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<title>
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Entry
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- *602378 - DYNAMIN 2; DNM2
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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="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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<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 style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<a href="/history"> Search History </a>
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</form>
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<p />
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</div>
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*602378</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<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 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 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/602378">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 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=ENSG00000079805;t=ENST00000389253" 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=1785" 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=602378" 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=ENSG00000079805;t=ENST00000389253" 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_001005360,NM_001005361,NM_001005362,NM_001190716,NM_004945" 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_001005361" 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=602378" 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=03852&isoform_id=03852_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/DNM2" 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/1196423,4567174,4567175,21757772,32451865,34530791,34532605,34533762,47117856,56549119,56549121,56549123,56549125,56969514,62088006,119604550,119604551,119604552,119604553,119604554,119604555,119604556,119604557,158260685,193783649,193787763,194381522,299758394" 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/P50570" 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=1785" 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=ENSG00000079805;t=ENST00000389253" 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=DNM2" 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=DNM2" 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+1785" 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/DNM2" 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:1785" 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/1785" 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=chr19&hgg_gene=ENST00000389253.9&hgg_start=10718079&hgg_end=10831903&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:2974" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/dnm2" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602378[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=602378[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/ENSG00000079805" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=DNM2" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=DNM2" 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=DNM2" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/DNM2" title="Leiden Muscular Dystrophy pages" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Leiden Muscular Dystrophy …</a></div><div style="margin-left: 0.5em;"><a href="http://www.molgen.ua.ac.be/CMTMutations/" title="Inherited Peripheral Neuropathies Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Inherited Peripheral Neuro…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DNM2&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/PA27442" 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:2974" 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://flybase.org/reports/FBgn0003392.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:109547" 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/DNM2#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:109547" 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/1785/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002534/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1785" 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=WBGene00001130;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-040426-2371" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:602378" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1785" 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=DNM2&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> 763346009, 765745007<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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602378
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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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DYNAMIN 2; DNM2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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DYN2
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</span>
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</h4>
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</div>
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DNM2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DNM2</a></em></strong>
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Phenotype <br /> MIM number
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19p13.2
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Centronuclear myopathy 1
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<a href="/entry/160150"> 160150 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Charcot-Marie-Tooth disease, axonal type 2M
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<span class="mim-font">
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<a href="/entry/606482"> 606482 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Charcot-Marie-Tooth disease, dominant intermediate B
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<a href="/entry/606482"> 606482 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Lethal congenital contracture syndrome 5
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<a href="/entry/615368"> 615368 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/602378" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/602378" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>DNM2 is a ubiquitously expressed large GTPase involved in clathrin (see <a href="/entry/118955">118955</a>)-dependent and -independent endocytosis and intracellular membrane trafficking. DNM2 interacts tightly with actin and microtubule networks and may have a role in centrosome function (summary by <a href="#5" class="mim-tip-reference" title="Durieux, A.-C., Vignaud, A., Prudhon, B., Viou, M. T., Beuvin, M., Vassilopoulos, S., Fraysse, B., Ferry, A., Laine, J., Romero, N. B., Guicheney, P., Bitoun, M. <strong>A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.</strong> Hum. Molec. Genet. 19: 4820-4836, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20858595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20858595</a>] [<a href="https://doi.org/10.1093/hmg/ddq413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20858595">Durieux et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20858595" 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>Dynamins (DNMs) are members of a group of GTPases that share high homology in their N-terminal regions. Mammals have at least 3 DNMs: DNM1 (<a href="/entry/602377">602377</a>), DNM2, and DNM3 (<a href="/entry/611445">611445</a>). <a href="#4" class="mim-tip-reference" title="Diatloff-Zito, C., Gordon, A. J. E., Duchaud, E., Merlin, G. <strong>Isolation of an ubiquitously expressed cDNA encoding human dynamin II, a member of the large GTP-binding protein family.</strong> Gene 163: 301-306, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7590285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7590285</a>] [<a href="https://doi.org/10.1016/0378-1119(95)00275-b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7590285">Diatloff-Zito et al. (1995)</a> had previously isolated a human genomic DNA fragment by its capacity to correct the mitomycin C hypersensitivity of cells from a Fanconi anemia patient belonging to genetic complementation group D (FACD; <a href="/entry/227646">227646</a>). Using this fragment, they screened a human fibroblast cDNA library and isolated a cDNA encoding DNM2. The predicted 866-amino acid protein is 73% and 98% identical to DNM1 and rat Dnm2, respectively. It contains the 3 consensus sequence elements characteristic of GTP-binding proteins at its N terminus, a pleckstrin homology (PH) domain, and a basic, proline-rich C-terminal region that contains multiple SRC homology 3 domains. DNM2 contains 9 consensus motifs for CDC2 (<a href="/entry/116940">116940</a>) phosphorylation, indicating a potential role at the G2/mitosis transition. Northern blot analysis detected a 3.6-kb transcript in all tissues examined, with highest expression in heart and skeletal muscle. Sequencing and RT-PCR identified alternative splicing variants of DNM2. The authors suggested that multiple rounds of duplication and divergence occurred within DNM gene evolution. No alterations in DNM2 sequence or mRNA expression were detected in the FACD patient studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7590285" 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 in situ hybridization with a Dnm2 mRNA probe, <a href="#10" class="mim-tip-reference" title="Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J. <strong>Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.</strong> Europ. J. Hum. Genet. 21: 637-642, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23092955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23092955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23092955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23092955">Koutsopoulos et al. (2013)</a> found Dnm2 expression in most mouse embryonic tissues, including the peripheral nervous system, but not in skeletal muscle or heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23092955" 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="#8" class="mim-tip-reference" title="Gomez, T. S., Hamann, M. J., McCarney, S., Savoy, D. N., Lubking, C. M., Heldebrant, M. P., Labno, C. M., McKean, D. J., McNiven, M. A., Burkhardt, J. K., Billadeau, D. D. <strong>Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.</strong> Nature Immun. 6: 261-270, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15696170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15696170</a>] [<a href="https://doi.org/10.1038/ni1168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15696170">Gomez et al. (2005)</a> found that DYN2 accumulated at the T cell-antigen presenting cell (APC) interface in the presence of antigen. DYN2 knockdown experiments showed that DYN2 coupled T-cell receptor (TCR)-mediated signaling pathways to those regulating IL2 (<a href="/entry/147680">147680</a>) promoter activity and CD69 (<a href="/entry/107273">107273</a>) expression. Further experiments identified DYN2 as a critical regulator of the actin cytoskeleton in response to TCR engagement. The proline-rich domain of DYN2 interacted directly with the SH3 domain of VAV1 (<a href="/entry/164875">164875</a>), and this interaction was required for T-cell activation. <a href="#8" class="mim-tip-reference" title="Gomez, T. S., Hamann, M. J., McCarney, S., Savoy, D. N., Lubking, C. M., Heldebrant, M. P., Labno, C. M., McKean, D. J., McNiven, M. A., Burkhardt, J. K., Billadeau, D. D. <strong>Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.</strong> Nature Immun. 6: 261-270, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15696170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15696170</a>] [<a href="https://doi.org/10.1038/ni1168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15696170">Gomez et al. (2005)</a> concluded that DYN2 regulates actin reorganization at the immunologic synapse and links to VAV1 and its downstream signaling pathways after TCR engagement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15696170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Orth, J. D., McNiven, M. A. <strong>Dynamin at the actin-membrane interface.</strong> Curr. Opin. Cell Biol. 15: 31-39, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12517701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12517701</a>] [<a href="https://doi.org/10.1016/s0955-0674(02)00010-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12517701">Orth and McNiven (2003)</a> found that Dyn2 associated with amphiphysin (<a href="/entry/600418">600418</a>) on phagosomes in cultured cells. Expression of a GTPase-deficient Dyn2 mutant prevented vesiculation and induced the formation of long plasma membrane invaginations coated with the mutant protein and terminated with a clathrin tip or bulb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12517701" 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 studies in cultured mouse podocytes and rodent models of proteinuria, <a href="#13" class="mim-tip-reference" title="Sever, S., Altintas, M. M., Nankoe, S. R., Moller, C. C., Ko, D., Wei, C., Henderson, J., del Re, E. C., Hsing, L., Erickson, A., Cohen, C. D., Kretzler, M., Kerjaschki, D., Rudensky, A., Nikolic, B., Reiser, J. <strong>Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.</strong> J. Clin. Invest. 