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Entry
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- #620725 - BETHLEM MYOPATHY 1B; BTHLM1B
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- OMIM
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<p>
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<span class="h4">#620725</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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<li role="presentation">
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<a href="/clinicalSynopsis/620725"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS158810"> <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="#nomenclature">Nomenclature</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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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 id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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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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<div><a href="https://clinicaltrials.gov/search?cond=BETHLEM MYOPATHY" 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=367&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/NBK1503/" 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.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=610" 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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<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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<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>ORPHA:</strong> 610<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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620725
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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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BETHLEM MYOPATHY 1B; BTHLM1B
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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="phenotypeMap" class="mim-anchor"></a>
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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 table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</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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<a href="/geneMap/21/175?start=-3&limit=10&highlight=175">
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21q22.3
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</a>
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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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Bethlem myopathy 1B
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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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<a href="/entry/620725"> 620725 </a>
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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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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COL6A2
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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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<a href="/entry/120240"> 120240 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/620725" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS158810" class="btn btn-info" role="button"> Phenotypic Series </a>
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/620725" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/620725" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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 /> -
|
|
Autosomal recessive (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
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|
</span>
|
|
</div>
|
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|
</div>
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|
</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Neck </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Neck muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000467</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000467</a>]</span><br /> -
|
|
Torticollis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70070008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70070008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M43.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M43.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/723.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">723.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000473" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000473</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000473" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000473</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
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|
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|
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|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Mildly decreased forced vital capacity (in patients with biallelic mutations) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936448&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936448</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032341" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032341</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
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|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Rigid spine (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858025&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858025</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003306" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003306</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003306" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003306</a>]</span><br /> -
|
|
Contractures of the spine extensor muscles (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936449&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936449</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Limbs </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Elbow contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/239734000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">239734000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.52</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833142&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833142</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034391" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034391</a>]</span><br /> -
|
|
Knee contractures <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.56" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.56</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837263&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837263</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034671" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034671</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034671" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034671</a>]</span><br /> -
