion of the desmin rod domain. A heterozygous (125660.0001) mutation was found in a family with an adult-onset skeletal myopathy and mild cardiac involvement. Compound heterozygosity for 2 other desmin mutations (125660.0002; 125660.0003) was detected in a second family with a childhood-onset aggressive course of cardiac and skeletal myopathy. </p><p>Dalakas et al. (2000) searched for mutations in the desmin gene in 22 patients from 8 families with dominantly inherited myofibrillar or desmin-related myopathy and 2 patients with sporadic disease. They identified mutations in 12 patients (10 from 4 families and 2 sporadic), 7 of whom had cardiomyopathy. </p><p>Kaminska et al. (2004) studied 3 families with skeletal or cardioskeletal myopathy caused by small in-frame deletions in the desmin gene. Two Polish families with skeletal myopathy without cardiac involvement had an in-frame deletion of 3 amino acids (125660.0012) in an area known to be conserved in evolution. An affected Spanish family had a single amino acid deletion (125660.0013). Kaminska et al. (2004) showed that these small deletions disturbed the coiled-coil structure of desmin in a highly specific way. </p><p>In 4 unrelated probands with desmin-related myopathy, Bar et al. (2007) identified 3 novel mutations in the DES gene (see, e.g., 125660.0015) located in the non-alpha-helical C-terminal tail domain of the protein. All had severe skeletal and cardiac muscle involvement. Functional expression studies of these and other tail domain pathogenic mutations revealed that different mutations in the tail region had different functional effects. Although some mutant proteins were unable to assemble into filaments, most formed filaments with altered viscometric properties and/or impaired ability to assemble properly with wildtype desmin. Bar et al. (2007) suggested that desmin tail mutations can affect multiple pathways, including mechanochemical signaling, intracellular transport, and interactions with other proteins, resulting in distinct cellular malfunctions and variable clinical phenotypes. </p><p>In affected members of 2 distantly related Dutch families segregating autosomal dominant desmin-related myopathy with a highly heterogeneous clinical picture, varying from isolated dilated cardiomyopathy to more generalized skeletal myopathy and mild respiratory problems, Bergman et al. (2007) identified heterozygosity for a missense mutation in the DES gene (S13F; 125660.0019) that was not present in unaffected family members. </p><p>In 4 affected members of a 2-generation Chinese family with desmin-related myopathy, Pica et al. (2008) identified heterozygosity for the S13F mutation in the DES gene. </p><p>Van Tintelen et al. (2009) restudied the Dutch kindred with MFM1 reported by Bergman et al. (2007) and expanded it to include 3 distantly related families. The authors described 2 more affected Dutch families whose ancestors could be traced to the same small, poorly populated region in which the common ancestral couple of the large Dutch kindred had lived. All 27 affected individuals were heterozygous for the DES S13F mutation; based on haplotype analysis, the mutation was estimated to be between 220 and 495 years old. Immunofluorescence analysis of patient myocardia showed normal amounts of the major desmosomal proteins, but intercalated discs were more convoluted and elongated and had a zigzag appearance compared to controls. </p><p>Pinol-Ripoll et al. (2009) reported a female patient with recurrent episodes of syncope from infancy and an aggressive course leading to the devastation of cardiac, skeletal, and smooth musculature and death from cardiac failure at age 20 years, in whom they identified homozygosity for a 21-bp deletion in the desmin gene (125660.0004). Pinol-Ripoll et al. (2009) stated that this was the first reported case of infantile-onset desmin-associated cardiopathy, and noted that their patient had the same mutation previously identified by Munoz-Marmol et al. (1998) in a 15-year-old boy. </p><p>In a Dutch patient with desmin-related myopathy and arrhythmogenic right ventricular cardiomyopathy (ARVC), Otten et al. (2010) identified heterozygosity for a missense mutation in the DES gene (N342D; 125660.0020). </p><p>In affected members of a large Swedish family segregating autosomal dominant MFM1 and ARVC, Hedberg et al. (2012) identified a heterozygous P419S mutation (125660.0017) in the DES gene. </p><p>In 2 Turkish sibs, born of consanguineous parents, with what the authors called autosomal recessive limb-girdle muscular dystrophy (LGMD2R), Cetin et al. (2013) identified a homozygous splice site mutation in the DES gene (125660.0018). LGMD2R was later reclassified as a form of myofibrillar myopathy by Straub et al. (2018). The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder and was not found in several control databases. The mutant protein was expressed in patient skeletal muscle, which had normal myofibrillar organization, but confocal laser scanning microscopy showed a disruption in binding between desmin and lamin B (LMNB1; 150340). The patients had onset in their teens or twenties of progressive proximal muscle weakness and atrophy affecting the upper and lower limbs. Neither patient had evidence of a cardiomyopathy, and muscle biopsy showed dystrophic changes without protein aggregates or myofibrillar myopathy. </p><p><strong><em>Dilated Cardiomyopathy 1I</em></strong></p><p>