117: 2095-2104, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17671649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17671649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17671649[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI32022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17671649">Sever et al. (2007)</a> showed that during proteinuric kidney disease, induction of cytoplasmic cathepsin L (CTSL; <a href="/entry/116880">116880</a>) led to cleavage of dynamin at a conserved site between amino acids 354 and 359, resulting in reorganization of the podocyte actin cytoskeleton and proteinuria. Dynamin mutants that lacked the CTSL site, or rendered the CTSL site inaccessible through dynamin self-assembly, were resistant to CTSL cleavage. When delivered into mice, these mutants restored podocyte function and resolved proteinuria. <a href="#13" class="mim-tip-reference" title="Sever, S., Altintas, M. M., Nankoe, S. R., Moller, C. C., Ko, D., Wei, C., Henderson, J., del Re, E. C., Hsing, L., Erickson, A., Cohen, C. D., Kretzler, M., Kerjaschki, D., Rudensky, A., Nikolic, B., Reiser, J. <strong>Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.</strong> J. Clin. Invest. 117: 2095-2104, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17671649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17671649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17671649[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI32022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17671649">Sever et al. (2007)</a> concluded that dynamin is a critical regulator of renal permselectivity that is specifically targeted by proteolysis under pathologic conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17671649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Lee, J. E., Westrate, L. M., Wu, H., Page, C., Voeltz, G. K. <strong>Multiple dynamin family members collaborate to drive mitochondrial division.</strong> Nature 540: 139-143, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27798601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27798601</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27798601[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature20555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27798601">Lee et al. (2016)</a> reported that the ubiquitously expressed classical DYN2 is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy in 3 different mammalian cell lines revealed that DYN2 works in concert with DRP1 (<a href="/entry/603850">603850</a>) to orchestrate sequential constriction events that build up to division. <a href="#11" class="mim-tip-reference" title="Lee, J. E., Westrate, L. M., Wu, H., Page, C., Voeltz, G. K. <strong>Multiple dynamin family members collaborate to drive mitochondrial division.</strong> Nature 540: 139-143, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27798601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27798601</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27798601[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature20555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27798601">Lee et al. (2016)</a> concluded that their work underscores the biophysical limitations of DRP1 and positions DYN2, which has intrinsic membrane fission properties, at the final step of mitochondrial division. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27798601" 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="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a> determined that the DNM2 gene contains 22 exons, 20 of which are coding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731758" 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 interspecific backcross analysis, <a href="#9" class="mim-tip-reference" title="Klocke, R., Augustin, A., Ronsiek, M., Stief, A., van der Putten, H., Jockusch, H. <strong>Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively.</strong> Genomics 41: 290-292, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9143510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9143510</a>] [<a href="https://doi.org/10.1006/geno.1997.4634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9143510">Klocke et al. (1997)</a> found that the mouse Dnm2 gene is closely linked to the Icam1 gene (<a href="/entry/147840">147840</a>) on the proximal portion of chromosome 9, in a region with homologies to human 19p, 8q, and 11q. That the human ICAM1 gene is located on 19p13.3-p13.2 is evidence that the DNM2 gene is also in that region. The finding of mutations in the DNM2 gene in families with a form of autosomal dominant intermediate Charcot-Marie-Tooth disease (<a href="/entry/606482">606482</a>) that maps to 19p13.2-p12 is further confirmation of the mapping of DNM2 to chromosome 19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9143510" 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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Because the DNM2 gene maps to 19p13.2-p12 and shares domains similar to those of genes known to be involved in axonal Charcot-Marie-Tooth disease (see <a href="/entry/118210">118210</a>), <a href="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a> considered it a candidate gene for the form of dominant intermediate Charcot-Marie-Tooth disease that maps to chromosome 19p13.2-p12 (CMTDIB; <a href="/entry/606482">606482</a>). They identified 3 unique mutations in the DNM2 pleckstrin homology domain in 3 unrelated families with DI-CMTB. These mutations disturbed the function of DNM2 in a cellular model. DNM2 represented the third protein mutated in CMT that contains a GTPase domain and is related to fusion or fission of cellular membranes. In 2 of the families neutropenia cosegregated with the neuropathy; these families each had a mutation affecting lys558 (<a href="#0002">602378.0002</a>, <a href="#0003">602378.0003</a>), which suggested that this residue has a function in maturation or survival of peripheral blood cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731758" 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>Charcot-Marie-Tooth Disease Type 2M</em></strong></p><p>
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In affected members of a family with autosomal dominant Charcot-Marie-Tooth Disease (CMT2M; see <a href="/entry/606482">606482</a>), <a href="#6" class="mim-tip-reference" title="Fabrizi, G. M., Ferrarini, M., Cavallaro, T., Cabrini, I., Cerini, R., Bertolasi, L., Rizzuto, N. <strong>Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.</strong> Neurology 69: 291-295, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17636067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17636067</a>] [<a href="https://doi.org/10.1212/01.wnl.0000265820.51075.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17636067">Fabrizi et al. (2007)</a> identified a heterozygous missense mutation in the DNM2 gene (G533C; <a href="#0008">602378.0008</a>). The phenotype was milder than that reported for other CMT patients with DNM2 mutations and was more consistent with an axonal form of CMT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17636067" 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>Centronuclear Myopathy 1</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P. <strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong> Nature Genet. 37: 1207-1209, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16227997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16227997</a>] [<a href="https://doi.org/10.1038/ng1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16227997">Bitoun et al. (2005)</a> carried out genomewide linkage mapping analysis in 2 families with autosomal dominant centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), narrowing the CNM1 locus to an 11-Mb interval on 19p13.2. The DNM2 gene, which maps to this region, was considered a good candidate. Sequencing of exons and intron-exon boundaries in the probands of 3 families identified heterozygous mutations. Two were located in exon 8 and involved the same arg369 residue, (R369Q, <a href="#0004">602378.0004</a>; R369W, <a href="#0005">602378.0005</a>), and 1 was in exon 11 and involved an R465W mutation (<a href="#0006">602378.0006</a>). Another mutation, E368K (<a href="#0007">602378.0007</a>), was a de novo mutation in 1 family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16227997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Tosch, V., Rohde, H. M., Tronchere, H., Zanoteli, E., Monroy, N., Kretz, C., Dondaine, N., Payrastre, B., Mandel, J.-L., Laporte, J. <strong>A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.</strong> Hum. Molec. Genet. 15: 3098-3106, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17008356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17008356</a>] [<a href="https://doi.org/10.1093/hmg/ddl250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17008356">Tosch et al. (2006)</a> described a patient with centronuclear myopathy who carried heterozygous mutations in both the DNM2 (E368K; <a href="#0007">602378.0007</a>) and MTMR14 (Y462C; <a href="/entry/611089#0002">611089.0002</a>) genes. They noted that whereas centronuclear myopathy patients with other characterized mutations in DYN2 usually have an age of onset in childhood or adulthood, the age of onset in their patient was neonatal. The report raised the possibility of MTMR14 being a modifier of the phenotype in some cases of centronuclear myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17008356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bitoun, M., Bevilacqua, J. A., Prudhon, B., Maugenre, S., Taratuto, A. L., Monges, S., Lubieniecki, F., Cances, C., Uro-Coste, E., Mayer, M., Fardeau, M., Romero, N. B., Guicheney, P. <strong>Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.</strong> Ann. Neurol. 62: 666-670, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932957</a>] [<a href="https://doi.org/10.1002/ana.21235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17932957">Bitoun et al. (2007)</a> identified 4 different de novo heterozygous DNM2 mutations (see, e.g., <a href="#0010">602378.0010</a>; <a href="#0011">602378.0011</a>) in 5 unrelated patients with sporadic CNM. All mutations were in exon 16 of the DNM2 gene within the pleckstrin homology domain. Three of the patients had a severe disorder with onset at birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932957" 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 in vitro sedimentation assays, <a href="#15" class="mim-tip-reference" title="Wang, L., Barylko, B., Byers, C., Ross, J. A., Jameson, D. M., Albanesi, J. P. <strong>Dynamin 2 mutants linked to centronuclear myopathies form abnormally stable polymers.</strong> J. Biol. Chem. 285: 22753-22757, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20529869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20529869</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20529869[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/10.1074/jbc.C110.130013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20529869">Wang et al. (2010)</a> showed that centronuclear myopathy-associated mutant DNM2 proteins (see, e.g., <a href="#0005">602378.0005</a>-<a href="#0007">602378.0007</a>) formed more stable dynamin polymers in the presence of GTP compared to wildtype, presumably reflecting abnormally strong dynamin-dynamin interactions. The mutant protein aggregates were less sensitive to disassociation by GTP, and retained higher GTPase activities compared to wildtype. The observations suggested that the affected residues, such as glu368, arg369, and arg465, normally function to prevent excessive or prolonged dynamin assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20529869" 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>Lethal Congenital Contracture Syndrome 5</em></strong></p><p>