|
|
Ankle contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/239740007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">239740007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0343148&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0343148</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034677</a>]</span><br /> -
|
|
Achilles tendon contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203076007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203076007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0410264&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0410264</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001771</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001771</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Hands </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Finger contractures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1411006&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1411006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001220</a>]</span><br /> -
|
|
Distal joint hypermobility <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850851&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850851</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0020152" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0020152</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0020152" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0020152</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Feet </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Toe contractures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1406835&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1406835</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005830</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005830</a>]</span><br /> -
|
|
Pes equinovarus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203572004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203572004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.54" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.54</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/736.71" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.71</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158489</a>, <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br /> -
|
|
Distal joint hypermobility <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850851&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850851</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0020152" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0020152</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0020152" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0020152</a>]</span><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">
|
|
|
|
- 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 /> -
|
|
Shoulder girdle muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249940002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249940002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427063&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427063</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003547" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003547</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003547" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003547</a>]</span><br /> -
|
|
Pelvic girdle muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249941003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249941003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427064&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427064</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003749" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003749</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003749" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003749</a>]</span><br /> -
|
|
Muscle cramps <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45352006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45352006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55300003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55300003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.83</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/728.85" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">728.85</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037763&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037763</a>, <a href="https://bioportal.bioontology.org/search?q=C0026821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026821</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003394</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003394</a>]</span><br /> -
|
|
Difficulty running <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/282479002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">282479002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0560346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0560346</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009046" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009046</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009046" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009046</a>]</span><br /> -
|
|
Inability to run <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854490</a>]</span><br /> -
|
|
Difficulty walking <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/719232003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">719232003</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/719.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0311394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0311394</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002355</a>]</span><br /> -
|
|
Positive Gowers sign <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298294005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298294005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0575071&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575071</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003391" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003391</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003391" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003391</a>]</span><br /> -
|
|
Weakness of the extensor muscles of the hands and feet <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936445&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936445</a>]</span><br /> -
|
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Distal muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249942005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249942005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427065&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427065</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span><br /> -
|
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Myopathic features seen on skeletal muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5830427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5830427</a>]</span><br /> -
