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Entry
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- #602668 - MYOTONIC DYSTROPHY 2; DM2
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- OMIM
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<p>
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<span class="h4">#602668</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/602668"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS160900"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#populationGenetics">Population Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#nomenclature">Nomenclature</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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 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=" 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 id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in 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://clinicaltrials.gov/search?cond=MYOTONIC DYSTROPHY" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=545&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1466/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5079" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/myotonic-dystrophy" 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=602668[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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=606" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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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/disease/DOID:0050759" 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="http://www.informatics.jax.org/disease/602668" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0050759" 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': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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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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</a>
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</span>
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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:602668" 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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<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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</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> 715317001<br />
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<strong>ICD10CM:</strong> G71.11<br />
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<strong>ORPHA:</strong> 606<br />
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<strong>DO:</strong> 0050759<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="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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602668
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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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MYOTONIC DYSTROPHY 2; DM2
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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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DYSTROPHIA MYOTONICA 2<br />
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PROXIMAL MYOTONIC MYOPATHY; PROMM<br />
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MYOTONIC MYOPATHY, PROXIMAL<br />
|
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RICKER SYNDROME
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover 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>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/658?start=-3&limit=10&highlight=658">
|
|
3q21.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myotonic dystrophy 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602668"> 602668 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CNBP
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/116955"> 116955 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/602668" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS160900" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/602668" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/602668" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<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>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cataracts, posterior, subcapsular, iridescent <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864573&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864573</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007889" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007889</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007889" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007889</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cardiac conduction abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842820&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842820</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031546</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031546</a>]</span><br /> -
|
|
Palpitations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80313002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80313002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R00.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R00.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/785.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">785.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030252&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030252</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001962" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001962</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001962" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001962</a>]</span><br /> -
|
|
Tachycardia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86651002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86651002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3424008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3424008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R00.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/785.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">785.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3827868&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3827868</a>, <a href="https://bioportal.bioontology.org/search?q=C0039231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001649" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001649</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001649" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001649</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GENITOURINARY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Internal Genitalia (Male) </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypogonadism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48130008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48130008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020619&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020619</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000135" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000135</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000135" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000135</a>]</span><br /> -
|
|
Oligospermia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88311004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88311004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N46.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N46.11</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N46.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N46.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/606.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">606.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0868910&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0868910</a>, <a href="https://bioportal.bioontology.org/search?q=C0028960&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028960</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000798" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000798</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000798" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000798</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hyperhydrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312230002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312230002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020458&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020458</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000975" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000975</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Hair </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Frontal balding (male pattern baldness) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864584</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002292" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002292</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002292" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002292</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=8aaeb3c0ca901c9b70df7f338856c0a0" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Frontal_Balding-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=8aaeb3c0ca901c9b70df7f338856c0a0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Muscle pain <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68962001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68962001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M79.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M79.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231528&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231528</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003326</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003326</a>]</span><br /> -
|
|
Myotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3434004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3434004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700153&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700153</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002486</a>]</span><br /> -
|
|
Proximal muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249939004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221629</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span><br /> -
|
|
Deep finger muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864574&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864574</a>]</span><br /> -
|
|
Neck flexor weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843637&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843637</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003722" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003722</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003722" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003722</a>]</span><br /> -
|
|
Myotonia seen on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551445&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551445</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3434004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3434004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002486</a>]</span><br /> -
|
|
Centrally located nuclei seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551446</a>]</span><br /> -
|
|
Angulated atrophic muscle fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864578</a>]</span><br /> -
|
|
Nuclear clumps <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864579&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864579</a>]</span><br /> -
|
|
Type 2 fiber atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864580&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864580</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003554" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003554</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003554" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003554</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- No mental retardation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864572</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Insulin insensitivity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864570&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864570</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008189" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008189</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008189" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008189</a>]</span><br /> -
|
|
Low testosterone <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/131078003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">131078003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1295654&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1295654</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040171" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040171</a>]</span><br /> -
|
|
Elevated follicle stimulating hormone (FSH) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864571&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864571</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008232" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008232</a>]</span><br /> -
|
|