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In 3 sibs, born of consanguineous Pakistani parents, with lethal congenital contracture syndrome-5 (LCCS5; <a href="/entry/615368">615368</a>), <a href="#10" class="mim-tip-reference" title="Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J. <strong>Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.</strong> Europ. J. Hum. Genet. 21: 637-642, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23092955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23092955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23092955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23092955">Koutsopoulos et al. (2013)</a> identified a homozygous missense mutation in the DNM2 gene (F379V; <a href="#0013">602378.0013</a>). The infants all showed severe hypotonia with lack of spontaneous movement and respiratory insufficiency at birth, resulting in death in a few days to months. Each also showed retinal hemorrhages. Studies on patient cells and in vitro functional analysis indicated that the mutation was hypomorphic. Animal studies in mice and zebrafish suggested a role for Dnm2 in the development of muscle fibers and vasculature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23092955" 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 homologous recombination, <a href="#5" class="mim-tip-reference" title="Durieux, A.-C., Vignaud, A., Prudhon, B., Viou, M. T., Beuvin, M., Vassilopoulos, S., Fraysse, B., Ferry, A., Laine, J., Romero, N. B., Guicheney, P., Bitoun, M. <strong>A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.</strong> Hum. Molec. Genet. 19: 4820-4836, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20858595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20858595</a>] [<a href="https://doi.org/10.1093/hmg/ddq413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20858595">Durieux et al. (2010)</a> developed a line of mice expressing human DNM2 with the R465W substitution (<a href="#0006">602378.0006</a>). The vast majority of homozygous mutants died during the first hours of life. Homozygous mutant muscle fibers showed multiple structural abnormalities, disorganized intermyofibrillar networks, and loss of oxidative enzyme activity. Homozygous mutant embryonic fibroblasts showed impaired clathrin-mediated endocytosis. Heterozygous R465W mice showed normal development and locomotor activity and lived as long as wildtype littermates. However, they developed atrophy of the tibialis anterior muscle at 2 months, concomitant with impaired contractile properties and development of muscle weakness, and atrophy progressed to other muscles at 8 months. DNM2-R465W protein was expressed at wildtype levels and showed normal transversal striated pattern along the I band and expression in several other muscle regions, including sarcoplasm, perinuclear region, and postsynaptic region of the neuromuscular junction. Histopathologic abnormalities mainly affected mitochondria and reticular networks. Heterozygous R465W fibers also showed increased calcium concentration and intracellular Dnm2 and dysferlin (DYSF; <a href="/entry/603009">603009</a>) accumulation. A similar accumulation of DYSF was found in biopsies from centronuclear myopathy patients with mutations in the DNM2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20858595" 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="#10" class="mim-tip-reference" title="Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J. <strong>Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.</strong> Europ. J. Hum. Genet. 21: 637-642, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23092955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23092955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23092955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23092955">Koutsopoulos et al. (2013)</a> found that morpholino knockdown of Dnm2 in zebrafish embryos resulted in lethality in 10% and bent tails in 20%. Morphant muscle fibers showed mild misalignment of muscle fibers; muscular innervation appeared normal. There were also defects in the endothelium of the vascular system. The findings suggested that Dnm2 has a pleiotropic role during development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23092955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a North American family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIB; <a href="/entry/606482">606482</a>), <a href="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a> found a 9-bp deletion of the 3-prime end of exon 14 of the DNM2 gene (1652_1659+1delATGAGGAGg). The mutation was predicted to result in 2 alternative mRNA products, one with a premature stop codon resulting from a shift of the open reading frame (D550fs) and the other an in-frame mRNA with a predicted deletion of 3 amino acids (D551_E553del) produced by disruption of the original 3-prime splice site and use of a newly introduced splice site with higher predicted splicing activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731758" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In an Australian family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIB; <a href="/entry/606482">606482</a>), <a href="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a> found that affected individuals carried a mutation in exon 15 of the DNM2 gene, 1672A-G, resulting in the amino acid substitution lys558-to-glu (K558E). Subclinically low counts of neutrophils and, in some affected individuals, few lymphocytes, erythrocytes, and platelets cosegregated with CMT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731758" 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">rs1599620408 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1599620408;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=rs1599620408" 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=rs1599620408" 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=RCV000789092 OR RCV001560332 OR RCV001869214 OR RCV002285173 OR RCV002397560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000789092, RCV001560332, RCV001869214, RCV002285173, RCV002397560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000789092...</a>
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<p>In a Belgian family with dominant intermediate Charcot-Marie-Tooth disease and associated neutropenia (CMTDIB; <a href="/entry/606482">606482</a>), <a href="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a> identified a deletion of nucleotides 1672 through 1674 (1672_1674delAAG) in the DNM2 gene, resulting in deletion of a single amino acid, lys558. That an abnormality of lys558 was found in 2 families (see also <a href="#0002">602378.0002</a>) in which neutropenia, not a general feature of dominant intermediate Charcot-Marie-Tooth disease, cosegregated with the neuropathy implied that this residue has a function in maturation or survival of peripheral blood cells. Congenital neutropenia (<a href="/entry/202700">202700</a>) is caused by mutations in the gene elastase-2 gene (ELA2; <a href="/entry/130130">130130</a>), which maps to 19p13.3. In the Belgian family, <a href="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a> excluded mutations in ELA2 as the cause of neutropenia by sequence analysis of all coding exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731758" 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 follow-up of the Belgian family reported by <a href="#16" class="mim-tip-reference" title="Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M. <strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong> Nature Genet. 37: 289-294, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>] [<a href="https://doi.org/10.1038/ng1514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731758">Zuchner et al. (2005)</a>, <a href="#3" class="mim-tip-reference" title="Claeys, K. G., Zuchner, S., Kennerson, M., Berciano, J., Garcia, A., Verhoeven, K., Storey, E., Merory, J. R., Bienfait, H. M. E., Lammens, M., Nelis, E., Baets, J., De Vriendt, E., Berneman, Z. N., De Veuster, I., Vance, J. M., Nicholson, G., Timmerman, V., De Jonghe, P. <strong>Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.</strong> Brain 132: 1741-1752, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19502294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19502294</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19502294[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awp115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19502294">Claeys et al. (2009)</a> found that 1 mutation carrier had neutropenia and cataracts without signs of a neuropathy. In addition, 5 members of this family had early-onset cataracts in their teenage years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15731758+19502294" 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">rs121909089 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909089;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=rs121909089" 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=rs121909089" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 14 members of a family from French Guyana with autosomal dominant centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), <a href="#2" class="mim-tip-reference" title="Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P. <strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong> Nature Genet. 37: 1207-1209, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16227997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16227997</a>] [<a href="https://doi.org/10.1038/ng1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16227997">Bitoun et al. (2005)</a> identified a heterozygous 1106G-A mutation in exon 8 of the DNM2 gene, resulting in an arg369-to-gln (R369Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16227997" 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> rs121909090 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909090;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/rs121909090?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=rs121909090" 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=rs121909090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a French family with autosomal dominant centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), <a href="#2" class="mim-tip-reference" title="Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P. <strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong> Nature Genet. 37: 1207-1209, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16227997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16227997</a>] [<a href="https://doi.org/10.1038/ng1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16227997">Bitoun et al. (2005)</a> identified a heterozygous 1105C-to-T transition in exon 8 of the DNM2 gene that resulted in an arg369-to-trp (R369W) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16227997" 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">rs121909091 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909091;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=rs121909091" 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=rs121909091" 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=RCV000007704 OR RCV000145902 OR RCV000373773 OR RCV000641110 OR RCV001813964 OR RCV004745149" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007704, RCV000145902, RCV000373773, RCV000641110, RCV001813964, RCV004745149" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007704...</a>
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<p>In affected members of a French family with autosomal dominant centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), <a href="#2" class="mim-tip-reference" title="Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P. <strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong> Nature Genet. 37: 1207-1209, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16227997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16227997</a>] [<a href="https://doi.org/10.1038/ng1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16227997">Bitoun et al. (2005)</a> identified a heterozygous 1393C-T transition in exon 11 of the DNM2 gene, resulting in an arg465-to-trp (R465W) substitution. This mutation was found in 5 additional families with CNM1, 2 Belgian, 1 German, 1 from Great Britain, and 1 from the United States. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16227997" 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> rs121909092 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909092;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/rs121909092?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=rs121909092" 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=rs121909092" 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=RCV000007705 OR RCV000145898 OR RCV000554046 OR RCV000626717 OR RCV000725988 OR RCV003914819" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007705, RCV000145898, RCV000554046, RCV000626717, RCV000725988, RCV003914819" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007705...</a>
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<p>In a French proband with centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), <a href="#2" class="mim-tip-reference" title="Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P. <strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong> Nature Genet. 37: 1207-1209, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16227997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16227997</a>] [<a href="https://doi.org/10.1038/ng1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16227997">Bitoun et al. (2005)</a> identified a heterozygous 1102G-to-A transition in exon 8 of the DNM2 gene that resulted in a glu368-to-lys (E368K) substitution. The mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16227997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Tosch, V., Rohde, H. M., Tronchere, H., Zanoteli, E., Monroy, N., Kretz, C., Dondaine, N., Payrastre, B., Mandel, J.-L., Laporte, J. <strong>A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.</strong> Hum. Molec. Genet. 15: 3098-3106, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17008356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17008356</a>] [<a href="https://doi.org/10.1093/hmg/ddl250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17008356">Tosch et al. (2006)</a> reported this mutation in heterozygosity in a 36-year-old woman with centronuclear myopathy who presented with neonatal hypotonia, muscle weakness, and ophthalmoparesis. She also carried a heterozygous missense mutation in the myotubularin-related protein-14 gene (MTMR14; <a href="/entry/611089#0002">611089.0002</a>). Both mutations occurred de novo. The report raised the possibility of MTMR14 being a modifier of the phenotype in some cases of centronuclear myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17008356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M</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">rs121909093 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909093;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=rs121909093" 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=rs121909093" 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=RCV000007706 OR RCV000789617 OR RCV003447077" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007706, RCV000789617, RCV003447077" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007706...</a>