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Variation in fiber size diameter <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936446</a>]</span><br /> -
|
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Increased internal nuclei <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836056&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836056</a>]</span><br /> -
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Dystrophic features <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3275671&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3275671</a>]</span><br /> -
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Necrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/6574001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">6574001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1334928&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1334928</a>, <a href="https://bioportal.bioontology.org/search?q=C0027540&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027540</a>]</span><br /> -
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Fiber splitting <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836057&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836057</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003555" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003555</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003555" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003555</a>]</span><br /> -
|
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Increased connective tissue <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866021&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866021</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009025</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009025</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Central Nervous System </em>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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- Delayed motor development, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844429&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844429</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Peripheral Nervous System </em>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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- Mildly decreased reflexes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936447&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936447</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
|
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Normal reflexes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/102981005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">102981005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0522225&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0522225</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> LABORATORY ABNORMALITIES </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
|
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|
|
- Increased 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 />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> MISCELLANEOUS </strong>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
|
|
|
|
- Variable age at onset (infancy to adulthood)<br /> -
|
|
Slowly progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854494&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854494</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003677</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003677</a>]</span><br /> -
|
|
Most patients remain ambulatory<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> MOLECULAR BASIS </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the collagen VI, alpha-2 polypeptide gene (COL6A2, <a href="/entry/120240#0001">120240.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<h5>
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Bethlem myopathy
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- <a href="/phenotypicSeries/PS158810">PS158810</a>
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- 4 Entries
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</h5>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
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<strong>Location</strong>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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<strong>Phenotype</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Inheritance</strong>
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<strong>Phenotype<br />mapping key</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />MIM number</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Gene/Locus</strong>
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<strong>Gene/Locus<br />MIM number</strong>
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<tbody>
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<span class="mim-font">
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<a href="/geneMap/2/1149?start=-3&limit=10&highlight=1149"> 2q37.3 </a>
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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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<a href="/entry/620726"> Bethlem myopathy 1C </a>
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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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/620726"> 620726 </a>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/120250"> COL6A3 </a>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/120250"> 120250 </a>
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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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<a href="/geneMap/6/650?start=-3&limit=10&highlight=650"> 6q13-q14.1 </a>
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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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<a href="/entry/616471"> Bethlem myopathy 2 </a>
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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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/616471"> 616471 </a>
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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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<a href="/entry/120320"> COL12A1 </a>
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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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<a href="/entry/120320"> 120320 </a>
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</span>
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<span class="mim-font">
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<a href="/geneMap/21/174?start=-3&limit=10&highlight=174"> 21q22.3 </a>
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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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<a href="/entry/158810"> Bethlem myopathy 1A </a>
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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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/158810"> 158810 </a>