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Li et al. (1999) used a candidate gene approach to identify genetic defects in 44 unrelated probands with autosomal dominant dilated cardiomyopathy. In 1 family with pure cardiomyopathy without skeletal myopathy (CMD1I; 604765), they identified a heterozygous ile451-to-met mutation in the DES gene (125660.0005). The reports of Goldfarb et al. (1998) and Li et al. (1999) suggested a distinct cardiac genotype-phenotype correlation for mutations in the DES gene. </p><p>Miyamoto et al. (2001) screened exon 8 of the DES gene in a cohort of 265 Japanese probands with dilated cardiomyopathy and identified 3 unrelated men who were heterozygous for the previously reported I451M mutation. None of the 3 patients showed any clinical evidence of skeletal muscle involvement on physical examination, and none had abnormal serum levels of creatine kinase or a myopathic pattern on electromyelogram. </p><p>Taylor et al. (2007) analyzed the DES gene in 425 probands with dilated cardiomyopathy and identified 5 missense mutations in 6 sporadic patients, 3 of which were likely pathogenic (see, e.g., 125660.0021). None of the patients had overt skeletal muscle involvement, although none had a skeletal muscle biopsy and formal neurologic assessment was not performed in most patients. Functional analysis of the 3 likely pathogenic mutations demonstrated severe disruption of desmin filament assembly. </p><p><strong><em>Neurogenic Scapuloperoneal Syndrome, Kaeser Type</em></strong></p><p>
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In a large, multigenerational kindred with scapuloperoneal weakness and atrophy (SCPNK; 181400) originally described by Kaeser (1964, 1965), Walter et al. (2007) detected a heterozygous missense mutation (125660.0016) in the DES gene in all affected members. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wieneke et al. (2000) generated Des-null mice and found that desmin is not essential for acute tensile strength, but rather for optimal activation of intact myofibers during excitation-contraction coupling. </p><p>Li et al. (1996) developed desmin-null mice. Despite the complete lack of desmin, mutant mice developed and reproduced. Skeletal, cardiac, and smooth muscle formed in mutant mice, but morphologic abnormalities were observed in the diaphragm of adult mice. These abnormalities were characterized by disorganized, distended, and nonaligned fibers. The hearts of mutant mice presented areas of hemorrhage in which fibrosis and ischemia were observed. The absence of desmin also produced defects in smooth muscles. Li et al. (1996) concluded that desmin is not required for myogenic commitment or for myoblast fusion and differentiation of skeletal, cardiac, and smooth muscle, but it is essential to strengthen and maintain the integrity of these tissues. </p><p>Using analytical ultracentrifugation, viscometry, and time-lapse electron microscopy, Bar et al. (2005) examined how myopathy-associated mutations within the alpha-helical rod domain of mouse desmin affected distinct phases of intermediate filament assembly. Whereas 6 of the 14 mutants allowed assembly of desmin into normal filaments in vitro, the other mutants interfered with the assembly process at distinct stages, i.e., tetramer formation, unit-length filament formation, filament elongation, and intermediate filament maturation. Mutants with in vitro assembly defects yielded dot-like aggregates in transfected cells, whereas mutants that formed filaments in vitro formed seemingly normal cytoskeletal intermediate filaments following transfection into vimentin (193060)-free human adrenocortical carcinoma cells or vimentin-positive mouse fibroblasts. Bar et al. (2005) concluded that the degree of assembly defect of a mutant desmin variant in vitro does not correlate directly with disease phenotype. </p><p>By immunohistochemical analysis of wildtype and Des -/- mouse hearts, Kouloumenta et al. (2007) found that Des knockout resulted in abnormalities at the intercalated discs. In primary mouse cardiomyocytes, Des knockout resulted in mislocalization of lysosomes. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>21 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 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DES, ALA337PRO
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<br />
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SNP: rs59962885,
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gnomAD: rs59962885,
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ClinVar: RCV000056762, RCV000856836, RCV002265557
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with adult-onset myofibrillar myopathy-1 (MFM1; 601419) and mild cardiac involvement, Goldfarb et al. (1998) identified a heterozygous G-to-C transversion in exon 5 of the DES gene, resulting in an ala337-to-pro (A337P) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DES, ALA360PRO
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<br />
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SNP: rs121913000,
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ClinVar: RCV002265558
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 of 4 sibs affected with a severe childhood-onset form of cardioskeletal myopathy (MFM1; 601419), Goldfarb et al. (1998) identified compound heterozygosity for 2 mutations in the DES gene: a G-to-C transversion in exon 6, resulting in an ala360-to-pro (A360P) substitution, and an A-to-T transversion in exon 6, resulting in an asn393-to-ile (N393I) substitution (125660.0003). Several older unaffected members of the family who were beyond the maximal age of disease onset had 1 of these mutations; the 55-year-old mother of the affected sibs and her 54-year-old sister showed the A360P mutation, and a 66-year-old paternal uncle carried the N393I mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0003 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DES, ASN393ILE
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<br />
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|
|
SNP: rs121913001,