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<p>In affected members of a family with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see <a href="/entry/606482">606482</a>), <a href="#6" class="mim-tip-reference" title="Fabrizi, G. M., Ferrarini, M., Cavallaro, T., Cabrini, I., Cerini, R., Bertolasi, L., Rizzuto, N. <strong>Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.</strong> Neurology 69: 291-295, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17636067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17636067</a>] [<a href="https://doi.org/10.1212/01.wnl.0000265820.51075.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17636067">Fabrizi et al. (2007)</a> identified a heterozygous 1597G-T transversion in the DNM2 gene, resulting in a gly533-to-cys (G533C) substitution. The phenotype was milder than that reported for other CMT patients with DNM2 mutations and was more consistent with an axonal form of CMT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17636067" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M</strong>
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DNM2, LEU566HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909094 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909094;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=rs121909094" 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=rs121909094" 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=RCV000007707 OR RCV000789619 OR RCV003447078" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007707, RCV000789619, RCV003447078" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007707...</a>
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<p>In a 45-year-old proband of a family with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see <a href="/entry/606482">606482</a>), <a href="#6" class="mim-tip-reference" title="Fabrizi, G. M., Ferrarini, M., Cavallaro, T., Cabrini, I., Cerini, R., Bertolasi, L., Rizzuto, N. <strong>Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.</strong> Neurology 69: 291-295, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17636067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17636067</a>] [<a href="https://doi.org/10.1212/01.wnl.0000265820.51075.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17636067">Fabrizi et al. (2007)</a> identified a heterozygous 1697T-A transversion in the DNM2 gene, resulting in a leu566-to-his (L566H) substitution. The phenotype was milder than that reported for other CMT patients with DNM2 mutations and was more consistent with an axonal form of CMT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17636067" 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, CENTRONUCLEAR, 1</strong>
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DNM2, SER619LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909095 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909095;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=rs121909095" 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=rs121909095" 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=RCV000007708 OR RCV000145908 OR RCV000544279 OR RCV000656268 OR RCV000754751 OR RCV002504764" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007708, RCV000145908, RCV000544279, RCV000656268, RCV000754751, RCV002504764" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007708...</a>
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<p>In 2 unrelated patients with sporadic centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), <a href="#1" class="mim-tip-reference" title="Bitoun, M., Bevilacqua, J. A., Prudhon, B., Maugenre, S., Taratuto, A. L., Monges, S., Lubieniecki, F., Cances, C., Uro-Coste, E., Mayer, M., Fardeau, M., Romero, N. B., Guicheney, P. <strong>Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.</strong> Ann. Neurol. 62: 666-670, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932957</a>] [<a href="https://doi.org/10.1002/ana.21235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17932957">Bitoun et al. (2007)</a> identified a de novo heterozygous 1856C-T transition in exon 16 of the DNM2 gene, resulting in a ser619-to-leu (S619L) substitution within the pleckstrin homology domain. Both patients had a severe phenotype, with onset at birth necessitating ventilation and nasogastric feeding, and delayed motor development. Another unrelated patient with a milder phenotype had a different heterozygous mutation in the same codon (S619W; <a href="#0011">602378.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932957" 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>.0011 MYOPATHY, CENTRONUCLEAR, 1</strong>
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DNM2, SER619TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909095 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909095;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=rs121909095" 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=rs121909095" 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=RCV000007709 OR RCV003441708 OR RCV003447079" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007709, RCV003441708, RCV003447079" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007709...</a>
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<p>In a patient with sporadic centronuclear myopathy (CNM1; <a href="/entry/160150">160150</a>), <a href="#1" class="mim-tip-reference" title="Bitoun, M., Bevilacqua, J. A., Prudhon, B., Maugenre, S., Taratuto, A. L., Monges, S., Lubieniecki, F., Cances, C., Uro-Coste, E., Mayer, M., Fardeau, M., Romero, N. B., Guicheney, P. <strong>Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.</strong> Ann. Neurol. 62: 666-670, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932957</a>] [<a href="https://doi.org/10.1002/ana.21235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17932957">Bitoun et al. (2007)</a> identified a de novo heterozygous 1856C-G transversion in exon 16 of the DNM2 gene, resulting in a ser619-to-trp (S619W) substitution. Two other unrelated patients with a more severe phenotype had a different heterozygous mutation in the same codon (S619L; <a href="#0010">602378.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932957" 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 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M</strong>
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DNM2, GLY358ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606772 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606772;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=rs267606772" 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=rs267606772" 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=RCV000007710 OR RCV000203266 OR RCV000369987" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007710, RCV000203266, RCV000369987" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007710...</a>
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<p>In a mother and her 2 adult daughters with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see <a href="/entry/606482">606482</a>), <a href="#7" class="mim-tip-reference" title="Gallardo, E., Claeys, K. G., Nelis, E., Garcia, A., Canga, A., Combarros, O., Timmerman, V., De Jonghe, P., Berciano, J. <strong>Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation.</strong> J. Neurol. 255: 986-992, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18560793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18560793</a>] [<a href="https://doi.org/10.1007/s00415-008-0808-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18560793">Gallardo et al. (2008)</a> identified a heterozygous 1072G-A transition in exon 7 of the DNM2 gene, resulting in a gly358-to-arg (G358R) substitution in a highly conserved region in the middle domain. The patients were ages 55, 32, and 23, and motor nerve conduction velocities were 33, 46, and 50 m/s, respectively. All had progressive gait unsteadiness and foot deformities, including pes cavus and toe clawing, in the first decade of life. All had distal muscle weakness and atrophy of the lower limbs, and the mother also had hand weakness and atrophy. Ankle reflexes were absent in all 3, and all had hypoesthesia of the lower limbs. MRI studies showed fatty infiltration of the calf muscles, particularly in the anterior compartment. The fatty infiltration increased distally and was massive in the foot musculature. Muscle edema was also present in affected muscles. In a follow-up of the family reported by <a href="#7" class="mim-tip-reference" title="Gallardo, E., Claeys, K. G., Nelis, E., Garcia, A., Canga, A., Combarros, O., Timmerman, V., De Jonghe, P., Berciano, J. <strong>Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation.</strong> J. Neurol. 255: 986-992, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18560793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18560793</a>] [<a href="https://doi.org/10.1007/s00415-008-0808-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18560793">Gallardo et al. (2008)</a>, <a href="#3" class="mim-tip-reference" title="Claeys, K. G., Zuchner, S., Kennerson, M., Berciano, J., Garcia, A., Verhoeven, K., Storey, E., Merory, J. R., Bienfait, H. M. E., Lammens, M., Nelis, E., Baets, J., De Vriendt, E., Berneman, Z. N., De Veuster, I., Vance, J. M., Nicholson, G., Timmerman, V., De Jonghe, P. <strong>Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.</strong> Brain 132: 1741-1752, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19502294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19502294</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19502294[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awp115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19502294">Claeys et al. (2009)</a> stated that the phenotype was consistent with axonal CMT2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19502294+18560793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 LETHAL CONGENITAL CONTRACTURE SYNDROME 5 (1 family)</strong>
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DNM2, PHE379VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514735 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514735;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=rs397514735" 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=rs397514735" 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=RCV000054501 OR RCV003447110" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054501, RCV003447110" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054501...</a>
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<p>In 3 sibs, born of consanguineous Pakistani parents, with lethal congenital contracture syndrome-5 (LCCS5; <a href="/entry/615368">615368</a>), <a href="#10" class="mim-tip-reference" title="Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J. <strong>Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.</strong> Europ. J. Hum. Genet. 21: 637-642, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23092955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23092955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23092955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23092955">Koutsopoulos et al. (2013)</a> identified a homozygous c.1135T-G transversion in exon 9 of the DNM2 gene, resulting in a phe379-to-val (F379V) substitution at a highly conserved residue in the middle domain of the protein. The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, was not present in 100 Pakistani controls and was absent from SNP databases. Patient fibroblasts showed a 20% reduction in DNM2-dependent endocytosis, and recombinant F379V DNM2 showed a 20% reduction in GTPase activity, consistent with its being a hypomorphic allele. The patients showed decreased fetal movements and severe hypotonia with respiratory insufficiency at birth. They had areflexia, lack of spontaneous movement, joint contractures, and thin ribs and bones. In addition, all had retinal hemorrhages and 2 had evidence of intracranial bleeding (subdural hematoma and blood in the subarachnoid cavity). Muscle biopsy of 1 patient showed small rounded fibers with some centralized nuclei, suggestive of a congenital myopathy component, whereas muscle biopsy of another patient showed atrophic fibers without obvious centralization of nuclei. EMG studies of 1 patient suggested a myopathy or lower motor neuron disease, whereas in the other 2 patients, EMG revealed low nerve conduction velocities, suggesting a hypomyelinating neuropathy or anterior horn disease. Death occurred at ages 5 days, 19 days, and 4 months. Both parents showed decreased reflexes on examination, and skeletal muscle biopsy of the mother showed fiber size variation and centralized nuclei, suggestive of a mild form of centronuclear myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23092955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Bitoun2007" class="mim-anchor"></a>
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Bitoun, M., Bevilacqua, J. A., Prudhon, B., Maugenre, S., Taratuto, A. L., Monges, S., Lubieniecki, F., Cances, C., Uro-Coste, E., Mayer, M., Fardeau, M., Romero, N. B., Guicheney, P.