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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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<a href="/entry/120220"> COL6A1 </a>
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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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<a href="/entry/120220"> 120220 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/21/175?start=-3&limit=10&highlight=175"> 21q22.3 </a>
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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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<a href="/entry/620725"> Bethlem myopathy 1B </a>
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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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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<a href="/entry/620725"> 620725 </a>
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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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<a href="/entry/120240"> COL6A2 </a>
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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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<a href="/entry/120240"> 120240 </a>
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</span>
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</tbody>
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</table>
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<div class="text-right small">
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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<a id="text" class="mim-anchor"></a>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<p>A number sign (#) is used with this entry because of evidence that Bethlem myopathy-1B (BTHLM1B) is caused by heterozygous mutation in the COL6A2 gene (<a href="/entry/120240">120240</a>) on chromosome 21q22. Rare cases have been reported with homozygous or compound heterozygous mutations in the COL6A2 gene.</p><p>See also Ullrich congenital muscular dystrophy-1B (UCMD1B; <a href="/entry/620727">620727</a>), an allelic disorder with a more severe phenotype.</p>
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<br />
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<a id="description" class="mim-anchor"></a>
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<strong>Description</strong>
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<p>Bethlem myopathy-1 (BTHLM1) is a congenital muscular dystrophy characterized by proximal muscle weakness and a combination of distal and proximal flexion joint contractures. The age at onset is highly variable, ranging from infancy to adulthood, and there is intrafamilial variability. Muscle biopsy may show myopathic and dystrophic features; serum creatine kinase is elevated. The progression is slow and ambulation is usually retained into adulthood (summary by <a href="#3" class="mim-tip-reference" title="Butterfield, R. J., Foley, A. R., Dastgir, J., Asman, S., Dunn, D. M., Zou, Y., Hu, Y., Donkervoort, S., Flanigan, K. M., Swoboda, K. J., Winder, T. L., Weiss, R.B., Bonnemann, C. G. <strong>Position of glycine substitutions in the triple helix of COL6A1, COL6A2, and COL6A3 is correlated with severity and mode of inheritance in collagen VI myopathies.</strong> Hum. Mutat. 34: 1558-1567, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24038877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24038877</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24038877[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/humu.22429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24038877">Butterfield et al., 2013</a>; <a href="#10" class="mim-tip-reference" title="Scacheri, P. C., Gillanders, E. M., Subramony, S. H., Vedanarayanan, V., Crowe, C. A., Thakore, N., Bingler, M., Hoffman, E. P. <strong>Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.</strong> Neurology 58: 593-602, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11865138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11865138</a>] [<a href="https://doi.org/10.1212/wnl.58.4.593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11865138">Scacheri et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24038877+11865138" 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>For a discussion of genetic heterogeneity of Bethlem myopathy, see BTHLM1A (<a href="/entry/158810">158810</a>).</p>
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<a id="nomenclature" class="mim-anchor"></a>
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<strong>Nomenclature</strong>
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<p>At the 229th ENMC international workshop, <a href="#11" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a> reclassified Bethlem myopathy caused by mutation in one of collagen VI genes as a form of limb-girdle muscular dystrophy. Autosomal dominant forms were designated LGMDD5 (limb-girdle muscular dystrophy, autosomal dominant, 5) and autosomal recessive forms as LGMDR22 (limb-girdle muscular dystrophy, autosomal recessive, 22). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Clinical Features</strong>
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<p><a href="#1" class="mim-tip-reference" title="Arts, W. F., Bethlem, J., Volkers, W. S. <strong>Further investigations on benign myopathy with autosomal dominant inheritance.</strong> J. Neurol. 217: 201-206, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/75955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">75955</a>] [<a href="https://doi.org/10.1007/BF00312962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="75955">Arts et al. (1978)</a> described a family of Polish descent in which 6 members spanning 4 generations had a nonprogressive 'benign myopathy' with onset in infancy. Congenital torticollis was a feature in 1 patient. Clinical features included mildly delayed motor milestones with difficulty or inability to run, mild proximal muscle weakness of the head and shoulder and pelvic girdles, often with positive Gowers sign, contractures of the elbows, weakness of the extensor muscles of the fingers, feet, and toes, leading to distal flexion contractures, and mild atrophy of the affected muscles. Tendon reflexes were normal or mildly decreased. Serum creatine kinase was increased. Skeletal muscle biopsy showed marked variation in fiber size diameter and increased internal nuclei. In general, there was no progression of muscle weakness, except for deterioration after pregnancy in affected females. All remained ambulatory and many survived into old age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=75955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Scacheri, P. C., Gillanders, E. M., Subramony, S. H., Vedanarayanan, V., Crowe, C. A., Thakore, N., Bingler, M., Hoffman, E. P. <strong>Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.