Diabetes mellitus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/73211009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">73211009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E08-E13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E08-E13</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">250</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011849&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011849</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000819</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000819</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> IMMUNOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Decreased serum IgG and IgM <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864582&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864582</a>]</span><br /> -
|
|
Decreased absolute lymphocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1699631&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1699631</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Elevated serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241005&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241005</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span><br /> -
|
|
Elevated gamma-glutamyltransferase (GGT) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864581&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864581</a>]</span><br /> -
|
|
Increased cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276464</a>]</span><br /> -
|
|
Increased lactate dehydrogenase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151754</a>]</span><br /> -
|
|
Increased ALT <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151905&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151905</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031964" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031964</a>]</span><br /> -
|
|
Decreased creatine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0860941&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0860941</a>]</span><br /> -
|
|
Decreased total protein <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0860901&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0860901</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Variable age of onset (range 13 to 67 years, median 48 years)<br /> -
|
|
No congenital form<br /> -
|
|
Pathogenic alleles contain 75-11,000 repeats<br /> -
|
|
Normal alleles contain up to 30 repeats<br /> -
|
|
Repeat tracts may expand as patient ages (somatic instability)<br /> -
|
|
Smaller repeat lengths in younger generations (reverse anticipation)<br /> -
|
|
See myotonic dystonia 1 (DM1, <a href="/entry/160900">160900</a>) for a disorder with a similar phenotype<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by a (CCTG)n repeat expansion in the zinc finger protein 9 gene (ZNF9, <a href="/entry/116955#0001">116955.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
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|
|
<div class="text-right">
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Myotonic dystrophy
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- <a href="/phenotypicSeries/PS160900">PS160900</a>
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- 2 Entries
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<a href="/geneMap/3/658?start=-3&limit=10&highlight=658"> 3q21.3 </a>
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<a href="/entry/602668"> Myotonic dystrophy 2 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<a href="/entry/116955"> CNBP </a>
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<a href="/entry/160900"> Myotonic dystrophy 1 </a>
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<a href="/entry/605377"> DMPK </a>
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<a href="/entry/605377"> 605377 </a>
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<p>A number sign (#) is used with this entry because myotonic dystrophy-2 (DM2/PROMM) is caused by heterozygous expansion of a CCTG repeat in intron 1 of the zinc finger protein-9 gene (ZNF9; <a href="/entry/116955">116955</a>) on chromosome 3q21.</p><p>Normal ZNF9 alleles have up to 30 repeats; pathogenic alleles contain from 75 to 11,000 repeats (<a href="#32" class="mim-tip-reference" title="Todd, P. K., Paulson, H. L. <strong>RNA-mediated neurodegeneration in repeat expansion disorders.</strong> Ann. Neurol. 67: 291-300, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20373340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20373340</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20373340[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20373340">Todd and Paulson, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20373340" 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>Myotonic dystrophy (DM) is a multisystem disorder and the most common form of muscular dystrophy in adults. Individuals with DM2 have muscle pain and stiffness, progressive muscle weakness, myotonia, male hypogonadism, cardiac arrhythmias, diabetes, and early cataracts. Other features may include cognitive dysfunction, hypersomnia, tremor, and hearing loss (summary by <a href="#8" class="mim-tip-reference" title="Heatwole, C., Johnson, N., Goldberg, B., Martens, W., Moxley, R., III. <strong>Laboratory abnormalities in patients with myotonic dystrophy type 2.</strong> Arch. Neurol. 68: 1180-1184, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21911698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21911698</a>] [<a href="https://doi.org/10.1001/archneurol.2011.191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21911698">Heatwole et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21911698" 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>See also myotonic dystrophy-1 (DM1; <a href="/entry/160900">160900</a>), caused by an expanded CTG repeat in the dystrophia myotonica protein kinase gene (DMPK; <a href="/entry/605377">605377</a>) on 19q13.</p><p>Although originally reported as 2 disorders, myotonic dystrophy-2 and proximal myotonic myopathy are now referred to collectively as DM2 (<a href="#33" class="mim-tip-reference" title="Udd, B., Meola, G., Krahe, R., Thornton, C., Ranum, L., Day, J., Bassez, G., Ricker, K. <strong>Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies. 3rd Workshop, 14-16 February 2003, Naarden, The Netherlands.</strong> Neuromusc. Disord. 13: 589-596, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12921797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12921797</a>] [<a href="https://doi.org/10.1016/s0960-8966(03)00092-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12921797">Udd et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12921797" 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="#31" class="mim-tip-reference" title="Thornton, C. A., Griggs, R. C., Moxley, R. T., III. <strong>Myotonic dystrophy with no trinucleotide repeat expansion.</strong> Ann. Neurol. 35: 269-272, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8122879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8122879</a>] [<a href="https://doi.org/10.1002/ana.410350305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8122879">Thornton et al. (1994)</a> reported patients with clinical characteristics consistent with classic myotonic dystrophy, but without the CTG repeat in the DMPK gene (see also <a href="#23" class="mim-tip-reference" title="Rowland, L. P. <strong>Thornton-Griggs-Moxley disease: myotonic dystrophy type 2.</strong> Ann. Neurol. 36: 803-804, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7979231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7979231</a>] [<a href="https://doi.org/10.1002/ana.410360526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7979231">Rowland, 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8122879+7979231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Ricker, K., Koch, M. C., Lehmann-Horn, F., Pongratz, D., Otto, M., Heine, R., Moxley, R. T., III. <strong>Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts.</strong> Neurology 44: 1448-1452, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8058147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8058147</a>] [<a href="https://doi.org/10.1212/wnl.44.8.1448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8058147">Ricker et al. (1994)</a> described 15 affected individuals in 3 pedigrees showing segregation of a novel autosomal dominant disorder, termed proximal myotonic myopathy (PROMM). Affected individuals showed features of myotonia, typically appearing between the third and fourth decade of life, and mild proximal weakness, which did not appear until the fifth to seventh decade. The severity of this disease was quite variable. None of the patients had hypersomnia, gonadal atrophy, hearing deficits, gastrointestinal hypermotility, ptosis, cardiac arrhythmia, or respiratory weakness, features often present in cases of classic myotonic dystrophy-1. Muscle biopsy demonstrated a nonspecific mild myopathy with hypertrophy of type 2 fibers with variation in diameter, but no ringbinden or subsarcolemmal masses. Physiologic studies of muscle fiber bundles taken from 2 patients demonstrated long-lasting runs of repetitive action potentials which were abolished by tetrodotoxin and/or consistently diminished by increasing the potassium concentration, a finding distinct from that present in myotonic dystrophy. Chloride conductance was normal. The number of CTG repeats in the DMPK gene was normal in the proband from each of the families. Linkage analysis performed on each of the 3 kindreds gave a significant negative lod score for DM1, chloride channel-1 (CLCN1; <a href="/entry/118425">118425</a>) on chromosome 7q, and muscle sodium channel (SCN4A; <a href="/entry/603967">603967</a>) on 17q, excluding allelism with DM1, myotonia congenita, and paramyotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8058147" 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="#21" class="mim-tip-reference" title="Ricker, K., Koch, M. C., Lehmann-Horn, F., Pongratz, D., Speich, N., Reiners, K., Schneider, C., Moxley, R. T., III. <strong>Proximal myotonic myopathy: clinical features of a multisystem disorder similar to myotonic dystrophy.</strong> Arch. Neurol. 52: 25-31, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7826272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7826272</a>] [<a href="https://doi.org/10.1001/archneur.1995.00540250029009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7826272">Ricker et al. (1995)</a> reported 27 patients with proximal myotonic myopathy from 14 families. Of the 27, 21 had proximal without distal weakness of the legs. Although only 17 of them had clinical myotonia, 23 had myotonia demonstrated electromyographically. Twenty-four had cataracts, several of which were similar to those seen in DM1. Fourteen patients complained of a burning, tearing muscle pain. Muscle atrophy was not a major feature. <a href="#21" class="mim-tip-reference" title="Ricker, K., Koch, M. C., Lehmann-Horn, F., Pongratz, D., Speich, N., Reiners, K., Schneider, C., Moxley, R. T., III. <strong>Proximal myotonic myopathy: clinical features of a multisystem disorder similar to myotonic dystrophy.</strong> Arch. Neurol. 52: 25-31, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7826272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7826272</a>] [<a href="https://doi.org/10.1001/archneur.1995.00540250029009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7826272">Ricker et al. (1995)</a> concluded that PROMM is a multisystem disorder similar to DM1 with involvement of skeletal muscle, lens, and heart. However, it appeared to have a more favorable long-term prognosis inasmuch as none of these patients demonstrated late deterioration in mental status, hypersomnia, dysphagia, or other respiratory complications. Clinically, PROMM could be distinguished from myotonic dystrophy by the proximal, rather than distal, weakness and sparing of the facial muscles. <a href="#22" class="mim-tip-reference" title="Ricker, K. <strong>Myotonic dystrophy and proximal myotonic myopathy.</strong> J. Neurol. 246: 334-338, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10399862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10399862</a>] [<a href="https://doi.org/10.1007/s004150050359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10399862">Ricker (1999)</a> concluded that PROMM is a more benign disorder than DM1, and suggested that, in Germany, the frequency of PROMM may be almost equal to that of DM. <a href="#1" class="mim-tip-reference" title="Abbruzzese, C., Krahe, R., Liguori, M., Tessarolo, D., Siciliano, M. J., Ashizawa, T., Giacanelli, M. <strong>Myotonic dystrophy phenotype without expansion of (CTG)n repeat: an entity distinct from proximal myotonic myopathy (PROMM)?</strong> J. Neurol. 243: 715-721, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923304</a>] [<a href="https://doi.org/10.1007/BF00873977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923304">Abbruzzese et al. (1996)</a> reported 6 patients from 2 families with myotonic dystrophy characterized by multisystem manifestations that were indistinguishable from those seen in DM1 and PROMM, but who did not have expansions of the chromosome 19 repeat. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7826272+8923304+10399862" 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>Among 50 patients with PROMM from 10 unrelated families in Italy, <a href="#15" class="mim-tip-reference" title="Meola, G., Sansone, V., Rotondo, G., Nobile-Orazio, E., Mongini, T., Angelini, C., Toscano, A., Mancuso, M., Siciliano, G. <strong>PROMM in Italy: clinical and biomolecular findings.</strong> Acta Myol. 2: 21-26, 1998."None>Meola et al. (1998)</a> found that 38 showed autosomal dominant inheritance and the remainder were sporadic cases. Symptoms at onset included myotonia in 30 to 60% of patients, muscle pain in 30 to 50% of patients, and lower leg weakness. Cataracts identical to those found in myotonic dystrophy-1 were identified in 15 to 30% of patients. Cardiac symptoms were present in only 5 to 10% of patients and consisted mainly of cardiac arrhythmias. Linkage analysis in the families of <a href="#15" class="mim-tip-reference" title="Meola, G., Sansone, V., Rotondo, G., Nobile-Orazio, E., Mongini, T., Angelini, C., Toscano, A., Mancuso, M., Siciliano, G. <strong>PROMM in Italy: clinical and biomolecular findings.