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<strong>Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.</strong>
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Ann. Neurol. 62: 666-670, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.21235" target="_blank">Full Text</a>]
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<a id="Bitoun2005" class="mim-anchor"></a>
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Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P.
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<strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong>
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Nature Genet. 37: 1207-1209, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16227997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16227997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16227997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1657" target="_blank">Full Text</a>]
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<a id="Claeys2009" class="mim-anchor"></a>
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Claeys, K. G., Zuchner, S., Kennerson, M., Berciano, J., Garcia, A., Verhoeven, K., Storey, E., Merory, J. R., Bienfait, H. M. E., Lammens, M., Nelis, E., Baets, J., De Vriendt, E., Berneman, Z. N., De Veuster, I., Vance, J. M., Nicholson, G., Timmerman, V., De Jonghe, P.
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<strong>Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.</strong>
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Brain 132: 1741-1752, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19502294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19502294</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19502294[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19502294" 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/awp115" target="_blank">Full Text</a>]
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<a id="Diatloff-Zito1995" class="mim-anchor"></a>
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Diatloff-Zito, C., Gordon, A. J. E., Duchaud, E., Merlin, G.
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<strong>Isolation of an ubiquitously expressed cDNA encoding human dynamin II, a member of the large GTP-binding protein family.</strong>
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Gene 163: 301-306, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7590285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7590285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7590285" 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/10.1016/0378-1119(95)00275-b" target="_blank">Full Text</a>]
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<a id="Durieux2010" class="mim-anchor"></a>
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Durieux, A.-C., Vignaud, A., Prudhon, B., Viou, M. T., Beuvin, M., Vassilopoulos, S., Fraysse, B., Ferry, A., Laine, J., Romero, N. B., Guicheney, P., Bitoun, M.
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<strong>A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.</strong>
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Hum. Molec. Genet. 19: 4820-4836, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20858595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20858595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20858595" 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/ddq413" target="_blank">Full Text</a>]
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<a id="Fabrizi2007" class="mim-anchor"></a>
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Fabrizi, G. M., Ferrarini, M., Cavallaro, T., Cabrini, I., Cerini, R., Bertolasi, L., Rizzuto, N.
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<strong>Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.</strong>
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Neurology 69: 291-295, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17636067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17636067</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17636067" 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/10.1212/01.wnl.0000265820.51075.61" target="_blank">Full Text</a>]
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<a id="Gallardo2008" class="mim-anchor"></a>
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<div class="">
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Gallardo, E., Claeys, K. G., Nelis, E., Garcia, A., Canga, A., Combarros, O., Timmerman, V., De Jonghe, P., Berciano, J.
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<strong>Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation.</strong>
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J. Neurol. 255: 986-992, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18560793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18560793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18560793" 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/s00415-008-0808-8" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Gomez2005" class="mim-anchor"></a>
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Gomez, T. S., Hamann, M. J., McCarney, S., Savoy, D. N., Lubking, C. M., Heldebrant, M. P., Labno, C. M., McKean, D. J., McNiven, M. A., Burkhardt, J. K., Billadeau, D. D.
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<strong>Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.</strong>
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Nature Immun. 6: 261-270, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15696170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15696170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15696170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ni1168" target="_blank">Full Text</a>]
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<a id="Klocke1997" class="mim-anchor"></a>
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Klocke, R., Augustin, A., Ronsiek, M., Stief, A., van der Putten, H., Jockusch, H.
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<strong>Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively.</strong>
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Genomics 41: 290-292, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9143510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9143510</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9143510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1997.4634" target="_blank">Full Text</a>]
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<a id="Koutsopoulos2013" class="mim-anchor"></a>
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Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J.
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<strong>Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.</strong>
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Europ. J. Hum. Genet. 21: 637-642, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23092955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23092955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23092955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23092955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2012.226" target="_blank">Full Text</a>]
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<a id="Lee2016" class="mim-anchor"></a>
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<div class="">
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Lee, J. E., Westrate, L. M., Wu, H., Page, C., Voeltz, G. K.
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<strong>Multiple dynamin family members collaborate to drive mitochondrial division.</strong>
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Nature 540: 139-143, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27798601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27798601</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27798601[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27798601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature20555" target="_blank">Full Text</a>]
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Orth, J. D., McNiven, M. A.
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<strong>Dynamin at the actin-membrane interface.</strong>
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Curr. Opin. Cell Biol. 15: 31-39, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12517701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12517701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12517701" 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/s0955-0674(02)00010-8" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
|
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<a id="Sever2007" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Sever, S., Altintas, M. M., Nankoe, S. R., Moller, C. C., Ko, D., Wei, C., Henderson, J., del Re, E. C., Hsing, L., Erickson, A., Cohen, C. D., Kretzler, M., Kerjaschki, D., Rudensky, A., Nikolic, B., Reiser, J.
|
|
<strong>Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.</strong>
|
|
J. Clin. Invest. 117: 2095-2104, 2007.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17671649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17671649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17671649[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17671649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI32022" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Tosch2006" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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|
Tosch, V., Rohde, H. M., Tronchere, H., Zanoteli, E., Monroy, N., Kretz, C., Dondaine, N., Payrastre, B., Mandel, J.-L., Laporte, J.
|
|
<strong>A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.</strong>
|
|
Hum. Molec. Genet. 15: 3098-3106, 2006.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17008356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17008356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17008356" 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/ddl250" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Wang2010" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Wang, L., Barylko, B., Byers, C., Ross, J. A., Jameson, D. M., Albanesi, J. P.
|
|
<strong>Dynamin 2 mutants linked to centronuclear myopathies form abnormally stable polymers.</strong>
|
|
J. Biol. Chem. 285: 22753-22757, 2010.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20529869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20529869</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20529869[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20529869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.C110.130013" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Zuchner2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M.
|
|
<strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong>
|
|
Nature Genet. 37: 289-294, 2005.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731758</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731758" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/ng1514" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Ada Hamosh - updated : 10/02/2019
|
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Patricia A. Hartz - updated : 1/15/2014<br>Cassandra L. Kniffin - updated : 8/13/2013<br>Cassandra L. Kniffin - updated : 10/1/2010<br>Cassandra L. Kniffin - updated : 3/1/2010<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Cassandra L. Kniffin - updated : 1/15/2008<br>Marla J. F. O'Neill - updated : 12/21/2007<br>Patricia A. Hartz - updated : 8/22/2007<br>George E. Tiller - updated : 7/19/2007<br>Paul J. Converse - updated : 5/2/2006<br>Victor A. McKusick - updated : 11/1/2005<br>Victor A. McKusick - updated : 2/4/2005
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
|
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
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Patti M. Sherman : 2/23/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 02/21/2023
|
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</span>
|
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</div>
|
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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carol : 08/25/2020<br>carol : 08/24/2020<br>alopez : 10/02/2019<br>carol : 06/24/2016<br>carol : 3/9/2015<br>mgross : 1/16/2014<br>mcolton : 1/15/2014<br>carol : 8/15/2013<br>carol : 8/15/2013<br>ckniffin : 8/13/2013<br>carol : 12/29/2011<br>ckniffin : 12/22/2011<br>wwang : 10/7/2010<br>ckniffin : 10/1/2010<br>carol : 3/2/2010<br>carol : 3/2/2010<br>ckniffin : 3/1/2010<br>wwang : 4/4/2008<br>ckniffin : 3/31/2008<br>wwang : 1/31/2008<br>ckniffin : 1/15/2008<br>wwang : 1/8/2008<br>terry : 12/21/2007<br>alopez : 9/17/2007<br>terry : 8/22/2007<br>alopez : 7/19/2007<br>alopez : 2/1/2007<br>mgross : 5/5/2006<br>terry : 5/2/2006<br>alopez : 11/3/2005<br>terry : 11/1/2005<br>alopez : 3/2/2005<br>alopez : 2/9/2005<br>alopez : 2/9/2005<br>terry : 2/4/2005<br>psherman : 5/22/1998<br>dholmes : 2/23/1998
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 602378
|
|
</span>
|
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</h3>
|
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</div>
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<div>
|
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<h3>
|
|
<span class="mim-font">
|
|
|
|
DYNAMIN 2; DNM2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
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</div>
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<div>
|
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<div >
|
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DYN2
|
|
</span>
|
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</h4>
|
|
</div>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: DNM2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 763346009, 765745007;
|
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 19p13.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 19:10,718,079-10,831,903 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