</strong> Neurology 58: 593-602, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11865138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11865138</a>] [<a href="https://doi.org/10.1212/wnl.58.4.593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11865138">Scacheri et al. (2002)</a> reported 9 members of a Caucasian family (family 3) from Mississippi and North Carolina with Bethlem myopathy-1B. The age at symptom onset was highly variable, ranging from infancy (1 patient) to childhood (5 patients) to adulthood (3 patients). Some showed delayed motor milestones. Features included proximal muscle weakness of the upper and lower limbs, distal muscle weakness in some, muscle cramps, flexion contractures of the elbows, knees, fingers (interphalangeal joints), and ankles. However, 4 patients did not have contractures. One adult was wheelchair-bound at 55 years of age, and another required a walking cane around 40 years of age. Muscle biopsies from 2 patients showed necrosis, fiber size variation, fiber splitting, internal nuclei, endomysial connective tissue, and fat infiltration. Serum creatine kinase was increased. The phenotype was consistent with limb-girdle muscular dystrophy. The authors noted the intrafamilial variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11865138" 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="Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong> Ann. Neurol. 62: 390-405, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>] [<a href="https://doi.org/10.1002/ana.21213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17886299">Baker et al. (2007)</a> reported 2 unrelated men (BM10 and BM273) with BTHLM1B confirmed by genetic analysis. Clinical details were limited, but both men were in their forties with proximal muscle weakness and contractures of the elbows, knees, and ankles. BM10 had limited walking ability and dystrophic changes on muscle biopsy. BM273 had normal motor capacity, but also showed weakness of the feet and hands and more extensive contractures, including of the fingers and spine extensor muscles, leading to a rigid spine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Zamurs, L. K., Idoate, M. A., Hanssen, E., Gomez-Ibanez, A., Pastor, P., Lamande, S. R. <strong>Aberrant mitochondria in a Bethlem myopathy patient with a homozygous amino acid substitution that destabilizes the collagen VI alpha2(VI) chain.</strong> J. Biol. Chem. 290: 4272-4281, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533456[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M114.632208" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533456">Zamurs et al. (2015)</a> reported a 61-year-old man (UCMD65), born of consanguineous parents, with slowly progressive proximal limb muscle weakness beginning in the first decade of life. He initially had clumsiness while playing sports or running, but could walk normally. In his thirties, he developed gait difficulties and genu valgus deformities. At age 40, he showed proximal muscle weakness and atrophy of the upper limbs, and by age 60, he needed a walker for assistance. Additional features included joint contractures of the upper and lower limb joints, dysphagia, limb muscle weakness and atrophy, and absent deep tendon reflexes. MRI showed muscle atrophy with fatty infiltration predominantly in the proximal limb muscles. Muscle biopsy showed some mitochondrial abnormalities with paracrystalline inclusions and COX-negative fibers. Collagen VI was not detected in muscle biopsy. The clinical features suggested Bethlem myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533456" 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="Caria, F., Cescon, M., Gualandi, F., Pichiecchio, A., Rossi, R., Rimessi, P., Cotti Piccinelli, S., Gallo Cassarino, S., Gregorio, I., Galvagni, A., Ferlini, A., Padovani, A., Bonaldo, P., Filosto, M. <strong>Autosomal recessive Bethlem myopathy: A clinical, genetic and functional study.</strong> Neuromusc. Disord. 29: 657-663, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31471117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31471117</a>] [<a href="https://doi.org/10.1016/j.nmd.2019.07.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31471117">Caria et al. (2019)</a> reported 2 sibs, born of unrelated parents, with autosomal recessive BTHLM1B. The patients, who were 40 and 23 years of age, had proximal muscle weakness since childhood. Physical examination showed waddling gait, positive Gowers sign, diffuse muscle atrophy and weakness of the upper and lower limbs, scapular winging, contractures of the elbows and Achilles tendons, and lumbar hyperlordosis. The older sib also had keratosis pilaris. Serum creatine kinase was moderately increased, and EMG studies showed a myopathic pattern. Skeletal muscle biopsies showed dystrophic changes with variability of fiber diameter, internal nuclei, atrophic fibers, and endomysial fibrosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31471117" 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>The transmission pattern of BTHLM1B in the families reported by <a href="#6" class="mim-tip-reference" title="Jobsis, G. J., Bolhuis, P. A., Boers, J. M., Baas, F., Wolterman, R. A., Hensels, G. W., de Visser, M. <strong>Genetic localization of Bethlem myopathy.</strong> Neurology 46: 779-782, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8618682/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8618682</a>] [<a href="https://doi.org/10.1212/wnl.46.3.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8618682">Jobsis et al. (1996)</a>, <a href="#10" class="mim-tip-reference" title="Scacheri, P. C., Gillanders, E. M., Subramony, S. H., Vedanarayanan, V., Crowe, C. A., Thakore, N., Bingler, M., Hoffman, E. P. <strong>Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.</strong> Neurology 58: 593-602, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11865138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11865138</a>] [<a href="https://doi.org/10.1212/wnl.58.4.593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11865138">Scacheri et al. (2002)</a>, <a href="#8" class="mim-tip-reference" title="Lucioli, S., Giusti, B., Mercuri, E., Vanegas, O. C., Lucarini, L., Pietroni, V., Urtizberea, A., Ben Yaou, R., de Visser, M., van der Kooi, A. J., Bonnemann, C., Iannaccone, S. T., Merlini, L., Bushby, K., Muntoni, F., Bertini, E., Chu, M.-L., Pepe, G. <strong>Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy.</strong> Neurology 64: 1931-1937, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15955946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15955946</a>] [<a href="https://doi.org/10.1212/01.WNL.0000163990.00057.66" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15955946">Lucioli et al. (2005)</a>, and <a href="#2" class="mim-tip-reference" title="Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong> Ann. Neurol. 62: 390-405, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>] [<a href="https://doi.org/10.1002/ana.21213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17886299">Baker et al. (2007)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15955946+17886299+8618682+11865138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Gualandi, F., Urciuolo, A., Martoni, E., Sabatelli, P., Squarzoni, S., Bovolenta, M., Messina, S., Mercuri, E., Franchella, A., Ferlini, A., Bonaldo, P, Merlini, L. <strong>Autosomal recessive Bethlem myopathy.