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|
|
|
gnomAD: rs121913001,
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|
|
ClinVar: RCV000056778, RCV002265559, RCV003162255
|
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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>For discussion of the asn393-to-ile (N393I) mutation in the DES gene that was found in compound heterozygous state in patients with severe childhood-onset myofibrillar myopathy-1 (MFM1; 601419) by Goldfarb et al. (1998), see 125660.0002. </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>.0004 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
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</span>
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</h4>
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</div>
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<div>
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|
<span class="mim-text-font">
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|
DES, 21-BP DEL
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<br />
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|
SNP: rs60538473,
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|
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ClinVar: RCV000056803, RCV002265560
|
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|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a patient with severe generalized myopathy (MFM1; 601419) reported by Ariza et al. (1995), Munoz-Marmol et al. (1998) identified a homozygous 21-bp deletion in the DES gene, predicting a mutant desmin protein lacking 7 amino acids, residues arg173 to glu179. Munoz-Marmol et al. (1998) provided functional analysis to demonstrate that this mutation severely compromised the ability of desmin to assemble into intermediate filaments in vivo and in vitro. In desmin-null mice, myofibrils are fragile upon mechanical stress, and muscle weakness develops with age. This mechanical-sensitive aspect of the phenotype was evident in the patient, who developed muscle weakness in his teens. </p><p>In a female patient who had recurrent episodes of syncope from infancy and an aggressive course leading to the devastation of cardiac, skeletal, and smooth musculature and death from cardiac failure at age 20 years, Pinol-Ripoll et al. (2009) identified homozygosity for the same 21-bp deletion in the DES gene. Her consanguineous unaffected parents were each heterozygous for the mutation. Pinol-Ripoll et al. (2009) stated that this was the youngest known molecularly identified patient with desminopathy. </p>
|
|
</span>
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</div>
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<div>
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|
<br />
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</div>
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</div>
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|
<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CARDIOMYOPATHY, DILATED, 1I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
DES, ILE451MET
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<br />
|
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|
|
SNP: rs121913002,
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|
|
gnomAD: rs121913002,
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|
|
ClinVar: RCV000018318, RCV000056787, RCV000698481, RCV002265561, RCV004018640
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal dominant pure dilated cardiomyopathy (CMD1I; 604765), Li et al. (1999) identified a heterozygous C-to-G transversion at nucleotide 1353 of the DES gene, resulting in an ile451-to-met substitution. This mutation was not present in 920 control chromosomes. The residue involved is located in the carboxy tail domain of the protein, suggesting an important functional role for this region in cardiac myocytes. </p><p>Miyamoto et al. (2001) screened exon 8 of the DES gene in a cohort of 265 Japanese probands with dilated cardiomyopathy and identified 3 unrelated men who were heterozygous for the I451M substitution. None of the 3 patients showed any clinical evidence of skeletal muscle involvement on physical examination, and none had abnormal levels of creatine kinase or a myopathic pattern on electromyelogram. All 3 cases were sporadic; in the 1 family in which parental DNA was available, the mutation was shown to have arisen de novo. Haplotype analysis indicated that 2 of the men might have been ancestrally related. </p>
|
|
</span>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, LEU345PRO
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|
<br />
|
|
|
|
SNP: rs57639980,
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|
|
|
|
|
|
|
ClinVar: RCV000056765, RCV001044194
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large, 6-generation Ashkenazi Jewish family with desmin-related myopathy (MFM1; 601419) reported by Horowitz and Schmalbruch (1994), Sjoberg et al. (1999) identified what they claimed to be the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The leu345-to-pro mutation (L345P) in this kindred was located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin was incapable of forming filamentous networks in transfected HeLa and SW13 cells. Sjoberg et al. (1999) concluded that the L345P mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, ARG406TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913003,
|
|
|
|
|
|
|
|
ClinVar: RCV000056781, RCV000627795, RCV001787806, RCV001798009