</strong> Acta Myol. 2: 21-26, 1998."None>Meola et al. (1998)</a> excluded linkage to chromosomes 19, 17, 7, and 3.</p><p><a href="#18" class="mim-tip-reference" title="Ranum, L. P. W., Rasmussen, P. F., Benzow, K. A., Koob, M. D., Day, J. W. <strong>Genetic mapping of a second myotonic dystrophy locus.</strong> Nature Genet. 19: 196-198, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620781</a>] [<a href="https://doi.org/10.1038/570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9620781">Ranum et al. (1998)</a> identified a 5-generation family with a form of myotonic dystrophy with clinical features remarkably similar to those found in classic DM1, without the chromosome 19 CTG expansion. The authors named the locus for the disorder myotonic dystrophy-2 (DM2). Clinical features included myotonia, proximal and distal limb weakness, frontal balding, polychromatic cataracts, infertility, and cardiac arrhythmias. <a href="#6" class="mim-tip-reference" title="Day, J. W., Roelofs, R., Leroy, B., Pech, I., Benzow, K., Ranum, L. P. W. <strong>Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2).</strong> Neuromusc. Disord. 9: 19-27, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10063831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10063831</a>] [<a href="https://doi.org/10.1016/s0960-8966(98)00094-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10063831">Day et al. (1999)</a> noted that the genetically distinct form of myotonic dystrophy in this 5-generation kindred shared some of the clinical features of previously reported families with proximal myotonic myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10063831+9620781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Newman, B., Meola, G., O'Donovan, D. G., Schapira, A. H. V., Kingston, H. <strong>Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy.</strong> Neuromusc. Disord. 9: 144-149, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10382907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10382907</a>] [<a href="https://doi.org/10.1016/s0960-8966(98)00118-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10382907">Newman et al. (1999)</a> reported a family in which proximal myopathy, cataracts, intermittent myotonia, and myalgia occurred in several members in an autosomal dominant pattern. The presentation was unusual in the proband and her 2 sisters, all of whom presented with myotonia during pregnancy which resolved after each delivery. Two of the sisters experienced myalgia between each pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10382907" 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="#34" class="mim-tip-reference" title="Vihola, A., Bassez, G., Meola, G., Zhang, S., Haapasalo, H., Paetau, A., Mancinelli, E., Rouche, A., Hogrel, J. Y., Laforet, P., Maisonobe, T., Pellissier, J. F., Krahe, R., Eymard, B., Udd, B. <strong>Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2.</strong> Neurology 60: 1854-1857, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12796551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12796551</a>] [<a href="https://doi.org/10.1212/01.wnl.0000065898.61358.09" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12796551">Vihola et al. (2003)</a> reported the pathologic findings in DM2. Muscle biopsies from affected patients showed myopathic changes, including increased fiber size variation and internalized nuclei. There were scattered thin, angular, atrophic fibers, with preferential type 2 fiber atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Bonsch, D., Neumann, C., Lang-Roth, R., Witte, O., Lamprecht-Dinnesen, A., Deufel, T. <strong>PROMM and deafness: exclusion of ZNF9 as the disease gene in DFNA18 suggests a polygenic origin of the PROMM/DM2 phenotype. (Letter)</strong> Clin. Genet. 63: 73-75, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519376</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.630112.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12519376">Bonsch et al. (2003)</a> discussed PROMM and DM2 as one entity characterized by myotonia, muscular dystrophy with proximal weakness, cardiac conduction defects, endocrine disorders, and cataracts. They noted that hearing loss had been described as one feature of PROMM. <a href="#5" class="mim-tip-reference" title="Day, J. W., Ricker, K., Jacobsen, J. F., Rasmussen, L. J., Dick, K. A., Kress, W., Schneider, C., Koch, M. C., Beilman, G. J., Harrison, A. R., Dalton, J. C., Ranum, L. P. W. <strong>Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum.</strong> Neurology 60: 657-664, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601109</a>] [<a href="https://doi.org/10.1212/01.wnl.0000054481.84978.f9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601109">Day et al. (2003)</a> provided a detailed review of DM2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12519376+12601109" 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="#26" class="mim-tip-reference" title="Schoser, B. G. H., Ricker, K., Schneider-Gold, C., Hengstenberg, C., Durre, J., Bultmann, B., Kress, W., Day, J. W., Ranum, L. P. W. <strong>Sudden cardiac death in myotonic dystrophy type 2.</strong> Neurology 63: 2402-2404, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15623712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15623712</a>] [<a href="https://doi.org/10.1212/01.wnl.0000147335.10783.e4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15623712">Schoser et al. (2004)</a> reported 4 DM2 patients from 3 families who died of sudden cardiac death between ages 31 and 44 years. None of the 4 had high blood pressure, diabetes, or arteriosclerosis, and all had only mild symptoms of DM2. Only 1 patient had increasing cardiac insufficiency 6 months before death. Cardiopathologic findings in 3 patients showed dilated cardiomyopathy, with conduction system fibrosis in 2 patients. Two patients had accumulation of CCUG ribonuclear inclusions in cardiomyocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15623712" 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="Maurage, C. A., Udd, B., Ruchoux, M. M., Vermersch, P., Kalimo, H., Krahe, R., Delacourte, A., Sergeant, N. <strong>Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease.</strong> Neurology 65: 1636-1638, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301494</a>] [<a href="https://doi.org/10.1212/01.wnl.0000184585.93864.4e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301494">Maurage et al. (2005)</a> identified tau (MAPT; <a href="/entry/157140">157140</a>)-positive neurofibrillary tangles (NFTs) in multiple brain regions of a patient with DM2 originally reported by <a href="#33" class="mim-tip-reference" title="Udd, B., Meola, G., Krahe, R., Thornton, C., Ranum, L., Day, J., Bassez, G., Ricker, K. <strong>Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies. 3rd Workshop, 14-16 February 2003, Naarden, The Netherlands.</strong> Neuromusc. Disord. 13: 589-596, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12921797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12921797</a>] [<a href="https://doi.org/10.1016/s0960-8966(03)00092-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12921797">Udd et al. (2003)</a>. The findings were similar to the NFTs identified in patients with DM1 who also had cognitive impairment or mental retardation. However, the patient with DM2 studied by <a href="#14" class="mim-tip-reference" title="Maurage, C. A., Udd, B., Ruchoux, M. M., Vermersch, P., Kalimo, H., Krahe, R., Delacourte, A., Sergeant, N. <strong>Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease.</strong> Neurology 65: 1636-1638, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301494</a>] [<a href="https://doi.org/10.1212/01.wnl.0000184585.93864.4e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301494">Maurage et al. (2005)</a> was mentally normal, demonstrated no cognitive decline, and died at age 71 years from a bilateral renal thrombosis. <a href="#14" class="mim-tip-reference" title="Maurage, C. A., Udd, B., Ruchoux, M. M., Vermersch, P., Kalimo, H., Krahe, R., Delacourte, A., Sergeant, N. <strong>Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease.</strong> Neurology 65: 1636-1638, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301494</a>] [<a href="https://doi.org/10.1212/01.wnl.0000184585.93864.4e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301494">Maurage et al. (2005)</a> suggested that the findings may be related to abnormal processing of tau protein isoforms similar to the mechanism observed in DM1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12921797+16301494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Rudnik-Schoneborn, S., Schneider-Gold, C., Raabe, U., Kress, W., Zerres, K., Schoser, B. G. H. <strong>Outcome and effect of pregnancy in myotonic dystrophy type 2.</strong> Neurology 66: 579-580, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505316</a>] [<a href="https://doi.org/10.1212/01.wnl.0000198227.91131.1e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16505316">Rudnik-Schoneborn et al. (2006)</a> reported the clinical details of pregnancy in 42 women with DM2 from 37 families. Nine women (21%) had the first symptoms of DM2 during pregnancy and worsening of symptoms in subsequent pregnancies. There was often a marked improvement in symptoms after delivery. Of 96 pregnancies, 13% ended as early miscarriage and 4% as late miscarriage. Women with overt DM2 symptoms in pregnancy had a high risk of preterm labor (50%) and preterm births (27%). There was no evidence of congenital DM2 in the offspring and the overall neonatal outcome was favorable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505316" 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="#8" class="mim-tip-reference" title="Heatwole, C., Johnson, N., Goldberg, B., Martens, W., Moxley, R., III. <strong>Laboratory abnormalities in patients with myotonic dystrophy type 2.</strong> Arch. Neurol. 68: 1180-1184, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21911698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21911698</a>] [<a href="https://doi.org/10.1001/archneurol.2011.191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21911698">Heatwole et al. (2011)</a> analyzed the laboratory abnormalities of 83 patients with genetically confirmed or clinically probable DM2. Among 1,442 laboratory studies performed, 10 tests showed abnormal values in more than 40% of patients. These included increased serum creatine kinase, decreased IgG, increased total cholesterol, decreased lymphocyte count, increased lactate dehydrogenase, increased ALT, decreased creatinine, increased basophils, variable glucose levels, and decreased total protein. Only 33% of patients had increased GGT. Although endocrine laboratory studies were limited, the trend suggested low testosterone and increased FSH. The findings reinforced the idea that DM2 is a multisystem disorder and provided a means for disease screening and monitoring. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21911698" 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="Moxley, R. T., III, Udd, B., Ricker, K. <strong>Proximal myotonic myopathy (PROMM) and other proximal myotonic syndromes.</strong> Neuromusc. Disord. 8: 519-520, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9829283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9829283</a>] [<a href="https://doi.org/10.1016/s0960-8966(98)00086-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9829283">Moxley et al. (1998)</a> reviewed the diagnostic criteria of PROMM that had been delineated at the 54th European Neuromuscular Center International Workshop in 1997, before the causative ZNF9 mutation had been identified. Mandatory inclusion criteria included autosomal dominant inheritance, proximal weakness, primarily in the thighs, myotonia demonstrable by EMG, cataracts identical to those seen in DM1, and a normal size of the CTG repeat in the DM1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9829283" 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>Noting that the extremely large size and somatic instability of the DM2 expansion make molecular testing and interpretation difficult, <a href="#5" class="mim-tip-reference" title="Day, J. W., Ricker, K., Jacobsen, J. F., Rasmussen, L. J., Dick, K. A., Kress, W., Schneider, C., Koch, M. C., Beilman, G. J., Harrison, A. R., Dalton, J. C., Ranum, L. P. W. <strong>Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum.</strong> Neurology 60: 657-664, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601109</a>] [<a href="https://doi.org/10.1212/01.wnl.0000054481.84978.f9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601109">Day et al. (2003)</a> developed a repeat assay that increased the molecular detection rate of DM2 to 99%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601109" 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 5-generation family with myotonic dystrophy, <a href="#18" class="mim-tip-reference" title="Ranum, L. P. W., Rasmussen, P. F., Benzow, K. A., Koob, M. D., Day, J. W. <strong>Genetic mapping of a second myotonic dystrophy locus.</strong> Nature Genet. 19: 196-198, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620781</a>] [<a href="https://doi.org/10.1038/570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9620781">Ranum et al. (1998)</a> found that the disease locus, DM2, mapped to a 10-cM region of 3q. In addition to excluding the DM1 locus on chromosome 19 in the large family reported by <a href="#18" class="mim-tip-reference" title="Ranum, L. P. W., Rasmussen, P. F., Benzow, K. A., Koob, M. D., Day, J. W. <strong>Genetic mapping of a second myotonic dystrophy locus.</strong> Nature Genet. 