</strong> Neurology 73: 1883-1891, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19949035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19949035</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181c3fd2a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19949035">Gualandi et al. (2009)</a> reported 2 unrelated patients with Bethlem myopathy who had biallelic mutations in the COL6A2 gene (<a href="/entry/120240#0011">120240.0011</a>, <a href="/entry/120240#0017">120240.0017</a>-<a href="/entry/120240#0019">120240.0019</a>), consistent with autosomal recessive inheritance. Both patients remained ambulatory as adults, and muscle biopsies and studies of fibroblasts showed variable degrees of aberrant collagen VI microfilament formation. <a href="#5" class="mim-tip-reference" title="Gualandi, F., Urciuolo, A., Martoni, E., Sabatelli, P., Squarzoni, S., Bovolenta, M., Messina, S., Mercuri, E., Franchella, A., Ferlini, A., Bonaldo, P, Merlini, L. <strong>Autosomal recessive Bethlem myopathy.</strong> Neurology 73: 1883-1891, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19949035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19949035</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181c3fd2a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19949035">Gualandi et al. (2009)</a> noted that autosomal recessive inheritance had not previously been reported in Bethlem myopathy, suggesting that collagen VI-related myopathies comprise a spectrum of conditions with variable severity. The findings in these patients did not support pure haploinsufficiency as a causative mechanism for Bethlem myopathy, and suggested that some previously reported patients may harbor a second missed mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19949035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The transmission pattern of BTHLM1B in the family reported by <a href="#4" class="mim-tip-reference" title="Caria, F., Cescon, M., Gualandi, F., Pichiecchio, A., Rossi, R., Rimessi, P., Cotti Piccinelli, S., Gallo Cassarino, S., Gregorio, I., Galvagni, A., Ferlini, A., Padovani, A., Bonaldo, P., Filosto, M. <strong>Autosomal recessive Bethlem myopathy: A clinical, genetic and functional study.</strong> Neuromusc. Disord. 29: 657-663, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31471117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31471117</a>] [<a href="https://doi.org/10.1016/j.nmd.2019.07.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31471117">Caria et al. (2019)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31471117" 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 6 Dutch families, <a href="#6" class="mim-tip-reference" title="Jobsis, G. J., Bolhuis, P. A., Boers, J. M., Baas, F., Wolterman, R. A., Hensels, G. W., de Visser, M. <strong>Genetic localization of Bethlem myopathy.</strong> Neurology 46: 779-782, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8618682/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8618682</a>] [<a href="https://doi.org/10.1212/wnl.46.3.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8618682">Jobsis et al. (1996)</a> demonstrated linkage to highly polymorphic microsatellite markers on chromosome 21q22.3. A maximum 2-point lod score of 6.86 was observed for marker PFKL with a sex averaged recombination fraction of 0.05. One recombination event was thought to exclude the collagen VI alpha-1 gene (<a href="/entry/120220">120220</a>) as a candidate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8618682" 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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In 9 families with the Bethlem form of autosomal dominant myopathy with contractures <a href="#6" class="mim-tip-reference" title="Jobsis, G. J., Bolhuis, P. A., Boers, J. M., Baas, F., Wolterman, R. A., Hensels, G. W., de Visser, M. <strong>Genetic localization of Bethlem myopathy.</strong> Neurology 46: 779-782, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8618682/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8618682</a>] [<a href="https://doi.org/10.1212/wnl.46.3.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8618682">Jobsis et al. (1996)</a> demonstrated genetic linkage to the COL6A1-COL6A2 gene cluster on 21q22.3. By sequence analysis, <a href="#7" class="mim-tip-reference" title="Jobsis, G. J., Keizers, H., Vreijling, J. P., de Visser, M., Speer, M. C., Wolterman, R. A., Baas, F., Bohlhuis, P. A. <strong>Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures.</strong> Nature Genet. 14: 113-115, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782832</a>] [<a href="https://doi.org/10.1038/ng0996-113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8782832">Jobsis et al. (1996)</a> identified a heterozygous missense mutation in the COL6A2 gene (G250S; <a href="/entry/120240#0001">120240.0001</a>) in affected members of 2 of these families (families 4 and 5; family 4 had been reported by <a href="#1" class="mim-tip-reference" title="Arts, W. F., Bethlem, J., Volkers, W. S. <strong>Further investigations on benign myopathy with autosomal dominant inheritance.</strong> J. Neurol. 217: 201-206, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/75955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">75955</a>] [<a href="https://doi.org/10.1007/BF00312962" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="75955">Arts et al., 1978</a>). The mutation disrupted the Gly-X-Y motif of the triple helical domain by substitution of gly for either val or ser. Analogous to the putative perturbation of the anchoring function of the dystrophin-associated complex in congenital muscular dystrophy with mutations in the alpha-2 subunit of laminin (<a href="/entry/156225">156225</a>), the observation suggested a similar mechanism in Bethlem myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8782832+75955+8618682" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a Caucasian family from Mississippi and North Carolina (family 3) with Bethlem myopathy, who had a limb-girdle muscular dystrophy-type phenotype, <a href="#10" class="mim-tip-reference" title="Scacheri, P. C., Gillanders, E. M., Subramony, S. H., Vedanarayanan, V., Crowe, C. A., Thakore, N., Bingler, M., Hoffman, E. P. <strong>Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.</strong> Neurology 58: 593-602, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11865138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11865138</a>] [<a href="https://doi.org/10.1212/wnl.58.4.593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11865138">Scacheri et al. (2002)</a> identified a causative heterozygous missense mutation (D620N; <a href="/entry/120240#0005">120240.0005</a>) in the COL6A2 gene. <a href="#10" class="mim-tip-reference" title="Scacheri, P. C., Gillanders, E. M., Subramony, S. H., Vedanarayanan, V., Crowe, C. A., Thakore, N., Bingler, M., Hoffman, E. P. <strong>Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.</strong> Neurology 58: 593-602, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11865138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11865138</a>] [<a href="https://doi.org/10.1212/wnl.58.4.593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11865138">Scacheri et al. (2002)</a> suggested that their studies widened the clinical spectrum of Bethlem myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11865138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated men (BM10 and BM273) with Bethlem myopathy, <a href="#2" class="mim-tip-reference" title="Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong> Ann. Neurol. 62: 390-405, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>] [<a href="https://doi.org/10.1002/ana.21213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17886299">Baker et al. (2007)</a> identified different heterozygous mutations in the COL6A2 gene (<a href="/entry/120240#0009">120240.0009</a>; <a href="/entry/120240#0010">120240.0010</a>). In vitro studies indicated defective collagen VI synthesis and secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Autosomal Recessive Bethlem Myopathy 1B</em></strong></p><p>