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of cardiac and skeletal myopathy (MFM1; 601419), Park et al. (2000) demonstrated heterozygosity for an arg406-to-trp (R406W) mutation in the DES gene. The mutation was not found in the patient's father, mother, or sister. Alternative paternity was excluded. Haplotype analysis indicated that the patient's father was a germline mosaic for the desmin mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, IVS3DS, A-G, +3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607483,
|
|
|
|
|
|
|
|
ClinVar: RCV000056810, RCV000154574, RCV001233592, RCV002381361
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with cardiac and skeletal myopathy (MFM1; 601419), Park et al. (2000) identified a heterozygous A-to-G change at the +3 position of the splice donor site of intron 3 of the DES gene. Expression studies confirmed that this mutation caused deletion of exon 3. </p><p>In affected members of a large family diagnosed with autosomal dominant limb-girdle muscular dystrophy and cardiomyopathy (Messina et al., 1997), Greenberg et al. (2012) identified a heterozygous A-to-G transition in intron 3 of the desmin gene. The mutation was found after laser capture microdissection of skeletal muscle and mass spectrometry-based proteomics identified desmin as the major constituent of cytoplasmic inclusions. Initial mapping studies on this family by Messina et al. (1997) had found linkage to chromosome 6q23, and the locus was designated 'LGMD1D.' Subsequent mapping by Greenberg et al. (2012) excluded 6q23 due to absence of cosegregation of this locus with the phenotype in affected family members. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, IVS2, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607484,
|
|
|
|
|
|
|
|
ClinVar: RCV000056806, RCV002265589
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with cardiac and skeletal myopathy (MFM1; 601419), Park et al. (2000) identified a heterozygous G-to-A change at the -1 position of the splice acceptor site of intron 2 of the DES gene. Expression studies confirmed that this mutation caused deletion of exon 3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, LEU385PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs57955682,
|
|
|
|
|
|
|
|
ClinVar: RCV000056775, RCV002265562
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with cardiomyopathy and distal weakness (MFM1; 601419), Sugawara et al. (2000) identified a de novo missense mutation in the DES gene: a C-to-T transition in exon 6, resulting in a leu385-to-pro (L385P) substitution in the C-terminal rod domain. The mutation was not present in the patient's parents or in 100 control subjects. The mutation caused cytoplasmic aggregation and nuclear DNA condensation and fragmentation, suggesting that mutations in this region of desmin may lead to disruption of intermediate filament structure or apoptotic cell death. The authors noted that several other mutations had been found in the C-terminal rod domain and suggested that exon 6 may be a hotspot for mutations causing desmin myopathy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, GLN389PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913004,
|
|
|
|
|
|
|
|
ClinVar: RCV000056776, RCV002265563
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an isolated case of desmin-related myopathy (MFM1; 601419), Goudeau et al. (2001) identified a heterozygous 1166A-C transversion in exon 6 of the DES gene, resulting in a gln389-to-pro (Q389P) substitution in the C-terminal part of the desmin rod domain. The patient was a 55-year-old male who had distal muscle weakness since the age of 40 which progressed over the next 10 years to involve proximal muscles as well as velopharyngeal and cardiac muscles. By transfection of desmin cDNA containing the patient's mutation into 3 cell types, Goudeau et al. (2001) demonstrated a dominant-negative effect on desmin filament formation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, GLU359-ALA360-SER361 DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs58409037,
|
|
|
|
|
|
|
|
ClinVar: RCV000056770, RCV002274893
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Polish families with myofibrillar myopathy (MFM1; 601419) without cardiac involvement, Kaminska et al. (2004) found in-frame deletion of 3 amino acids which altered the heptad periodicity within a critical 2B coiled-coil segment. The 3-amino acid deletion introduced a second stutter immediately downstream of the naturally occurring stutter, thus doubling the extent of the local coiled-coil unwinding. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, ASN366DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs58687088,
|
|
|
|
|
|
|
|
ClinVar: RCV000056771, RCV001316353
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Spanish family with cardiac and skeletal myopathy (MFM1; 601419), Kaminska et al. (2004) found in-frame deletion of a single amino acid residue, asparagine-366. The patient presented with symmetric distal lower limb weakness at the age of 36 years, which progressed to involve the proximal muscles of the legs and arms. He became wheelchair-dependent at the age of 50. He died suddenly at the age of 56 years, probably from cardiac complications. The patient's mother and maternal grandmother suffered from a similar disease and also died suddenly, at the age of 60 and 63 years, respectively. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DES, 3-BP DEL, 720GAA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2125167652,
|
|
|
|
|
|
|
|
ClinVar: RCV002276892