19: 196-198, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620781</a>] [<a href="https://doi.org/10.1038/570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9620781">Ranum et al. (1998)</a>, <a href="#6" class="mim-tip-reference" title="Day, J. W., Roelofs, R., Leroy, B., Pech, I., Benzow, K., Ranum, L. P. W. <strong>Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2).</strong> Neuromusc. Disord. 9: 19-27, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10063831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10063831</a>] [<a href="https://doi.org/10.1016/s0960-8966(98)00094-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10063831">Day et al. (1999)</a> excluded the chromosomal regions containing the genes for muscle sodium and chloride channels that are involved in other myotonic disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10063831+9620781" 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="#19" class="mim-tip-reference" title="Ricker, K., Grimm, T., Koch, M. C., Schneider, C., Kress, W., Reimers, C. D., Schulte-Mattler, W., Mueller-Myhsok, B., Toyka, K. V., Mueller, C. R. <strong>Linkage of proximal myotonic myopathy to chromosome 3q.</strong> Neurology 52: 170-171, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921867</a>] [<a href="https://doi.org/10.1212/wnl.52.1.170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921867">Ricker et al. (1999)</a> performed linkage analysis in 9 German families with PROMM using DNA markers D3S1541 and D3S1589 from the region of the locus for DM2. Two-point analysis yielded a lod score of 5.9. <a href="#19" class="mim-tip-reference" title="Ricker, K., Grimm, T., Koch, M. C., Schneider, C., Kress, W., Reimers, C. D., Schulte-Mattler, W., Mueller-Myhsok, B., Toyka, K. V., Mueller, C. R. <strong>Linkage of proximal myotonic myopathy to chromosome 3q.</strong> Neurology 52: 170-171, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921867</a>] [<a href="https://doi.org/10.1212/wnl.52.1.170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921867">Ricker et al. (1999)</a> concluded that a gene causing PROMM is located on 3q and that PROMM and DM2 are either allelic disorders or caused by closely linked genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Sun, C., Henriksen, O. A., Tranebjaerg, L. <strong>Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM.</strong> Clin. Genet. 56: 457-461, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10665666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10665666</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560609.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10665666">Sun et al. (1999)</a> reported a Norwegian PROMM family in which the proband was clinically diagnosed with myotonic dystrophy but lacked the pathognomonic (CTG)n expansion. Haplotype analysis suggested exclusion of the DM2 locus as well, perhaps indicating further genetic heterogeneity. Interestingly, all family members, affected and unaffected, were heterozygous for the arg894-to-ter (R894X) mutation in the CLCN1 gene (<a href="/entry/118425#0010">118425.0010</a>). The authors noted that <a href="#13" class="mim-tip-reference" title="Mastaglia, F. L., Harker, N., Phillips, B. A., Day, T. J., Hankey, G. J., Laing, N. G., Fabian, V., Kakulas, B. A. <strong>Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation.</strong> J. Neurol. Neurosurg. Psychiat. 64: 543-547, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9576553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9576553</a>] [<a href="https://doi.org/10.1136/jnnp.64.4.543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9576553">Mastaglia et al. (1998)</a> had reported the R894X mutation in only 1 of 2 children with PROMM, indicating that it was not the disease-causing mutation in that family: they had termed it an incidental finding. <a href="#27" class="mim-tip-reference" title="Sun, C., Henriksen, O. A., Tranebjaerg, L. <strong>Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM.</strong> Clin. Genet. 56: 457-461, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10665666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10665666</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560609.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10665666">Sun et al. (1999)</a> suggested that their findings, combined with those of <a href="#13" class="mim-tip-reference" title="Mastaglia, F. L., Harker, N., Phillips, B. A., Day, T. J., Hankey, G. J., Laing, N. G., Fabian, V., Kakulas, B. A. <strong>Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation.</strong> J. Neurol. Neurosurg. Psychiat. 64: 543-547, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9576553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9576553</a>] [<a href="https://doi.org/10.1136/jnnp.64.4.543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9576553">Mastaglia et al. (1998)</a>, likely reflected a fairly high carrier frequency in the population, and they presented preliminary data indicating an R894X allele frequency of 0.87% (4/460) in northern Scandinavia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9576553+10665666" 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="#10" class="mim-tip-reference" title="Liquori, C. L., Ricker, K., Moseley, M. L., Jacobsen, J. F., Kress, W., Naylor, S. L., Day, J. W., Ranum, L. P. W. <strong>Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9.</strong> Science 293: 864-867, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11486088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11486088</a>] [<a href="https://doi.org/10.1126/science.1062125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11486088">Liquori et al. (2001)</a> reported that DM2 is caused by a CCTG expansion located in intron 1 of the ZNF9 gene (<a href="/entry/116955#0001">116955.0001</a>). Expanded allele sizes ranged from 75 to approximately 11,000 CCTG repeats, with a mean of approximately 5,000 repeats. Expansion sizes in the blood of affected children were usually shorter than in their parents (reverse anticipation), but the authors noted that the time-dependent somatic variation of repeat size may complicate interpretation of this difference. No significant correlation between the age of onset and expansion size was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11486088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Liquori, C. L., Ikeda, Y., Weatherspoon, M., Ricker, K., Schoser, B. G. H., Dalton, J. C., Day, J. W., Ranum, L. P. W. <strong>Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract.</strong> Am. J. Hum. Genet. 73: 849-862, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14505273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14505273</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14505273[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14505273">Liquori et al. (2003)</a> and <a href="#3" class="mim-tip-reference" title="Bachinski, L. L., Udd, B., Meola, G., Sansone, V., Bassez, G., Eymard, B., Thornton, C. A., Moxley, R. T., Harper, P. S., Rogers, M. T., Jurkat-Rott, K., Lehmann-Horn, F., and 11 others. <strong>Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect.</strong> Am. J. Hum. Genet. 73: 835-848, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12970845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12970845</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12970845[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12970845">Bachinski et al. (2003)</a> provided evidence for a founder effect of the CCTG(n) expansion in European populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12970845+14505273" 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="#25" class="mim-tip-reference" title="Saito, T., Amakusa, Y., Kimura, T., Yahara, O., Aizawa, H., Ikeda, Y., Day, J. W., Ranum, L. P. W., Ohno, K., Matsuura, T. <strong>Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian families.</strong> Neurogenetics 9: 61-63, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18057971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18057971</a>] [<a href="https://doi.org/10.1007/s10048-007-0110-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18057971">Saito et al. (2008)</a> reported a Japanese woman with DM2 who had a heterozygous expanded ZNF2 CCTG allele of 3,400 repeats. Haplotype analysis showed a background distinct from that observed in European patients, indicating a different ancestral origin of the mutation in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18057971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bachinski, L. L., Czernuszewicz, T., Ramagli, L. S., Suominen, T., Shriver, M. D., Udd, B., Siciliano, M. J., Krahe, R. <strong>Premutation allele pool in myotonic dystrophy type 2.</strong> Neurology 72: 490-497, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19020295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19020295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19020295[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/10.1212/01.wnl.0000333665.01888.33" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19020295">Bachinski et al. (2009)</a> identified 3 classes of large non-DM2 repeat alleles: short interrupted alleles of up to CCTG(24) with 2 interruptions, long interrupted alleles of up to CCTG(32) with up to 4 interruptions, and uninterrupted alleles of CCTG(22-33) with lengths of 92 to 132 bp. Large non-DM2 alleles above 40 repeats were more common among African Americans (8.5%) than European Caucasians (less than 2%). Uninterrupted alleles were significantly more unstable than interrupted alleles (p = 10(-4) to 10(-7)). SNP analysis was consistent with the hypothesis that all large alleles occurred on the same haplotype as the DM2 expansion. <a href="#2" class="mim-tip-reference" title="Bachinski, L. L., Czernuszewicz, T., Ramagli, L. S., Suominen, T., Shriver, M. D., Udd, B., Siciliano, M. J., Krahe, R. <strong>Premutation allele pool in myotonic dystrophy type 2.</strong> Neurology 72: 490-497, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19020295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19020295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19020295[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/10.1212/01.wnl.0000333665.01888.33" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19020295">Bachinski et al. (2009)</a> concluded that unstable uninterrupted CCTG(22-33) alleles may represent a premutation allele pool for DM2 full mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19020295" 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="#28" class="mim-tip-reference" title="Sun, C., Van Ghelue, M., Tranebjaerg, L., Thyssen, F., Nilssen, O., Torbergsen, T. <strong>Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene.</strong> Clin. Genet. 80: 574-580, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21204798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21204798</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01616.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21204798">Sun et al. (2011)</a> reported a large 3-generation Norwegian family in which 13 individuals had DM2 confirmed by genetic analysis. Six of the 13 patients also carried a heterozygous F413C substitution in the CLCN1 gene (<a href="/entry/118425#0001">118425.0001</a>); the F413C mutation is usually associated with autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>) when present in the homozygous or compound heterozygous state. All family members, regardless of genotype, had myotonic discharges on EMG, but the discharges were more prominent in those with both mutations. Similarly, most patients reported muscle stiffness and myalgia, and but those with both mutations tended to report more stiffness than those with only the ZNF9 expansion. These findings suggested that the CLCN1 mutation may have exaggerated the myotonia phenotype in those with the ZNF9 expansion. A 64-year-old man with only the ZNF9 expansion had generalized myalgia during his entire adult life, bilateral cataracts, and cardiomyopathy with evidence of abnormal relaxation of the myocardium. He had mild action myotonia. EMG showed myopathic changes and myotonia runs consistent with DM2. His brother, who had both mutations, had myalgia and complained of stiffness and mild muscle weakness, but strength was normal. EMG and physical examination showed myotonia. All of his 5 daughters, 3 of whom carried both mutations, developed myotonia during pregnancy that persisted after delivery. The most severely affected daughter also had cold-induced stiffness in the perioral muscles. All patients had normal cognitive function. The genetic findings helped to explain the clinical variability in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21204798" 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="#12" class="mim-tip-reference" title="Mankodi, A., Urbinati, C. R., Yuan, Q.-P., Moxley, R. T., Sansone, V., Krym, M., Henderson, D., Schalling, M., Swanson, M. S., Thornton, C. A. <strong>Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2.</strong> Hum. Molec. Genet. 