19p13.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Centronuclear myopathy 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
160150
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, axonal type 2M
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
606482
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, dominant intermediate B
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
606482
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Lethal congenital contracture syndrome 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615368
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>DNM2 is a ubiquitously expressed large GTPase involved in clathrin (see 118955)-dependent and -independent endocytosis and intracellular membrane trafficking. DNM2 interacts tightly with actin and microtubule networks and may have a role in centrosome function (summary by Durieux et al., 2010). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
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|
<p>Dynamins (DNMs) are members of a group of GTPases that share high homology in their N-terminal regions. Mammals have at least 3 DNMs: DNM1 (602377), DNM2, and DNM3 (611445). Diatloff-Zito et al. (1995) had previously isolated a human genomic DNA fragment by its capacity to correct the mitomycin C hypersensitivity of cells from a Fanconi anemia patient belonging to genetic complementation group D (FACD; 227646). Using this fragment, they screened a human fibroblast cDNA library and isolated a cDNA encoding DNM2. The predicted 866-amino acid protein is 73% and 98% identical to DNM1 and rat Dnm2, respectively. It contains the 3 consensus sequence elements characteristic of GTP-binding proteins at its N terminus, a pleckstrin homology (PH) domain, and a basic, proline-rich C-terminal region that contains multiple SRC homology 3 domains. DNM2 contains 9 consensus motifs for CDC2 (116940) phosphorylation, indicating a potential role at the G2/mitosis transition. Northern blot analysis detected a 3.6-kb transcript in all tissues examined, with highest expression in heart and skeletal muscle. Sequencing and RT-PCR identified alternative splicing variants of DNM2. The authors suggested that multiple rounds of duplication and divergence occurred within DNM gene evolution. No alterations in DNM2 sequence or mRNA expression were detected in the FACD patient studied. </p><p>By in situ hybridization with a Dnm2 mRNA probe, Koutsopoulos et al. (2013) found Dnm2 expression in most mouse embryonic tissues, including the peripheral nervous system, but not in skeletal muscle or heart. </p>
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</span>
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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>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>Gomez et al. (2005) found that DYN2 accumulated at the T cell-antigen presenting cell (APC) interface in the presence of antigen. DYN2 knockdown experiments showed that DYN2 coupled T-cell receptor (TCR)-mediated signaling pathways to those regulating IL2 (147680) promoter activity and CD69 (107273) expression. Further experiments identified DYN2 as a critical regulator of the actin cytoskeleton in response to TCR engagement. The proline-rich domain of DYN2 interacted directly with the SH3 domain of VAV1 (164875), and this interaction was required for T-cell activation. Gomez et al. (2005) concluded that DYN2 regulates actin reorganization at the immunologic synapse and links to VAV1 and its downstream signaling pathways after TCR engagement. </p><p>Orth and McNiven (2003) found that Dyn2 associated with amphiphysin (600418) on phagosomes in cultured cells. Expression of a GTPase-deficient Dyn2 mutant prevented vesiculation and induced the formation of long plasma membrane invaginations coated with the mutant protein and terminated with a clathrin tip or bulb. </p><p>In studies in cultured mouse podocytes and rodent models of proteinuria, Sever et al. (2007) showed that during proteinuric kidney disease, induction of cytoplasmic cathepsin L (CTSL; 116880) led to cleavage of dynamin at a conserved site between amino acids 354 and 359, resulting in reorganization of the podocyte actin cytoskeleton and proteinuria. Dynamin mutants that lacked the CTSL site, or rendered the CTSL site inaccessible through dynamin self-assembly, were resistant to CTSL cleavage. When delivered into mice, these mutants restored podocyte function and resolved proteinuria. Sever et al. (2007) concluded that dynamin is a critical regulator of renal permselectivity that is specifically targeted by proteolysis under pathologic conditions. </p><p>Lee et al. (2016) reported that the ubiquitously expressed classical DYN2 is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy in 3 different mammalian cell lines revealed that DYN2 works in concert with DRP1 (603850) to orchestrate sequential constriction events that build up to division. Lee et al. (2016) concluded that their work underscores the biophysical limitations of DRP1 and positions DYN2, which has intrinsic membrane fission properties, at the final step of mitochondrial division. </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>Zuchner et al. (2005) determined that the DNM2 gene contains 22 exons, 20 of which are coding. </p>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By interspecific backcross analysis, Klocke et al. (1997) found that the mouse Dnm2 gene is closely linked to the Icam1 gene (147840) on the proximal portion of chromosome 9, in a region with homologies to human 19p, 8q, and 11q. That the human ICAM1 gene is located on 19p13.3-p13.2 is evidence that the DNM2 gene is also in that region. The finding of mutations in the DNM2 gene in families with a form of autosomal dominant intermediate Charcot-Marie-Tooth disease (606482) that maps to 19p13.2-p12 is further confirmation of the mapping of DNM2 to chromosome 19. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Charcot-Marie-Tooth Disease, Dominant Intermediate B</em></strong></p><p>
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Because the DNM2 gene maps to 19p13.2-p12 and shares domains similar to those of genes known to be involved in axonal Charcot-Marie-Tooth disease (see 118210), Zuchner et al. (2005) considered it a candidate gene for the form of dominant intermediate Charcot-Marie-Tooth disease that maps to chromosome 19p13.2-p12 (CMTDIB; 606482). They identified 3 unique mutations in the DNM2 pleckstrin homology domain in 3 unrelated families with DI-CMTB. These mutations disturbed the function of DNM2 in a cellular model. DNM2 represented the third protein mutated in CMT that contains a GTPase domain and is related to fusion or fission of cellular membranes. In 2 of the families neutropenia cosegregated with the neuropathy; these families each had a mutation affecting lys558 (602378.0002, 602378.0003), which suggested that this residue has a function in maturation or survival of peripheral blood cells. </p><p><strong><em>Charcot-Marie-Tooth Disease Type 2M</em></strong></p><p>
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In affected members of a family with autosomal dominant Charcot-Marie-Tooth Disease (CMT2M; see 606482), Fabrizi et al. (2007) identified a heterozygous missense mutation in the DNM2 gene (G533C; 602378.0008). The phenotype was milder than that reported for other CMT patients with DNM2 mutations and was more consistent with an axonal form of CMT. </p><p><strong><em>Centronuclear Myopathy 1</em></strong></p><p>
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Bitoun et al. (2005) carried out genomewide linkage mapping analysis in 2 families with autosomal dominant centronuclear myopathy (CNM1; 160150), narrowing the CNM1 locus to an 11-Mb interval on 19p13.2. The DNM2 gene, which maps to this region, was considered a good candidate. Sequencing of exons and intron-exon boundaries in the probands of 3 families identified heterozygous mutations. Two were located in exon 8 and involved the same arg369 residue, (R369Q, 602378.0004; R369W, 602378.0005), and 1 was in exon 11 and involved an R465W mutation (602378.0006). Another mutation, E368K (602378.0007), was a de novo mutation in 1 family. </p><p>Tosch et al. (2006) described a patient with centronuclear myopathy who carried heterozygous mutations in both the DNM2 (E368K; 602378.0007) and MTMR14 (Y462C; 611089.0002) genes. They noted that whereas centronuclear myopathy patients with other characterized mutations in DYN2 usually have an age of onset in childhood or adulthood, the age of onset in their patient was neonatal. The report raised the possibility of MTMR14 being a modifier of the phenotype in some cases of centronuclear myopathy. </p><p>Bitoun et al. (2007) identified 4 different de novo heterozygous DNM2 mutations (see, e.g., 602378.0010; 602378.0011) in 5 unrelated patients with sporadic CNM. All mutations were in exon 16 of the DNM2 gene within the pleckstrin homology domain. Three of the patients had a severe disorder with onset at birth. </p><p>Using in vitro sedimentation assays, Wang et al. (2010) showed that centronuclear myopathy-associated mutant DNM2 proteins (see, e.g., 602378.0005-602378.0007) formed more stable dynamin polymers in the presence of GTP compared to wildtype, presumably reflecting abnormally strong dynamin-dynamin interactions. The mutant protein aggregates were less sensitive to disassociation by GTP, and retained higher GTPase activities compared to wildtype. The observations suggested that the affected residues, such as glu368, arg369, and arg465, normally function to prevent excessive or prolonged dynamin assembly. </p><p><strong><em>Lethal Congenital Contracture Syndrome 5</em></strong></p><p>
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In 3 sibs, born of consanguineous Pakistani parents, with lethal congenital contracture syndrome-5 (LCCS5; 615368), Koutsopoulos et al. (2013) identified a homozygous missense mutation in the DNM2 gene (F379V; 602378.0013). The infants all showed severe hypotonia with lack of spontaneous movement and respiratory insufficiency at birth, resulting in death in a few days to months. Each also showed retinal hemorrhages. Studies on patient cells and in vitro functional analysis indicated that the mutation was hypomorphic. Animal studies in mice and zebrafish suggested a role for Dnm2 in the development of muscle fibers and vasculature. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>By homologous recombination, Durieux et al. (2010) developed a line of mice expressing human DNM2 with the R465W substitution (602378.0006). The vast majority of homozygous mutants died during the first hours of life. Homozygous mutant muscle fibers showed multiple structural abnormalities, disorganized intermyofibrillar networks, and loss of oxidative enzyme activity. Homozygous mutant embryonic fibroblasts showed impaired clathrin-mediated endocytosis. Heterozygous R465W mice showed normal development and locomotor activity and lived as long as wildtype littermates. However, they developed atrophy of the tibialis anterior muscle at 2 months, concomitant with impaired contractile properties and development of muscle weakness, and atrophy progressed to other muscles at 8 months. DNM2-R465W protein was expressed at wildtype levels and showed normal transversal striated pattern along the I band and expression in several other muscle regions, including sarcoplasm, perinuclear region, and postsynaptic region of the neuromuscular junction. Histopathologic abnormalities mainly affected mitochondria and reticular networks. Heterozygous R465W fibers also showed increased calcium concentration and intracellular Dnm2 and dysferlin (DYSF; 603009) accumulation. A similar accumulation of DYSF was found in biopsies from centronuclear myopathy patients with mutations in the DNM2 gene. </p><p>Koutsopoulos et al. (2013) found that morpholino knockdown of Dnm2 in zebrafish embryos resulted in lethality in 10% and bent tails in 20%. Morphant muscle fibers showed mild misalignment of muscle fibers; muscular innervation appeared normal. There were also defects in the endothelium of the vascular system. The findings suggested that Dnm2 has a pleiotropic role during development. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>13 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 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE B</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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DNM2, 9-BP DEL, NT1652
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<br />
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SNP: rs1568314339,
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ClinVar: RCV000689012, RCV000789091
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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 North American family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIB; 606482), Zuchner et al. (2005) found a 9-bp deletion of the 3-prime end of exon 14 of the DNM2 gene (1652_1659+1delATGAGGAGg). The mutation was predicted to result in 2 alternative mRNA products, one with a premature stop codon resulting from a shift of the open reading frame (D550fs) and the other an in-frame mRNA with a predicted deletion of 3 amino acids (D551_E553del) produced by disruption of the original 3-prime splice site and use of a newly introduced splice site with higher predicted splicing activity. </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>.0002 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE B, WITH NEUTROPENIA</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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DNM2, LYS558GLU
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<br />
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SNP: rs121909088,
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ClinVar: RCV000007700, RCV000789618, RCV003447076