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Schroder et al. (2003) reported a 40-year-old patient with distal myopathy and cardiac arrhythmia (MFM1; 601419). Patient skeletal muscle fibers showed decreased maximal rates of respiration with glutamate and malate, as well as higher amytal sensitivity, indicating an in vivo inhibition of complex I activity. The patient was found to carry a 3-bp deletion in the DES gene (720_722delGAA) leading to deletion of a single lysine at position 240 (K240del). The K240del mutation was incapable of forming a de novo desmin intermediate filament system in SW13 cells and led to disruption of the endogenous intermediate filament network and formation of pathologic protein aggregates in 3T3 cell. This mutation was reported in an erratum, in which the authors stated that the original genetic analysis was incorrect. The original reported mutation was a 1-bp insertion (5141_5143insA) predicted to lead to a truncated desmin (Lys239fsTer242). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
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DES, THR442ILE
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<br />
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SNP: rs121913005,
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gnomAD: rs121913005,
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ClinVar: RCV000056784, RCV000811753
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected members of a French family with autosomal dominant myofibrillar myopathy-1 (MFM1; 601419), Bar et al. (2007) identified a 1325C-T transition in the DES gene, resulting in a thr442-to-ile (T442I) substitution in the C-terminal tail domain. The proband had onset of proximal and distal lower limb weakness and dyspnea on exertion at age 35 years, followed by proximal upper limb weakness a year later. He had increased serum creatine kinase and became wheelchair-bound at age 44 years. He underwent tracheostomy for nocturnal ventilatory assistance at age 46 years. A year later he had a pacemaker implanted for bradyarrhythmia. Of note, the patient had repetitive episodes of diarrhea and constipation during the disease course, indicating smooth muscle involvement. His mother and 2 maternal aunts died of heart failure. A sporadic patient from Canada, who also had the mutation, developed distal muscle weakness at age 33 years and cardiomyopathy approximately 5 years later. Functional expression studies in vitro and in cell culture showed that the T442I mutant protein assembled into filaments with abnormal viscometric properties. Coexpression with wildtype desmin showed a severe disturbance of filament formation and filament-filament interaction, indicating an inability for the mutant and wildtype proteins to form mixed filaments. </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>.0016 SCAPULOPERONEAL SYNDROME, NEUROGENIC, KAESER TYPE</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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DES, ARG350PRO
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<br />
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SNP: rs57965306,
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gnomAD: rs57965306,
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ClinVar: RCV000018329, RCV000056767, RCV000651542
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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 the large, multigenerational kindred with scapuloperoneal weakness and atrophy (SCPNK; 181400) originally described by Kaeser (1964, 1965), Walter et al. (2007) detected a heterozygous 1049G-C transversion in the DES gene that resulted in an arg350-to-pro (R350P) amino acid substitution in all affected members. This mutation had been described by Bar et al. (2005) in a family with mixed distal myopathy/limb girdle phenotype, presented as family 4 by Walter et al. (2007). </p><p>Bar et al. (2005) reported the effects of the R350P mutation, which resides in conserved coil 2B domain of the alpha-helical coiled-coil desmin rod domain. Transfection studies showed that R350P-mutant desmin was incapable of de novo formation of a desmin intermediate filament network in vimentin (193060)-free cells, and that it disrupted the endogenous vimentin cytoskeleton in fibroblasts. In vitro studies revealed that the assembly process of R350P-mutant desmin was already disturbed at the unit length filament level, and that further association reactions generated huge, tightly packed protein aggregates. A ratio of 1:3 (R350P to wildtype) was sufficient to effectively block the normal polymerization process of desmin intermediate filaments. Bar et al. (2005) concluded that the R350P mutation exerted a dominant-negative effect on the ordered lateral arrangement of desmin subunits. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0017 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DES, PRO419SER
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<br />
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SNP: rs62635763,
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ClinVar: RCV000056783, RCV000817811
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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 7 affected members of a large Swedish family with autosomal dominant myofibrillary myopathy-1 with arrhythmogenic right ventricular cardiomyopathy (MFM1; 601419) originally reported by Melberg et al. (1999), Hedberg et al. (2012) identified a heterozygous 1255C-T transition in exon 7 of the DES gene, resulting in a pro419-to-ser (P419S) substitution in the tail region of desmin. The mutation was identified by exome sequencing and confirmed by Sanger sequencing. The phenotype in this family was characterized by variable muscle weakness associated with myopathic changes and desmin accumulation on muscle biopsy. Three patients had arrhythmogenic right ventricular cardiomyopathy, resulting in death. Initial mapping studies on this family by Melberg et al. (1999) had found linkage to chromosome 10q22, and the locus was formerly designated in OMIM as ARVD7. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0018 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DES, IVS7AS, A-G, -2