10: 2165-2170, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11590133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11590133</a>] [<a href="https://doi.org/10.1093/hmg/10.19.2165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11590133">Mankodi et al. (2001)</a> investigated the possibility that DM2 is caused by expansion of a CTG repeat or related sequence. Analysis of DNA by repeat expansion detection methods and RNA by ribonuclease protection did not show an expanded CTG or CUG repeat in DM2. However, hybridization of muscle sections with fluorescence-labeled CAG-repeat oligonucleotides showed nuclear foci in DM2 similar to those seen in DM1. Nuclear foci were present in 9 patients with symptomatic DM1 and 9 patients with DM2, but not in 23 disease controls or healthy subjects. The foci were not seen with CUG- or GUC-repeat probes. Foci in DM2 were distinguished from DM1 by lower stability of the probe-target duplex, suggesting that a sequence related to the DM1 CUG expansion may accumulate in the DM2 nucleus. Muscleblind proteins (see MBNL1; <a href="/entry/606516">606516</a>), which interact with expanded CUG repeats in vitro, localized to the nuclear foci in both DM1 and DM2. The authors proposed that nuclear accumulation of mutant RNA is pathogenic in DM1, a similar disease process may occur in DM2, and muscleblind may play a role in the pathogenesis of both disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11590133" 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 DM, expression of RNAs that contain expanded CUG or CCUG repeats is associated with degeneration and repetitive action potentials (myotonia) in skeletal muscle. Using skeletal muscle from a transgenic mouse model of DM, <a href="#11" class="mim-tip-reference" title="Mankodi, A., Takahashi, M. P., Jiang, H., Beck, C. L., Bowers, W. J., Moxley, R. T., Cannon, S. C., Thornton, C. A. <strong>Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.</strong> Molec. Cell 10: 35-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150905</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00563-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12150905">Mankodi et al. (2002)</a> showed that expression of expanded CUG repeats reduces the transmembrane chloride conductance to levels well below those expected to cause myotonia. The expanded CUG repeats trigger aberrant splicing of pre-mRNA for CLC1 (<a href="/entry/118425">118425</a>), the main chloride channel in muscle, resulting in loss of CLC1 protein from the surface membrane. <a href="#11" class="mim-tip-reference" title="Mankodi, A., Takahashi, M. P., Jiang, H., Beck, C. L., Bowers, W. J., Moxley, R. T., Cannon, S. C., Thornton, C. A. <strong>Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.</strong> Molec. Cell 10: 35-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150905</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00563-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12150905">Mankodi et al. (2002)</a> identified a similar defect in CLC1 splicing and expression in human DM1 and DM2. They proposed that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12150905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Fugier, C., Klein, A. F., Hammer, C., Vassilopoulos, S., Ivarsson, Y., Toussaint, A., Tosch, V., Vignaud, A., Ferry, A., Messaddeq, N., Kokunai, Y., Tsuburaya, R., and 22 others. <strong>Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. (Letter)</strong> Nature Med. 17: 720-725, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21623381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21623381</a>] [<a href="https://doi.org/10.1038/nm.2374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21623381">Fugier et al. (2011)</a> demonstrated that alternative splicing of the BIN1 gene (<a href="/entry/601248">601248</a>) was disrupted in muscle cells derived from patients with DM1 and DM2. Exon 11 of BIN1 mRNA was skipped, and the amount of skipped mRNA correlated with disease severity. This splicing misregulation was associated with sequestration of the splicing regulator MBNL1 due to pathogenic expanded CUG or CCUG repeats. Expression of BIN1 without exon 11 resulted in little or no T tubule formation in cultured muscle cells, since this splice variant lacks a phosphatidylinositol 5-phosphate-binding site necessary for membrane-tubulating activities. Skeletal muscle biopsies from patients with DM1 showed disorganized BIN1 localization and irregular T tubule networks. Promotion of the skipping of Bin1 exon 11 in mouse skeletal muscle resulted in abnormal T tubules and decreased muscle strength, although muscle integrity was maintained. There was also decreased expression of Cacna1s (<a href="/entry/114208">114208</a>), which plays a role in the excitation-contraction coupling process. The findings suggested a link between abnormal BIN1 expression and muscle weakness in myotonic dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21623381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Tang, Z. Z., Yarotskyy, V., Wei, L., Sobczak, K., Nakamori, M., Eichinger, K., Moxley, R. T., Dirksen, R. T., Thornton, C. A. <strong>Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of CaV1.1 calcium channel.</strong> Hum. Molec. Genet. 21: 1312-1324, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22140091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22140091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22140091[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/hmg/ddr568" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22140091">Tang et al. (2012)</a> observed altered splicing of the calcium channel subunit CAV1.1 (CACNA1S) in muscle of patients with DM1 and DM2 compared with normal adult muscle and muscle of patients with facioscapulohumeral muscular dystrophy (FSHD; see <a href="/entry/158900">158900</a>). A significant fraction of CAV1.1 transcripts in DM1 and DM2 muscle showed skipping of exon 29, which represents a fetal splicing pattern. Forced exclusion of exon 29 in normal mouse skeletal muscle altered channel gating properties and increased current density and peak electrically evoked calcium transient magnitude. Downregulation of Mbnl1 in mouse cardiac muscle or overexpression of Cugbp1 (<a href="/entry/601074">601074</a>) in mouse tibialis anterior muscle enhanced skipping of exon 29, suggesting that these splicing factors may be involved in the CAV1.1 splicing defect in myotonic dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22140091" 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="#29" class="mim-tip-reference" title="Suominen, T., Bachinski, L. L., Auvinen, S., Hackman, P., Baggerly, K. A., Angelini, C., Peltonen, L., Krahe, R., Udd, B. <strong>Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland.</strong> Europ. J. Hum. Genet. 19: 776-782, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21364698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21364698</a>] [<a href="https://doi.org/10.1038/ejhg.2011.23" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21364698">Suominen et al. (2011)</a> found 2 DM2 mutations among 4,508 Finnish control individuals. One of 988 Finnish patients with a neuromuscular disorder also carried a DM2 mutation, but this patient also had genetically verified tibial muscular dystrophy (TMD; <a href="/entry/600334">600334</a>), but no myotonia. The exact sizes of the expanded repeats could not be determined. Overall, the DM2 mutation frequency was estimated to be 1 in 1,830 in the general population. In addition, 1 of 93 Italian patients with proximal myopathy or increased serum creatine kinase also carried a DM2 mutation. This 49-year-old patient had waddling gait, proximal weakness, and Gowers sign, but normal serum creatine kinase. EMG showed a myopathic pattern without myotonic discharges, possibly expanding the phenotypic spectrum of DM2 or suggesting that patients with variant symptoms may not be properly diagnosed. In the same study, the frequency of DM1 mutations was estimated to be 1 in 2,760. <a href="#29" class="mim-tip-reference" title="Suominen, T., Bachinski, L. L., Auvinen, S., Hackman, P., Baggerly, K. A., Angelini, C., Peltonen, L., Krahe, R., Udd, B. <strong>Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland.</strong> Europ. J. Hum. Genet. 19: 776-782, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21364698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21364698</a>] [<a href="https://doi.org/10.1038/ejhg.2011.23" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21364698">Suominen et al. (2011)</a> stated that the estimates of DM1 and DM2 in their study were significantly higher than previously reported estimates, which they cited as 1 in 8,000 for both DM1 and DM2. They concluded that DM1 and DM2 are more frequent than previously thought. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21364698" 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>According to the Report of the 115th ENMC Workshop, the term myotonic dystrophy type 2 refers to both DM2 and PROMM, which are essentially the same disorder (<a href="#33" class="mim-tip-reference" title="Udd, B., Meola, G., Krahe, R., Thornton, C., Ranum, L., Day, J., Bassez, G., Ricker, K. <strong>Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies. 3rd Workshop, 14-16 February 2003, Naarden, The Netherlands.</strong> Neuromusc. Disord. 13: 589-596, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12921797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12921797</a>] [<a href="https://doi.org/10.1016/s0960-8966(03)00092-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12921797">Udd et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12921797" 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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Abbruzzese, C., Krahe, R., Liguori, M., Tessarolo, D., Siciliano, M. J., Ashizawa, T., Giacanelli, M.
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<strong>Myotonic dystrophy phenotype without expansion of (CTG)n repeat: an entity distinct from proximal myotonic myopathy (PROMM)?</strong>
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J. Neurol. 243: 715-721, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923304" 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/BF00873977" target="_blank">Full Text</a>]
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Bachinski, L. L., Czernuszewicz, T., Ramagli, L. S., Suominen, T., Shriver, M. D., Udd, B., Siciliano, M. J., Krahe, R.
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<strong>Premutation allele pool in myotonic dystrophy type 2.</strong>
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Neurology 72: 490-497, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19020295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19020295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19020295[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=19020295" 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.0000333665.01888.33" target="_blank">Full Text</a>]
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Bachinski, L. L., Udd, B., Meola, G., Sansone, V., Bassez, G., Eymard, B., Thornton, C. A., Moxley, R. T., Harper, P. S., Rogers, M. T., Jurkat-Rott, K., Lehmann-Horn, F., and 11 others.
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<strong>Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect.</strong>
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Am. J. Hum. Genet. 73: 835-848, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12970845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12970845</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12970845[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=12970845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/378566" target="_blank">Full Text</a>]
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Bonsch, D., Neumann, C., Lang-Roth, R., Witte, O., Lamprecht-Dinnesen, A., Deufel, T.
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<strong>PROMM and deafness: exclusion of ZNF9 as the disease gene in DFNA18 suggests a polygenic origin of the PROMM/DM2 phenotype. (Letter)</strong>
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Clin. Genet. 63: 73-75, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12519376" 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/10.1034/j.1399-0004.2003.630112.x" target="_blank">Full Text</a>]
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Day, J. W., Ricker, K., Jacobsen, J. F., Rasmussen, L. J., Dick, K. A., Kress, W., Schneider, C., Koch, M. C., Beilman, G. J., Harrison, A. R., Dalton, J. C., Ranum, L. P. W.
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<strong>Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum.</strong>
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Neurology 60: 657-664, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601109" 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.0000054481.84978.f9" target="_blank">Full Text</a>]
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Day, J. W., Roelofs, R., Leroy, B., Pech, I., Benzow, K., Ranum, L. P. W.
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<strong>Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2).</strong>
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Neuromusc. Disord. 9: 19-27, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10063831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10063831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10063831" 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/s0960-8966(98)00094-7" target="_blank">Full Text</a>]
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Fugier, C., Klein, A. F., Hammer, C., Vassilopoulos, S., Ivarsson, Y., Toussaint, A., Tosch, V., Vignaud, A., Ferry, A., Messaddeq, N., Kokunai, Y., Tsuburaya, R., and 22 others.
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<strong>Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. (Letter)</strong>
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[<a href="https://doi.org/10.1038/nm.2374" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.1062125" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000184585.93864.4e" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0960-8966(98)00086-8" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16505316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16505316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16505316" 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.0000198227.91131.1e" target="_blank">Full Text</a>]
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<a id="Saito2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Saito, T., Amakusa, Y., Kimura, T., Yahara, O., Aizawa, H., Ikeda, Y., Day, J. W., Ranum, L. P. W., Ohno, K., Matsuura, T.