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In 2 patients with Bethlem myopathy-1B, <a href="#5" class="mim-tip-reference" title="Gualandi, F., Urciuolo, A., Martoni, E., Sabatelli, P., Squarzoni, S., Bovolenta, M., Messina, S., Mercuri, E., Franchella, A., Ferlini, A., Bonaldo, P, Merlini, L. <strong>Autosomal recessive Bethlem myopathy.</strong> Neurology 73: 1883-1891, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19949035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19949035</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181c3fd2a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19949035">Gualandi et al. (2009)</a> identified compound heterozygous mutations in the COL6A2 gene. One patient was a 25-year-old woman who was compound heterozygous for a Q819X (<a href="/entry/120240#0011">120240.0011</a>) mutation and a complex missense allele (R830Q/R843W; <a href="/entry/120240#0017">120240.0017</a>). Although this genotype suggested autosomal recessive inheritance, the Q819X mutation escaped nonsense-mediated decay and was thought not to be pathogenic in the heterozygous state, based on a report by <a href="#9" class="mim-tip-reference" title="Merlini, L., Martoni, E., Grumati, P., Sabatelli, P., Squarzoni, S., Urciuolo, A., Ferlini, A., Gualandi, F., Bonaldo, P. <strong>Autosomal recessive myosclerosis myopathy is a collagen VI disorder.</strong> Neurology 71: 1245-1253, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18852439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18852439</a>] [<a href="https://doi.org/10.1212/01.wnl.0000327611.01687.5e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18852439">Merlini et al. (2008)</a>; however, the fact that the woman reported by <a href="#5" class="mim-tip-reference" title="Gualandi, F., Urciuolo, A., Martoni, E., Sabatelli, P., Squarzoni, S., Bovolenta, M., Messina, S., Mercuri, E., Franchella, A., Ferlini, A., Bonaldo, P, Merlini, L. <strong>Autosomal recessive Bethlem myopathy.</strong> Neurology 73: 1883-1891, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19949035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19949035</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181c3fd2a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19949035">Gualandi et al. (2009)</a> carried COL6A2 mutations on both alleles had implications for genetic counseling. The other patient was a 47-year-old man with an R366X mutation (<a href="/entry/120240#0018">120240.0018</a>) inherited from his unaffected mother and a de novo D871N mutation (<a href="/entry/120240#0019">120240.0019</a>). The authors stated that the combination of a missense and a nonsense mutation in the COL6A2 gene had not previously been reported, yielding implications for genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19949035+18852439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 61-year-old man, born of consanguineous parents, with autosomal recessive Bethlem myopathy-1B, <a href="#12" class="mim-tip-reference" title="Zamurs, L. K., Idoate, M. A., Hanssen, E., Gomez-Ibanez, A., Pastor, P., Lamande, S. R. <strong>Aberrant mitochondria in a Bethlem myopathy patient with a homozygous amino acid substitution that destabilizes the collagen VI alpha2(VI) chain.</strong> J. Biol. Chem. 290: 4272-4281, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533456[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M114.632208" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533456">Zamurs et al. (2015)</a> identified a homozygous missense mutation in the COL6A2 gene (D871N; <a href="/entry/120240#0019">120240.0019</a>). His unaffected parents were each heterozygous for the variant. Detailed studies of patient fibroblasts showed that the mutant protein interfered with collagen VI assembly, secretion, and microfibril formation, all of which were reduced compared to controls. Some collagen VI was assembled, albeit more slowly than normal, and was secreted; these molecules contained the minor COL6A2 C2a splice form that has an alternative C terminus and does not contain the mutation. When expressed in HEK293 cells, the mutant D871N protein was retained in the endoplasmic reticulum due to abnormal protein folding and was selectively degraded by the proteosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 adult sibs with autosomal recessive Bethlem myopathy-1B, <a href="#4" class="mim-tip-reference" title="Caria, F., Cescon, M., Gualandi, F., Pichiecchio, A., Rossi, R., Rimessi, P., Cotti Piccinelli, S., Gallo Cassarino, S., Gregorio, I., Galvagni, A., Ferlini, A., Padovani, A., Bonaldo, P., Filosto, M. <strong>Autosomal recessive Bethlem myopathy: A clinical, genetic and functional study.</strong> Neuromusc. Disord. 29: 657-663, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31471117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31471117</a>] [<a href="https://doi.org/10.1016/j.nmd.2019.07.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31471117">Caria et al. (2019)</a> identified compound heterozygous mutations in the COL6A2 gene: a nonsense mutation in exon 28, resulting in a gln889-to-ter (Q889X; <a href="/entry/120240#0022">120240.0022</a>) and an in-frame insertion (<a href="/entry/120240#0023">120240.0023</a>) in exon 5. The mutations, which were found by next-generation panel sequencing and confirmed by Sanger sequencing, were each inherited from an unaffected parent. Western blot analysis of patient fibroblasts showed low levels of the canonical 1,019-residue COL6A2 chain and presence of a truncated 889-residue mutant protein; a normal 918-residue splice variant (C2a) was also detected. There were normal amounts of collagen VI dimers and tetramers in the cell layer, but not in the cell media, indicating instability of the secreted protein. Immunofluorescence studies of patient fibroblasts showed markedly reduced expression of collagen VI that was poorly organized in the extracellular matrix. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31471117" 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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Arts, W. F., Bethlem, J., Volkers, W. S.