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<br />
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SNP: rs398122940,
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gnomAD: rs398122940,
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ClinVar: RCV001781382, RCV001814034, RCV002265587
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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 Turkish sibs, diagnosed with autosomal recessive limb-girdle muscular dystrophy (LGMD2R), which was reclassified as a form of myofibrillar myopathy (MFM1; 601419) by Straub et al. (2018), Cetin et al. (2013) identified a homozygous A-to-G transition in intron 7 of the DES gene (c.1289-2A-G), resulting in a splice site mutation and the addition of 16 amino acids in the C terminus beginning from residue 428. The parents of the sibs were consanguineous. The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder and was not found in several control databases. The mutant protein was expressed in patient skeletal muscle, which had normal myofibrillar organization, but confocal laser scanning microscopy showed a disruption in binding between desmin and lamin B (LMNB1; 150340), a component of the nuclear lamina. The patients had onset in their teens or twenties of progressive proximal muscle weakness and atrophy affecting the upper and lower limbs. Neither patient had evidence of a cardiomyopathy, and muscle biopsy showed dystrophic changes without protein aggregates or myofibrillar myopathy. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0019 MYOPATHY, MYOFIBRILLAR, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DES, SER13PHE
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<br />
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SNP: rs62636495,
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ClinVar: RCV000037240, RCV000056801, RCV001389153
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of 2 distantly related Dutch families segregating autosomal dominant myofibrillar myopathy-1 (MFM1; 601419) with a highly heterogeneous clinical picture, varying from isolated dilated cardiomyopathy to more generalized skeletal myopathy and mild respiratory problems, Bergman et al. (2007) identified heterozygosity for a c.38C-T transition in exon 1 of the DES gene, resulting in a ser13-to-phe (S13F) substitution within a highly conserved nonapeptide motif in the 'head' domain. The authors noted that the serine at position 13 serves as a phosphorylation site for protein kinase C (176960) and is required for appropriate dimer-dimer formation. The mutation was not found in unaffected family members or in 216 ethnically matched controls. Haplotype analysis confirmed the distant relationship between the 2 families, who resided in nearby villages. </p><p>In a 39-year-old Chinese man who presented with complete heart block and mild proximal and distal limb weakness, Pica et al. (2008) identified heterozygosity for the S13F mutation in the DES gene. His mother and 2 sibs, who were also heterozygous for the mutation, had somewhat milder limb weakness. His affected brother also reported 2 episodes of unexplained syncope, whereas his affected sister reported episodes of palpitations. The mutation was not found in his unaffected father or in 100 unrelated controls. Transfection studies in BHK21 and MCF7 cells demonstrated a fine filamentous desmin network with both mutant and wildtype DES; however, there were significantly more large accumulations of desmin material with the S13F mutant compared to wildtype. </p><p>Van Tintelen et al. (2009) restudied the Dutch kindred with MFM1 reported by Bergman et al. (2007) and expanded it to include 3 distantly related families. The authors described 2 more affected Dutch families whose ancestors could be traced to the same small, poorly populated region in which the common ancestral couple of the large Dutch kindred had lived. All 27 affected individuals were heterozygous for the S13F mutation, which was not found in 300 ethnically matched chromosomes. Based on haplotype analysis, the mutation was estimated to be between 220 and 495 years old. All affected family members demonstrated a fully penetrant yet variable, predominantly cardiologic phenotype, characterized by conduction disease at an early age and right ventricular involvement, including right bundle branch block (RBBB) and/or right ventricular tachycardias and ARVC phenocopies. Immunofluorescence of patient cardiomyocytes showed abnormal intercalated discs with a convoluted and elongated shape in a strong zigzag pattern, compared to the straight, robust lines of high intensity seen in control myocardia. These highly irregular and twisted intercalated discs were also observed on electron microscopy; however, Z discs appeared to be aligned. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0020 MYOPATHY, MYOFIBRILLAR, 1</strong>
|
|
</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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DES, ASN342ASP
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<br />
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SNP: rs267607482,
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ClinVar: RCV000056764, RCV001380949
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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 Dutch patient with desmin-related myopathy and ARVC (MFM1; 601419), Otten et al. (2010) identified heterozygosity for a c.1024A-G transition in exon 6 of the DES gene, resulting in an asn342-to-asp (N342D) substitution at a highly conserved residue. The mutation was present in the patient's similarly affected brother but was not found in 300 control chromosomes. </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>.0021 CARDIOMYOPATHY, DILATED, 1I</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