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<strong>Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian families.</strong>
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Neurogenetics 9: 61-63, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18057971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18057971</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18057971" 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/s10048-007-0110-4" target="_blank">Full Text</a>]
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<a id="26" class="mim-anchor"></a>
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<a id="Schoser2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schoser, B. G. H., Ricker, K., Schneider-Gold, C., Hengstenberg, C., Durre, J., Bultmann, B., Kress, W., Day, J. W., Ranum, L. P. W.
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<strong>Sudden cardiac death in myotonic dystrophy type 2.</strong>
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Neurology 63: 2402-2404, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15623712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15623712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15623712" 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.0000147335.10783.e4" target="_blank">Full Text</a>]
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<a id="27" class="mim-anchor"></a>
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<a id="Sun1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sun, C., Henriksen, O. A., Tranebjaerg, L.
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<strong>Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM.</strong>
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Clin. Genet. 56: 457-461, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10665666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10665666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10665666" 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/10.1034/j.1399-0004.1999.560609.x" target="_blank">Full Text</a>]
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<a id="Sun2011" class="mim-anchor"></a>
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Sun, C., Van Ghelue, M., Tranebjaerg, L., Thyssen, F., Nilssen, O., Torbergsen, T.
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<strong>Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene.</strong>
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Clin. Genet. 80: 574-580, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21204798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21204798</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21204798" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2010.01616.x" target="_blank">Full Text</a>]
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Suominen, T., Bachinski, L. L., Auvinen, S., Hackman, P., Baggerly, K. A., Angelini, C., Peltonen, L., Krahe, R., Udd, B.
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<strong>Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland.</strong>
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Europ. J. Hum. Genet. 19: 776-782, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21364698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21364698</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21364698" 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.2011.23" target="_blank">Full Text</a>]
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Tang, Z. Z., Yarotskyy, V., Wei, L., Sobczak, K., Nakamori, M., Eichinger, K., Moxley, R. T., Dirksen, R. T., Thornton, C. A.
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<strong>Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of CaV1.1 calcium channel.</strong>
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Hum. Molec. Genet. 21: 1312-1324, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22140091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22140091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22140091[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=22140091" 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/ddr568" target="_blank">Full Text</a>]
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<a id="31" class="mim-anchor"></a>
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<a id="Thornton1994" class="mim-anchor"></a>
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Thornton, C. A., Griggs, R. C., Moxley, R. T., III.
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<strong>Myotonic dystrophy with no trinucleotide repeat expansion.</strong>
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Ann. Neurol. 35: 269-272, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8122879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8122879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8122879" 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.410350305" target="_blank">Full Text</a>]
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<a id="Todd2010" class="mim-anchor"></a>
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Todd, P. K., Paulson, H. L.
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<strong>RNA-mediated neurodegeneration in repeat expansion disorders.</strong>
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Ann. Neurol. 67: 291-300, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20373340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20373340</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20373340[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=20373340" 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.21948" target="_blank">Full Text</a>]
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<a id="33" class="mim-anchor"></a>
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<a id="Udd2003" class="mim-anchor"></a>
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Udd, B., Meola, G., Krahe, R., Thornton, C., Ranum, L., Day, J., Bassez, G., Ricker, K.
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<strong>Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies. 3rd Workshop, 14-16 February 2003, Naarden, The Netherlands.</strong>
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Neuromusc. Disord. 13: 589-596, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12921797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12921797</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12921797" 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/s0960-8966(03)00092-0" target="_blank">Full Text</a>]
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<a id="34" class="mim-anchor"></a>
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<a id="Vihola2003" class="mim-anchor"></a>
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<div class="">
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Vihola, A., Bassez, G., Meola, G., Zhang, S., Haapasalo, H., Paetau, A., Mancinelli, E., Rouche, A., Hogrel, J. Y., Laforet, P., Maisonobe, T., Pellissier, J. F., Krahe, R., Eymard, B., Udd, B.
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<strong>Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2.</strong>
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Neurology 60: 1854-1857, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12796551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12796551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796551" 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.0000065898.61358.09" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/30/2013
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 7/17/2013<br>Cassandra L. Kniffin - updated : 2/13/2013<br>Cassandra L. Kniffin - updated : 5/3/2012<br>Cassandra L. Kniffin - updated : 9/6/2011<br>Cassandra L. Kniffin - updated : 8/3/2010<br>Cassandra L. Kniffin - updated : 4/6/2009<br>Cassandra L. Kniffin - updated : 3/18/2008<br>Cassandra L. Kniffin - updated : 6/25/2007<br>Cassandra L. Kniffin - updated : 2/13/2007<br>Cassandra L. Kniffin - updated : 3/21/2005<br>Cassandra L. Kniffin - reorganized : 9/11/2003<br>Cassandra L. Kniffin - updated : 9/2/2003<br>Stylianos E. Antonarakis - updated : 9/10/2002<br>George E. Tiller - updated : 2/11/2002<br>Victor A. McKusick - updated : 9/4/2001<br>Ada Hamosh - updated : 8/27/2001<br>Victor A. McKusick - updated : 4/27/1999
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 5/29/1998
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 05/10/2022
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carol : 10/31/2013<br>ckniffin : 10/30/2013<br>mgross : 7/17/2013<br>carol : 4/4/2013<br>carol : 2/26/2013<br>ckniffin : 2/13/2013<br>carol : 5/4/2012<br>terry : 5/3/2012<br>ckniffin : 5/3/2012<br>carol : 9/7/2011<br>ckniffin : 9/6/2011<br>carol : 3/21/2011<br>wwang : 8/4/2010<br>ckniffin : 8/3/2010<br>wwang : 4/13/2009<br>ckniffin : 4/6/2009<br>wwang : 4/16/2008<br>ckniffin : 3/18/2008<br>wwang : 6/28/2007<br>ckniffin : 6/25/2007<br>carol : 2/23/2007<br>ckniffin : 2/13/2007<br>joanna : 5/23/2005<br>ckniffin : 3/21/2005<br>carol : 10/3/2003<br>carol : 9/11/2003<br>ckniffin : 9/2/2003<br>carol : 2/24/2003<br>tkritzer : 2/11/2003<br>mgross : 9/10/2002<br>cwells : 2/19/2002<br>cwells : 2/11/2002<br>terry : 9/4/2001<br>alopez : 8/28/2001<br>terry : 8/27/2001<br>terry : 10/31/2000<br>carol : 6/19/2000<br>alopez : 5/10/1999<br>terry : 4/27/1999<br>dholmes : 7/22/1998<br>alopez : 6/11/1998<br>alopez : 6/1/1998
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<span class="mim-font">
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<strong>#</strong> 602668
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<div>
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<h3>
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<span class="mim-font">
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MYOTONIC DYSTROPHY 2; DM2
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<em>Alternative titles; symbols</em>
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DYSTROPHIA MYOTONICA 2<br />
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PROXIMAL MYOTONIC MYOPATHY; PROMM<br />
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MYOTONIC MYOPATHY, PROXIMAL<br />
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RICKER SYNDROME
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 715317001;
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<strong>ICD10CM:</strong> G71.11;
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<strong>ORPHA:</strong> 606;
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<strong>DO:</strong> 0050759;
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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3q21.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Myotonic dystrophy 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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602668
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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CNBP
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</span>
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</td>
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<td>
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<span class="mim-font">
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116955