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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 an Australian family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIB; 606482), Zuchner et al. (2005) found that affected individuals carried a mutation in exon 15 of the DNM2 gene, 1672A-G, resulting in the amino acid substitution lys558-to-glu (K558E). Subclinically low counts of neutrophils and, in some affected individuals, few lymphocytes, erythrocytes, and platelets cosegregated with CMT. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE B, WITH NEUTROPENIA</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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DNM2, LYS558 DEL
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<br />
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SNP: rs1599620408,
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ClinVar: RCV000789092, RCV001560332, RCV001869214, RCV002285173, RCV002397560
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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 Belgian family with dominant intermediate Charcot-Marie-Tooth disease and associated neutropenia (CMTDIB; 606482), Zuchner et al. (2005) identified a deletion of nucleotides 1672 through 1674 (1672_1674delAAG) in the DNM2 gene, resulting in deletion of a single amino acid, lys558. That an abnormality of lys558 was found in 2 families (see also 602378.0002) in which neutropenia, not a general feature of dominant intermediate Charcot-Marie-Tooth disease, cosegregated with the neuropathy implied that this residue has a function in maturation or survival of peripheral blood cells. Congenital neutropenia (202700) is caused by mutations in the gene elastase-2 gene (ELA2; 130130), which maps to 19p13.3. In the Belgian family, Zuchner et al. (2005) excluded mutations in ELA2 as the cause of neutropenia by sequence analysis of all coding exons. </p><p>In a follow-up of the Belgian family reported by Zuchner et al. (2005), Claeys et al. (2009) found that 1 mutation carrier had neutropenia and cataracts without signs of a neuropathy. In addition, 5 members of this family had early-onset cataracts in their teenage years. </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, CENTRONUCLEAR, 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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DNM2, ARG369GLN
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<br />
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SNP: rs121909089,
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ClinVar: RCV000007702, RCV000145900, RCV000701394, RCV001781202
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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 14 members of a family from French Guyana with autosomal dominant centronuclear myopathy (CNM1; 160150), Bitoun et al. (2005) identified a heterozygous 1106G-A mutation in exon 8 of the DNM2 gene, resulting in an arg369-to-gln (R369Q) 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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 MYOPATHY, CENTRONUCLEAR, 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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DNM2, ARG369TRP
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<br />
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|
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SNP: rs121909090,
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gnomAD: rs121909090,
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ClinVar: RCV000007703, RCV000145899, RCV000641108, RCV001027496, RCV001537068
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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 affected members of a French family with autosomal dominant centronuclear myopathy (CNM1; 160150), Bitoun et al. (2005) identified a heterozygous 1105C-to-T transition in exon 8 of the DNM2 gene that resulted in an arg369-to-trp (R369W) 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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 MYOPATHY, CENTRONUCLEAR, 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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DNM2, ARG465TRP
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<br />
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SNP: rs121909091,
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ClinVar: RCV000007704, RCV000145902, RCV000373773, RCV000641110, RCV001813964, RCV004745149
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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 French family with autosomal dominant centronuclear myopathy (CNM1; 160150), Bitoun et al. (2005) identified a heterozygous 1393C-T transition in exon 11 of the DNM2 gene, resulting in an arg465-to-trp (R465W) substitution. This mutation was found in 5 additional families with CNM1, 2 Belgian, 1 German, 1 from Great Britain, and 1 from the United States. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0007 MYOPATHY, CENTRONUCLEAR, 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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DNM2, GLU368LYS
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<br />
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SNP: rs121909092,
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gnomAD: rs121909092,
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ClinVar: RCV000007705, RCV000145898, RCV000554046, RCV000626717, RCV000725988, RCV003914819
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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 French proband with centronuclear myopathy (CNM1; 160150), Bitoun et al. (2005) identified a heterozygous 1102G-to-A transition in exon 8 of the DNM2 gene that resulted in a glu368-to-lys (E368K) substitution. The mutation occurred de novo. </p><p>Tosch et al. (2006) reported this mutation in heterozygosity in a 36-year-old woman with centronuclear myopathy who presented with neonatal hypotonia, muscle weakness, and ophthalmoparesis. She also carried a heterozygous missense mutation in the myotubularin-related protein-14 gene (MTMR14; 611089.0002). Both mutations occurred de novo. The report raised the possibility of MTMR14 being a modifier of the phenotype in some cases of centronuclear 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">
|
|
<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M</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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DNM2, GLY533CYS
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<br />
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SNP: rs121909093,
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ClinVar: RCV000007706, RCV000789617, RCV003447077
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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 autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see 606482), Fabrizi et al. (2007) identified a heterozygous 1597G-T transversion in the DNM2 gene, resulting in a gly533-to-cys (G533C) substitution. The phenotype was milder than that reported for other CMT patients with DNM2 mutations and was more consistent with an axonal form of CMT. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0009 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M</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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DNM2, LEU566HIS
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<br />
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SNP: rs121909094,
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ClinVar: RCV000007707, RCV000789619, RCV003447078
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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 45-year-old proband of a family with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see 606482), Fabrizi et al. (2007) identified a heterozygous 1697T-A transversion in the DNM2 gene, resulting in a leu566-to-his (L566H) substitution. The phenotype was milder than that reported for other CMT patients with DNM2 mutations and was more consistent with an axonal form of CMT. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 MYOPATHY, CENTRONUCLEAR, 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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DNM2, SER619LEU
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<br />
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SNP: rs121909095,
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ClinVar: RCV000007708, RCV000145908, RCV000544279, RCV000656268, RCV000754751, RCV002504764
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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 unrelated patients with sporadic centronuclear myopathy (CNM1; 160150), Bitoun et al. (2007) identified a de novo heterozygous 1856C-T transition in exon 16 of the DNM2 gene, resulting in a ser619-to-leu (S619L) substitution within the pleckstrin homology domain. Both patients had a severe phenotype, with onset at birth necessitating ventilation and nasogastric feeding, and delayed motor development. Another unrelated patient with a milder phenotype had a different heterozygous mutation in the same codon (S619W; 602378.0011). </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>.0011 MYOPATHY, CENTRONUCLEAR, 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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DNM2, SER619TRP
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<br />
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SNP: rs121909095,
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ClinVar: RCV000007709, RCV003441708, RCV003447079
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with sporadic centronuclear myopathy (CNM1; 160150), Bitoun et al. (2007) identified a de novo heterozygous 1856C-G transversion in exon 16 of the DNM2 gene, resulting in a ser619-to-trp (S619W) substitution. Two other unrelated patients with a more severe phenotype had a different heterozygous mutation in the same codon (S619L; 602378.0010). </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>.0012 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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DNM2, GLY358ARG
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<br />
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SNP: rs267606772,
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|
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ClinVar: RCV000007710, RCV000203266, RCV000369987
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</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a mother and her 2 adult daughters with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see 606482), Gallardo et al. (2008) identified a heterozygous 1072G-A transition in exon 7 of the DNM2 gene, resulting in a gly358-to-arg (G358R) substitution in a highly conserved region in the middle domain. The patients were ages 55, 32, and 23, and motor nerve conduction velocities were 33, 46, and 50 m/s, respectively. All had progressive gait unsteadiness and foot deformities, including pes cavus and toe clawing, in the first decade of life. All had distal muscle weakness and atrophy of the lower limbs, and the mother also had hand weakness and atrophy. Ankle reflexes were absent in all 3, and all had hypoesthesia of the lower limbs. MRI studies showed fatty infiltration of the calf muscles, particularly in the anterior compartment. The fatty infiltration increased distally and was massive in the foot musculature. Muscle edema was also present in affected muscles. In a follow-up of the family reported by Gallardo et al. (2008), Claeys et al. (2009) stated that the phenotype was consistent with axonal CMT2. </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>.0013 LETHAL CONGENITAL CONTRACTURE SYNDROME 5 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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DNM2, PHE379VAL
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<br />
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|
|
SNP: rs397514735,
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|
|
|
|
|
|
|
ClinVar: RCV000054501, RCV003447110
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs, born of consanguineous Pakistani parents, with lethal congenital contracture syndrome-5 (LCCS5; 615368), Koutsopoulos et al. (2013) identified a homozygous c.1135T-G transversion in exon 9 of the DNM2 gene, resulting in a phe379-to-val (F379V) substitution at a highly conserved residue in the middle domain of the protein. The mutation, which was found by homozygosity mapping followed by candidate gene sequencing, was not present in 100 Pakistani controls and was absent from SNP databases. Patient fibroblasts showed a 20% reduction in DNM2-dependent endocytosis, and recombinant F379V DNM2 showed a 20% reduction in GTPase activity, consistent with its being a hypomorphic allele. The patients showed decreased fetal movements and severe hypotonia with respiratory insufficiency at birth. They had areflexia, lack of spontaneous movement, joint contractures, and thin ribs and bones. In addition, all had retinal hemorrhages and 2 had evidence of intracranial bleeding (subdural hematoma and blood in the subarachnoid cavity). Muscle biopsy of 1 patient showed small rounded fibers with some centralized nuclei, suggestive of a congenital myopathy component, whereas muscle biopsy of another patient showed atrophic fibers without obvious centralization of nuclei. EMG studies of 1 patient suggested a myopathy or lower motor neuron disease, whereas in the other 2 patients, EMG revealed low nerve conduction velocities, suggesting a hypomyelinating neuropathy or anterior horn disease. Death occurred at ages 5 days, 19 days, and 4 months. Both parents showed decreased reflexes on examination, and skeletal muscle biopsy of the mother showed fiber size variation and centralized nuclei, suggestive of a mild form of centronuclear myopathy. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
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|
<div>
|
|
<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Bitoun, M., Bevilacqua, J. A., Prudhon, B., Maugenre, S., Taratuto, A. L., Monges, S., Lubieniecki, F., Cances, C., Uro-Coste, E., Mayer, M., Fardeau, M., Romero, N. B., Guicheney, P.