DES, ARG350TRP
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|
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<br />
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|
|
SNP: rs62636492,
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|
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|
|
|
gnomAD: rs62636492,
|
|
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|
|
|
ClinVar: RCV000037224, RCV000056766, RCV000157164, RCV001039932, RCV001250885, RCV003298065, RCV003398603, RCV003486560
|
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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 man who was diagnosed with dilated cardiomyopathy (CMD1I; 604765) at age 55 years, Taylor et al. (2007) identified heterozygosity for a c.1134C-T transition in the DES gene, resulting in an arg350-to-trp (R350W) substitution at a residue within the conserved alpha-helical coil of the 2B rod domain. DNA from family members was unavailable for analysis, but the mutation was not found in 300 control chromosomes. The proband, who was negative for mutation in 6 known CMD-associated genes, had no overt skeletal muscle involvement, and creatine kinase level was normal. Immunofluorescence microscopy of transfected SW13 cells, human coronary artery smooth muscle cells, and neonatal rat cardiac myocytes expressing the R350W mutation revealed severe disruption of the normal desmin cytoskeletal architecture in the majority of transfected cells, with clumping and aggregation of antibody-positive staining cytoplasmic protein. The mutation demonstrated a dominant phenotype in the human coronary artery smooth muscle cell lines, in which constitutively expressed desmin was unable to compensate for the presence of the R350W mutant. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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|
</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Ariza, A., Coll, J., Fernandez-Figueras, M. T., Lopez, M. D., Mate, J. L., Garcia, O., Fernandez-Vasalo, A., Navas-Palacios, J. J.
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|
<strong>Desmin myopathy: a multisystem disorder involving skeletal, cardiac, and smooth muscle.</strong>
|
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Hum. Path. 26: 1032-1037, 1995.
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[PubMed: 7672786]
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[Full Text: https://doi.org/10.1016/0046-8177(95)90095-0]
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</p>
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<li>
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<p class="mim-text-font">
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Bar, H., Fischer, D., Goudeau, B., Kley, R. A., Clemen, C. S., Vicart, P., Herrmann, H., Vorgerd, M., Schroeder, R.
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|
<strong>Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro.</strong>
|
|
Hum. Molec. Genet. 14: 1251-1260, 2005.
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[PubMed: 15800015]
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[Full Text: https://doi.org/10.1093/hmg/ddi136]
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<p class="mim-text-font">
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Bar, H., Goudeau, B., Walde, S., Casteras-Simon, M., Mucke, N., Shatunov, A., Goldberg, Y. P., Clarke, C., Holton, J. L., Eymard, B., Katus, H. A., Fardeau, M., Goldfarb, L., Vicart, P., Herrmann, H.
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<strong>Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies.</strong>
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Hum. Mutat. 28: 374-386, 2007.
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[PubMed: 17221859]
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[Full Text: https://doi.org/10.1002/humu.20459]
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</p>
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<li>
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<p class="mim-text-font">
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Bar, H., Mucke, N., Kostareva, A., Sjoberg, G., Aebi, U., Herrmann, H.
|
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<strong>Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages.</strong>
|
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Proc. Nat. Acad. Sci. 102: 15099-15104, 2005.
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[PubMed: 16217025]
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[Full Text: https://doi.org/10.1073/pnas.0504568102]
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</p>
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<li>
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<p class="mim-text-font">
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Bergman, J. E. H., Veenstra-Knol, H. E., van Essen, A. J., van Ravenswaaij, C. M. A., den Dunnen, W. F. A., van den Wijngaard, A., van Tintelen, J. P.
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<strong>Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.</strong>
|
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Europ. J. Med. Genet. 50: 355-366, 2007.
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[PubMed: 17720647]
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[Full Text: https://doi.org/10.1016/j.ejmg.2007.06.003]
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<li>
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<p class="mim-text-font">
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Cetin, N., Balci-Hayta, B., Gundesli, H., Korkusuz, P., Purali, N., Talim, B., Tan, E., Selcen, D., Erdem-Ozdamar, S., Dincer, P.