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because myotonic dystrophy-2 (DM2/PROMM) is caused by heterozygous expansion of a CCTG repeat in intron 1 of the zinc finger protein-9 gene (ZNF9; 116955) on chromosome 3q21.</p><p>Normal ZNF9 alleles have up to 30 repeats; pathogenic alleles contain from 75 to 11,000 repeats (Todd and Paulson, 2010). </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>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Myotonic dystrophy (DM) is a multisystem disorder and the most common form of muscular dystrophy in adults. Individuals with DM2 have muscle pain and stiffness, progressive muscle weakness, myotonia, male hypogonadism, cardiac arrhythmias, diabetes, and early cataracts. Other features may include cognitive dysfunction, hypersomnia, tremor, and hearing loss (summary by Heatwole et al., 2011). </p><p>See also myotonic dystrophy-1 (DM1; 160900), caused by an expanded CTG repeat in the dystrophia myotonica protein kinase gene (DMPK; 605377) on 19q13.</p><p>Although originally reported as 2 disorders, myotonic dystrophy-2 and proximal myotonic myopathy are now referred to collectively as DM2 (Udd et al., 2003). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</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>Thornton et al. (1994) reported patients with clinical characteristics consistent with classic myotonic dystrophy, but without the CTG repeat in the DMPK gene (see also Rowland, 1994). </p><p>Ricker et al. (1994) described 15 affected individuals in 3 pedigrees showing segregation of a novel autosomal dominant disorder, termed proximal myotonic myopathy (PROMM). Affected individuals showed features of myotonia, typically appearing between the third and fourth decade of life, and mild proximal weakness, which did not appear until the fifth to seventh decade. The severity of this disease was quite variable. None of the patients had hypersomnia, gonadal atrophy, hearing deficits, gastrointestinal hypermotility, ptosis, cardiac arrhythmia, or respiratory weakness, features often present in cases of classic myotonic dystrophy-1. Muscle biopsy demonstrated a nonspecific mild myopathy with hypertrophy of type 2 fibers with variation in diameter, but no ringbinden or subsarcolemmal masses. Physiologic studies of muscle fiber bundles taken from 2 patients demonstrated long-lasting runs of repetitive action potentials which were abolished by tetrodotoxin and/or consistently diminished by increasing the potassium concentration, a finding distinct from that present in myotonic dystrophy. Chloride conductance was normal. The number of CTG repeats in the DMPK gene was normal in the proband from each of the families. Linkage analysis performed on each of the 3 kindreds gave a significant negative lod score for DM1, chloride channel-1 (CLCN1; 118425) on chromosome 7q, and muscle sodium channel (SCN4A; 603967) on 17q, excluding allelism with DM1, myotonia congenita, and paramyotonia. </p><p>Ricker et al. (1995) reported 27 patients with proximal myotonic myopathy from 14 families. Of the 27, 21 had proximal without distal weakness of the legs. Although only 17 of them had clinical myotonia, 23 had myotonia demonstrated electromyographically. Twenty-four had cataracts, several of which were similar to those seen in DM1. Fourteen patients complained of a burning, tearing muscle pain. Muscle atrophy was not a major feature. Ricker et al. (1995) concluded that PROMM is a multisystem disorder similar to DM1 with involvement of skeletal muscle, lens, and heart. However, it appeared to have a more favorable long-term prognosis inasmuch as none of these patients demonstrated late deterioration in mental status, hypersomnia, dysphagia, or other respiratory complications. Clinically, PROMM could be distinguished from myotonic dystrophy by the proximal, rather than distal, weakness and sparing of the facial muscles. Ricker (1999) concluded that PROMM is a more benign disorder than DM1, and suggested that, in Germany, the frequency of PROMM may be almost equal to that of DM. Abbruzzese et al. (1996) reported 6 patients from 2 families with myotonic dystrophy characterized by multisystem manifestations that were indistinguishable from those seen in DM1 and PROMM, but who did not have expansions of the chromosome 19 repeat. </p><p>Among 50 patients with PROMM from 10 unrelated families in Italy, Meola et al. (1998) found that 38 showed autosomal dominant inheritance and the remainder were sporadic cases. Symptoms at onset included myotonia in 30 to 60% of patients, muscle pain in 30 to 50% of patients, and lower leg weakness. Cataracts identical to those found in myotonic dystrophy-1 were identified in 15 to 30% of patients. Cardiac symptoms were present in only 5 to 10% of patients and consisted mainly of cardiac arrhythmias. Linkage analysis in the families of Meola et al. (1998) excluded linkage to chromosomes 19, 17, 7, and 3.</p><p>Ranum et al. (1998) identified a 5-generation family with a form of myotonic dystrophy with clinical features remarkably similar to those found in classic DM1, without the chromosome 19 CTG expansion. The authors named the locus for the disorder myotonic dystrophy-2 (DM2). Clinical features included myotonia, proximal and distal limb weakness, frontal balding, polychromatic cataracts, infertility, and cardiac arrhythmias. Day et al. (1999) noted that the genetically distinct form of myotonic dystrophy in this 5-generation kindred shared some of the clinical features of previously reported families with proximal myotonic myopathy. </p><p>Newman et al. (1999) reported a family in which proximal myopathy, cataracts, intermittent myotonia, and myalgia occurred in several members in an autosomal dominant pattern. The presentation was unusual in the proband and her 2 sisters, all of whom presented with myotonia during pregnancy which resolved after each delivery. Two of the sisters experienced myalgia between each pregnancy. </p><p>Vihola et al. (2003) reported the pathologic findings in DM2. Muscle biopsies from affected patients showed myopathic changes, including increased fiber size variation and internalized nuclei. There were scattered thin, angular, atrophic fibers, with preferential type 2 fiber atrophy. </p><p>Bonsch et al. (2003) discussed PROMM and DM2 as one entity characterized by myotonia, muscular dystrophy with proximal weakness, cardiac conduction defects, endocrine disorders, and cataracts. They noted that hearing loss had been described as one feature of PROMM. Day et al. (2003) provided a detailed review of DM2. </p><p>Schoser et al. (2004) reported 4 DM2 patients from 3 families who died of sudden cardiac death between ages 31 and 44 years. None of the 4 had high blood pressure, diabetes, or arteriosclerosis, and all had only mild symptoms of DM2. Only 1 patient had increasing cardiac insufficiency 6 months before death. Cardiopathologic findings in 3 patients showed dilated cardiomyopathy, with conduction system fibrosis in 2 patients. Two patients had accumulation of CCUG ribonuclear inclusions in cardiomyocytes. </p><p>Maurage et al. (2005) identified tau (MAPT; 157140)-positive neurofibrillary tangles (NFTs) in multiple brain regions of a patient with DM2 originally reported by Udd et al. (2003). The findings were similar to the NFTs identified in patients with DM1 who also had cognitive impairment or mental retardation. However, the patient with DM2 studied by Maurage et al. (2005) was mentally normal, demonstrated no cognitive decline, and died at age 71 years from a bilateral renal thrombosis. Maurage et al. (2005) suggested that the findings may be related to abnormal processing of tau protein isoforms similar to the mechanism observed in DM1. </p><p>Rudnik-Schoneborn et al. (2006) reported the clinical details of pregnancy in 42 women with DM2 from 37 families. Nine women (21%) had the first symptoms of DM2 during pregnancy and worsening of symptoms in subsequent pregnancies. There was often a marked improvement in symptoms after delivery. Of 96 pregnancies, 13% ended as early miscarriage and 4% as late miscarriage. Women with overt DM2 symptoms in pregnancy had a high risk of preterm labor (50%) and preterm births (27%). There was no evidence of congenital DM2 in the offspring and the overall neonatal outcome was favorable. </p><p>Heatwole et al. (2011) analyzed the laboratory abnormalities of 83 patients with genetically confirmed or clinically probable DM2. Among 1,442 laboratory studies performed, 10 tests showed abnormal values in more than 40% of patients. These included increased serum creatine kinase, decreased IgG, increased total cholesterol, decreased lymphocyte count, increased lactate dehydrogenase, increased ALT, decreased creatinine, increased basophils, variable glucose levels, and decreased total protein. Only 33% of patients had increased GGT. Although endocrine laboratory studies were limited, the trend suggested low testosterone and increased FSH. The findings reinforced the idea that DM2 is a multisystem disorder and provided a means for disease screening and monitoring. </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>Diagnosis</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>Moxley et al. (1998) reviewed the diagnostic criteria of PROMM that had been delineated at the 54th European Neuromuscular Center International Workshop in 1997, before the causative ZNF9 mutation had been identified. Mandatory inclusion criteria included autosomal dominant inheritance, proximal weakness, primarily in the thighs, myotonia demonstrable by EMG, cataracts identical to those seen in DM1, and a normal size of the CTG repeat in the DM1 gene. </p><p>Noting that the extremely large size and somatic instability of the DM2 expansion make molecular testing and interpretation difficult, Day et al. (2003) developed a repeat assay that increased the molecular detection rate of DM2 to 99%. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a 5-generation family with myotonic dystrophy, Ranum et al. (1998) found that the disease locus, DM2, mapped to a 10-cM region of 3q. In addition to excluding the DM1 locus on chromosome 19 in the large family reported by Ranum et al. (1998), Day et al. (1999) excluded the chromosomal regions containing the genes for muscle sodium and chloride channels that are involved in other myotonic disorders. </p><p>Ricker et al. (1999) performed linkage analysis in 9 German families with PROMM using DNA markers D3S1541 and D3S1589 from the region of the locus for DM2. Two-point analysis yielded a lod score of 5.9. Ricker et al. (1999) concluded that a gene causing PROMM is located on 3q and that PROMM and DM2 are either allelic disorders or caused by closely linked genes. </p><p>Sun et al. (1999) reported a Norwegian PROMM family in which the proband was clinically diagnosed with myotonic dystrophy but lacked the pathognomonic (CTG)n expansion. Haplotype analysis suggested exclusion of the DM2 locus as well, perhaps indicating further genetic heterogeneity. Interestingly, all family members, affected and unaffected, were heterozygous for the arg894-to-ter (R894X) mutation in the CLCN1 gene (118425.0010). The authors noted that Mastaglia et al. (1998) had reported the R894X mutation in only 1 of 2 children with PROMM, indicating that it was not the disease-causing mutation in that family: they had termed it an incidental finding. Sun et al. (1999) suggested that their findings, combined with those of Mastaglia et al. (1998), likely reflected a fairly high carrier frequency in the population, and they presented preliminary data indicating an R894X allele frequency of 0.87% (4/460) in northern Scandinavia. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Liquori et al. (2001) reported that DM2 is caused by a CCTG expansion located in intron 1 of the ZNF9 gene (116955.0001). Expanded allele sizes ranged from 75 to approximately 11,000 CCTG repeats, with a mean of approximately 5,000 repeats. Expansion sizes in the blood of affected children were usually shorter than in their parents (reverse anticipation), but the authors noted that the time-dependent somatic variation of repeat size may complicate interpretation of this difference. No significant correlation between the age of onset and expansion size was observed. </p><p>Liquori et al. (2003) and Bachinski et al. (2003) provided evidence for a founder effect of the CCTG(n) expansion in European populations. </p><p>Saito et al. (2008) reported a Japanese woman with DM2 who had a heterozygous expanded ZNF2 CCTG allele of 3,400 repeats. Haplotype analysis showed a background distinct from that observed in European patients, indicating a different ancestral origin of the mutation in this patient. </p><p>Bachinski et al. (2009) identified 3 classes of large non-DM2 repeat alleles: short interrupted alleles of up to CCTG(24) with 2 interruptions, long interrupted alleles of up to CCTG(32) with up to 4 interruptions, and uninterrupted alleles of CCTG(22-33) with lengths of 92 to 132 bp. Large non-DM2 alleles above 40 repeats were more common among African Americans (8.5%) than European Caucasians (less than 2%). Uninterrupted alleles were significantly more unstable than interrupted alleles (p = 10(-4) to 10(-7)). SNP analysis was consistent with the hypothesis that all large alleles occurred on the same haplotype as the DM2 expansion. Bachinski et al. (2009) concluded that unstable uninterrupted CCTG(22-33) alleles may represent a premutation allele pool for DM2 full mutations. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</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>Sun et al. (2011) reported a large 3-generation Norwegian family in which 13 individuals had DM2 confirmed by genetic analysis. Six of the 13 patients also carried a heterozygous F413C substitution in the CLCN1 gene (118425.0001); the F413C mutation is usually associated with autosomal recessive myotonia congenita (255700) when present in the homozygous or compound heterozygous state. All family members, regardless of genotype, had myotonic discharges on EMG, but the discharges were more prominent in those with both mutations. Similarly, most patients reported muscle stiffness and myalgia, and but those with both mutations tended to report more stiffness than those with only the ZNF9 expansion. These findings suggested that the CLCN1 mutation may have exaggerated the myotonia phenotype in those with the ZNF9 expansion. A 64-year-old man with only the ZNF9 expansion had generalized myalgia during his entire adult life, bilateral cataracts, and cardiomyopathy with evidence of abnormal relaxation of the myocardium. He had mild action myotonia. EMG showed myopathic changes and myotonia runs consistent with DM2. His brother, who had both mutations, had myalgia and complained of stiffness and mild muscle weakness, but strength was normal. EMG and physical examination showed myotonia. All of his 5 daughters, 3 of whom carried both mutations, developed myotonia during pregnancy that persisted after delivery. The most severely affected daughter also had cold-induced stiffness in the perioral muscles. All patients had normal cognitive function. The genetic findings helped to explain the clinical variability in this family. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</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>Mankodi et al. (2001) investigated the possibility that DM2 is caused by expansion of a CTG repeat or related sequence. Analysis of DNA by repeat expansion detection methods and RNA by ribonuclease protection did not show an expanded CTG or CUG repeat in DM2. However, hybridization of muscle sections with fluorescence-labeled CAG-repeat oligonucleotides showed nuclear foci in DM2 similar to those seen in DM1. Nuclear foci were present in 9 patients with symptomatic DM1 and 9 patients with DM2, but not in 23 disease controls or healthy subjects. The foci were not seen with CUG- or GUC-repeat probes. Foci in DM2 were distinguished from DM1 by lower stability of the probe-target duplex, suggesting that a sequence related to the DM1 CUG expansion may accumulate in the DM2 nucleus. Muscleblind proteins (see MBNL1; 606516), which interact with expanded CUG repeats in vitro, localized to the nuclear foci in both DM1 and DM2. The authors proposed that nuclear accumulation of mutant RNA is pathogenic in DM1, a similar disease process may occur in DM2, and muscleblind may play a role in the pathogenesis of both disorders. </p><p>In DM, expression of RNAs that contain expanded CUG or CCUG repeats is associated with degeneration and repetitive action potentials (myotonia) in skeletal muscle. Using skeletal muscle from a transgenic mouse model of DM, Mankodi et al. (2002) showed that expression of expanded CUG repeats reduces the transmembrane chloride conductance to levels well below those expected to cause myotonia. The expanded CUG repeats trigger aberrant splicing of pre-mRNA for CLC1 (118425), the main chloride channel in muscle, resulting in loss of CLC1 protein from the surface membrane. Mankodi et al. (2002) identified a similar defect in CLC1 splicing and expression in human DM1 and DM2. They proposed that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM. </p><p>Fugier et al. (2011) demonstrated that alternative splicing of the BIN1 gene (601248) was disrupted in muscle cells derived from patients with DM1 and DM2. Exon 11 of BIN1 mRNA was skipped, and the amount of skipped mRNA correlated with disease severity. This splicing misregulation was associated with sequestration of the splicing regulator MBNL1 due to pathogenic expanded CUG or CCUG repeats. Expression of BIN1 without exon 11 resulted in little or no T tubule formation in cultured muscle cells, since this splice variant lacks a phosphatidylinositol 5-phosphate-binding site necessary for membrane-tubulating activities. Skeletal muscle biopsies from patients with DM1 showed disorganized BIN1 localization and irregular T tubule networks. Promotion of the skipping of Bin1 exon 11 in mouse skeletal muscle resulted in abnormal T tubules and decreased muscle strength, although muscle integrity was maintained. There was also decreased expression of Cacna1s (114208), which plays a role in the excitation-contraction coupling process. The findings suggested a link between abnormal BIN1 expression and muscle weakness in myotonic dystrophy. </p><p>Tang et al. (2012) observed altered splicing of the calcium channel subunit CAV1.1 (CACNA1S) in muscle of patients with DM1 and DM2 compared with normal adult muscle and muscle of patients with facioscapulohumeral muscular dystrophy (FSHD; see 158900). A significant fraction of CAV1.1 transcripts in DM1 and DM2 muscle showed skipping of exon 29, which represents a fetal splicing pattern. Forced exclusion of exon 29 in normal mouse skeletal muscle altered channel gating properties and increased current density and peak electrically evoked calcium transient magnitude. Downregulation of Mbnl1 in mouse cardiac muscle or overexpression of Cugbp1 (601074) in mouse tibialis anterior muscle enhanced skipping of exon 29, suggesting that these splicing factors may be involved in the CAV1.1 splicing defect in myotonic dystrophy. </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>Population 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>Suominen et al. (2011) found 2 DM2 mutations among 4,508 Finnish control individuals. One of 988 Finnish patients with a neuromuscular disorder also carried a DM2 mutation, but this patient also had genetically verified tibial muscular dystrophy (TMD; 600334), but no myotonia. The exact sizes of the expanded repeats could not be determined. Overall, the DM2 mutation frequency was estimated to be 1 in 1,830 in the general population. In addition, 1 of 93 Italian patients with proximal myopathy or increased serum creatine kinase also carried a DM2 mutation. This 49-year-old patient had waddling gait, proximal weakness, and Gowers sign, but normal serum creatine kinase. EMG showed a myopathic pattern without myotonic discharges, possibly expanding the phenotypic spectrum of DM2 or suggesting that patients with variant symptoms may not be properly diagnosed. In the same study, the frequency of DM1 mutations was estimated to be 1 in 2,760. Suominen et al. (2011) stated that the estimates of DM1 and DM2 in their study were significantly higher than previously reported estimates, which they cited as 1 in 8,000 for both DM1 and DM2. They concluded that DM1 and DM2 are more frequent than previously thought. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Nomenclature</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>According to the Report of the 115th ENMC Workshop, the term myotonic dystrophy type 2 refers to both DM2 and PROMM, which are essentially the same disorder (Udd et al., 2003). </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Abbruzzese, C., Krahe, R., Liguori, M., Tessarolo, D., Siciliano, M. J., Ashizawa, T., Giacanelli, M.
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Vihola, A., Bassez, G., Meola, G., Zhang, S., Haapasalo, H., Paetau, A., Mancinelli, E., Rouche, A., Hogrel, J. Y., Laforet, P., Maisonobe, T., Pellissier, J. F., Krahe, R., Eymard, B., Udd, B.
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<strong>Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2.</strong>
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Neurology 60: 1854-1857, 2003.
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[PubMed: 12796551]
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[Full Text: https://doi.org/10.1212/01.wnl.0000065898.61358.09]
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Cassandra L. Kniffin - updated : 10/30/2013<br>Patricia A. Hartz - updated : 7/17/2013<br>Cassandra L. Kniffin - updated : 2/13/2013<br>Cassandra L. Kniffin - updated : 5/3/2012<br>Cassandra L. Kniffin - updated : 9/6/2011<br>Cassandra L. Kniffin - updated : 8/3/2010<br>Cassandra L. Kniffin - updated : 4/6/2009<br>Cassandra L. Kniffin - updated : 3/18/2008<br>Cassandra L. Kniffin - updated : 6/25/2007<br>Cassandra L. Kniffin - updated : 2/13/2007<br>Cassandra L. Kniffin - updated : 3/21/2005<br>Cassandra L. Kniffin - reorganized : 9/11/2003<br>Cassandra L. Kniffin - updated : 9/2/2003<br>Stylianos E. Antonarakis - updated : 9/10/2002<br>George E. Tiller - updated : 2/11/2002<br>Victor A. McKusick - updated : 9/4/2001<br>Ada Hamosh - updated : 8/27/2001<br>Victor A. McKusick - updated : 4/27/1999
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Victor A. McKusick : 5/29/1998
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carol : 05/10/2022<br>carol : 10/31/2013<br>ckniffin : 10/30/2013<br>mgross : 7/17/2013<br>carol : 4/4/2013<br>carol : 2/26/2013<br>ckniffin : 2/13/2013<br>carol : 5/4/2012<br>terry : 5/3/2012<br>ckniffin : 5/3/2012<br>carol : 9/7/2011<br>ckniffin : 9/6/2011<br>carol : 3/21/2011<br>wwang : 8/4/2010<br>ckniffin : 8/3/2010<br>wwang : 4/13/2009<br>ckniffin : 4/6/2009<br>wwang : 4/16/2008<br>ckniffin : 3/18/2008<br>wwang : 6/28/2007<br>ckniffin : 6/25/2007<br>carol : 2/23/2007<br>ckniffin : 2/13/2007<br>joanna : 5/23/2005<br>ckniffin : 3/21/2005<br>carol : 10/3/2003<br>carol : 9/11/2003<br>ckniffin : 9/2/2003<br>carol : 2/24/2003<br>tkritzer : 2/11/2003<br>mgross : 9/10/2002<br>cwells : 2/19/2002<br>cwells : 2/11/2002<br>terry : 9/4/2001<br>alopez : 8/28/2001<br>terry : 8/27/2001<br>terry : 10/31/2000<br>carol : 6/19/2000<br>alopez : 5/10/1999<br>terry : 4/27/1999<br>dholmes : 7/22/1998<br>alopez : 6/11/1998<br>alopez : 6/1/1998
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