|
|
<strong>Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.</strong>
|
|
Ann. Neurol. 62: 666-670, 2007.
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[PubMed: 17932957]
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[Full Text: https://doi.org/10.1002/ana.21235]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X., Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H., Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P.
|
|
<strong>Mutations in dynamin 2 cause dominant centronuclear myopathy.</strong>
|
|
Nature Genet. 37: 1207-1209, 2005.
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[PubMed: 16227997]
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[Full Text: https://doi.org/10.1038/ng1657]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Claeys, K. G., Zuchner, S., Kennerson, M., Berciano, J., Garcia, A., Verhoeven, K., Storey, E., Merory, J. R., Bienfait, H. M. E., Lammens, M., Nelis, E., Baets, J., De Vriendt, E., Berneman, Z. N., De Veuster, I., Vance, J. M., Nicholson, G., Timmerman, V., De Jonghe, P.
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|
<strong>Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.</strong>
|
|
Brain 132: 1741-1752, 2009.
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[PubMed: 19502294]
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[Full Text: https://doi.org/10.1093/brain/awp115]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Diatloff-Zito, C., Gordon, A. J. E., Duchaud, E., Merlin, G.
|
|
<strong>Isolation of an ubiquitously expressed cDNA encoding human dynamin II, a member of the large GTP-binding protein family.</strong>
|
|
Gene 163: 301-306, 1995.
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[PubMed: 7590285]
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[Full Text: https://doi.org/10.1016/0378-1119(95)00275-b]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Durieux, A.-C., Vignaud, A., Prudhon, B., Viou, M. T., Beuvin, M., Vassilopoulos, S., Fraysse, B., Ferry, A., Laine, J., Romero, N. B., Guicheney, P., Bitoun, M.
|
|
<strong>A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.</strong>
|
|
Hum. Molec. Genet. 19: 4820-4836, 2010.
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[PubMed: 20858595]
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[Full Text: https://doi.org/10.1093/hmg/ddq413]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Fabrizi, G. M., Ferrarini, M., Cavallaro, T., Cabrini, I., Cerini, R., Bertolasi, L., Rizzuto, N.
|
|
<strong>Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.</strong>
|
|
Neurology 69: 291-295, 2007.
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|
|
[PubMed: 17636067]
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|
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[Full Text: https://doi.org/10.1212/01.wnl.0000265820.51075.61]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Gallardo, E., Claeys, K. G., Nelis, E., Garcia, A., Canga, A., Combarros, O., Timmerman, V., De Jonghe, P., Berciano, J.
|
|
<strong>Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation.</strong>
|
|
J. Neurol. 255: 986-992, 2008.
|
|
|
|
|
|
[PubMed: 18560793]
|
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|
|
[Full Text: https://doi.org/10.1007/s00415-008-0808-8]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Gomez, T. S., Hamann, M. J., McCarney, S., Savoy, D. N., Lubking, C. M., Heldebrant, M. P., Labno, C. M., McKean, D. J., McNiven, M. A., Burkhardt, J. K., Billadeau, D. D.
|
|
<strong>Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.</strong>
|
|
Nature Immun. 6: 261-270, 2005.
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|
|
[PubMed: 15696170]
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[Full Text: https://doi.org/10.1038/ni1168]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Klocke, R., Augustin, A., Ronsiek, M., Stief, A., van der Putten, H., Jockusch, H.
|
|
<strong>Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively.</strong>
|
|
Genomics 41: 290-292, 1997.
|
|
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|
|
[PubMed: 9143510]
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|
|
[Full Text: https://doi.org/10.1006/geno.1997.4634]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J.
|
|
<strong>Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.</strong>
|
|
Europ. J. Hum. Genet. 21: 637-642, 2013.
|
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|
|
|
[PubMed: 23092955]
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|
|
[Full Text: https://doi.org/10.1038/ejhg.2012.226]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Lee, J. E., Westrate, L. M., Wu, H., Page, C., Voeltz, G. K.
|
|
<strong>Multiple dynamin family members collaborate to drive mitochondrial division.</strong>
|
|
Nature 540: 139-143, 2016.
|
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|
|
|
|
[PubMed: 27798601]
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|
|
[Full Text: https://doi.org/10.1038/nature20555]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Orth, J. D., McNiven, M. A.
|
|
<strong>Dynamin at the actin-membrane interface.</strong>
|
|
Curr. Opin. Cell Biol. 15: 31-39, 2003.
|
|
|
|
|
|
[PubMed: 12517701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0955-0674(02)00010-8]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Sever, S., Altintas, M. M., Nankoe, S. R., Moller, C. C., Ko, D., Wei, C., Henderson, J., del Re, E. C., Hsing, L., Erickson, A., Cohen, C. D., Kretzler, M., Kerjaschki, D., Rudensky, A., Nikolic, B., Reiser, J.
|
|
<strong>Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.</strong>
|
|
J. Clin. Invest. 117: 2095-2104, 2007.
|
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|
|
[PubMed: 17671649]
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[Full Text: https://doi.org/10.1172/JCI32022]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Tosch, V., Rohde, H. M., Tronchere, H., Zanoteli, E., Monroy, N., Kretz, C., Dondaine, N., Payrastre, B., Mandel, J.-L., Laporte, J.
|
|
<strong>A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.</strong>
|
|
Hum. Molec. Genet. 15: 3098-3106, 2006.
|
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[PubMed: 17008356]
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[Full Text: https://doi.org/10.1093/hmg/ddl250]
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Wang, L., Barylko, B., Byers, C., Ross, J. A., Jameson, D. M., Albanesi, J. P.
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<strong>Dynamin 2 mutants linked to centronuclear myopathies form abnormally stable polymers.</strong>
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[PubMed: 20529869]
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[Full Text: https://doi.org/10.1074/jbc.C110.130013]
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Zuchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., Vance, J. M.
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<strong>Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease.</strong>
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[PubMed: 15731758]
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[Full Text: https://doi.org/10.1038/ng1514]
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Ada Hamosh - updated : 10/02/2019<br>Patricia A. Hartz - updated : 1/15/2014<br>Cassandra L. Kniffin - updated : 8/13/2013<br>Cassandra L. Kniffin - updated : 10/1/2010<br>Cassandra L. Kniffin - updated : 3/1/2010<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Cassandra L. Kniffin - updated : 1/15/2008<br>Marla J. F. O'Neill - updated : 12/21/2007<br>Patricia A. Hartz - updated : 8/22/2007<br>George E. Tiller - updated : 7/19/2007<br>Paul J. Converse - updated : 5/2/2006<br>Victor A. McKusick - updated : 11/1/2005<br>Victor A. McKusick - updated : 2/4/2005
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