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<strong>A novel desmin mutation leading to autosomal recessive limb-girdle muscular dystrophy: distinct histopathological outcomes compared with desminopathies.</strong>
|
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J. Med. Genet. 50: 437-443, 2013.
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[PubMed: 23687351]
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[Full Text: https://doi.org/10.1136/jmedgenet-2012-101487]
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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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Dalakas, M. C., Park, K.-Y., Semino-Mora, C., Lee, H. S., Sivakumar, K., Goldfarb, L. G.
|
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<strong>Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene.</strong>
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New Eng. J. Med. 342: 770-780, 2000.
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[PubMed: 10717012]
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[Full Text: https://doi.org/10.1056/NEJM200003163421104]
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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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Goldfarb, L. G., Park, K.-Y., Cervenakova, L., Gorokhova, S., Lee, H.-S., Vasconcelos, O., Nagle, J. W., Semino-Mora, C., Sivakumar, K., Dalakas, M. C.
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<strong>Missense mutations in desmin associated with familial cardiac and skeletal myopathy.</strong>
|
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Nature Genet. 19: 402-403, 1998.
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[PubMed: 9697706]
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[Full Text: https://doi.org/10.1038/1300]
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</p>
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<li>
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<p class="mim-text-font">
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Goudeau, B., Dagvadorj, A., Rodrigues-Lima, F., Nedellec, P., Casteras-Simon, M., Perret, E., Langlois, S., Goldfarb, L., Vicart, P.
|
|
<strong>Structural and functional analysis of a new desmin variant causing desmin-related myopathy.</strong>
|
|
Hum. Mutat. 18: 388-396, 2001.
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|
[PubMed: 11668632]
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[Full Text: https://doi.org/10.1002/humu.1210]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Greenberg, S. A., Salajegheh, M., Judge, D. P., Feldman, M. W., Kuncl, R. W., Waldon, Z., Steen, H., Wagner, K. R.
|
|
<strong>Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics.</strong>
|
|
Ann. Neurol. 71: 141-145, 2012.
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[PubMed: 22275259]
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[Full Text: https://doi.org/10.1002/ana.22649]
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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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Hedberg, C., Melberg, A., Kuhl, A., Jenne, D., Oldfors, A.
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Wieneke, S., Stehle, R., Li, Z., Jockusch, H.
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<strong>Generation of tension by skinned fibers and intact skeletal muscles from desmin-deficient mice.</strong>
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Biochem. Biophys. Res. Commun. 278: 419-425, 2000.
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[PubMed: 11097852]
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[Full Text: https://doi.org/10.1006/bbrc.2000.3810]
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Contributors:
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Marla J. F. O'Neill - updated : 07/30/2020<br>Marla J. F. O'Neill - updated : 8/13/2014<br>Cassandra L. Kniffin - updated : 7/22/2013<br>Cassandra L. Kniffin - updated : 10/23/2012<br>Cassandra L. Kniffin - updated : 4/2/2012<br>Matthew B. Gross - updated : 2/17/2012<br>Patricia A. Hartz - updated : 2/14/2012<br>Marla J. F. O'Neill - updated : 3/12/2010<br>George E. Tiller - updated : 5/30/2008<br>Victor A. McKusick - updated : 2/19/2008<br>Cassandra L. Kniffin - updated : 5/23/2007<br>Patricia A. Hartz - updated : 7/17/2006<br>Patricia A. Hartz - updated : 1/27/2006<br>George E. Tiller - updated : 2/15/2005<br>Patricia A. Hartz - updated : 11/5/2004<br>Patricia A. Hartz - updated : 9/9/2004<br>Cassandra L. Kniffin - reorganized : 7/23/2004<br>Victor A. McKusick - updated : 2/9/2004<br>Patricia A. Hartz - updated : 6/6/2003<br>Kathryn R. Wagner - updated : 2/20/2001<br>Michael J. Wright - updated : 2/13/2001<br>Victor A. McKusick - updated : 8/21/2000<br>Victor A. McKusick - updated : 5/1/2000<br>Carol A. Bocchini - updated : 4/24/2000<br>Victor A. McKusick - updated : 11/19/1999<br>Paul Brennan - updated : 8/31/1999<br>Victor A. McKusick - updated : 10/5/1998<br>Victor A. McKusick - updated : 7/29/1998
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Victor A. McKusick : 6/4/1986
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