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[<a href="https://doi.org/10.1007/BF00312962" target="_blank">Full Text</a>]
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Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R.
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<strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong>
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Ann. Neurol. 62: 390-405, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" 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.21213" target="_blank">Full Text</a>]
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Butterfield, R. J., Foley, A. R., Dastgir, J., Asman, S., Dunn, D. M., Zou, Y., Hu, Y., Donkervoort, S., Flanigan, K. M., Swoboda, K. J., Winder, T. L., Weiss, R.B., Bonnemann, C. G.
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<strong>Position of glycine substitutions in the triple helix of COL6A1, COL6A2, and COL6A3 is correlated with severity and mode of inheritance in collagen VI myopathies.</strong>
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Hum. Mutat. 34: 1558-1567, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24038877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24038877</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24038877[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=24038877" 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/humu.22429" target="_blank">Full Text</a>]
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Caria, F., Cescon, M., Gualandi, F., Pichiecchio, A., Rossi, R., Rimessi, P., Cotti Piccinelli, S., Gallo Cassarino, S., Gregorio, I., Galvagni, A., Ferlini, A., Padovani, A., Bonaldo, P., Filosto, M.
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<strong>Autosomal recessive Bethlem myopathy: A clinical, genetic and functional study.</strong>
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Neuromusc. Disord. 29: 657-663, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31471117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31471117</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31471117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Gualandi, F., Urciuolo, A., Martoni, E., Sabatelli, P., Squarzoni, S., Bovolenta, M., Messina, S., Mercuri, E., Franchella, A., Ferlini, A., Bonaldo, P, Merlini, L.
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<strong>Autosomal recessive Bethlem myopathy.</strong>
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Neurology 73: 1883-1891, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19949035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19949035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19949035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/WNL.0b013e3181c3fd2a" target="_blank">Full Text</a>]
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Jobsis, G. J., Bolhuis, P. A., Boers, J. M., Baas, F., Wolterman, R. A., Hensels, G. W., de Visser, M.
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Jobsis, G. J., Keizers, H., Vreijling, J. P., de Visser, M., Speer, M. C., Wolterman, R. A., Baas, F., Bohlhuis, P. A.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8782832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8782832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8782832" 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/ng0996-113" target="_blank">Full Text</a>]
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Lucioli, S., Giusti, B., Mercuri, E., Vanegas, O. C., Lucarini, L., Pietroni, V., Urtizberea, A., Ben Yaou, R., de Visser, M., van der Kooi, A. J., Bonnemann, C., Iannaccone, S. T., Merlini, L., Bushby, K., Muntoni, F., Bertini, E., Chu, M.-L., Pepe, G.
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<strong>Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15955946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15955946</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15955946" 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.0000163990.00057.66" target="_blank">Full Text</a>]
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Merlini, L., Martoni, E., Grumati, P., Sabatelli, P., Squarzoni, S., Urciuolo, A., Ferlini, A., Gualandi, F., Bonaldo, P.
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<strong>Autosomal recessive myosclerosis myopathy is a collagen VI disorder.</strong>
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Neurology 71: 1245-1253, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18852439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18852439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18852439" 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.0000327611.01687.5e" target="_blank">Full Text</a>]
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Scacheri, P. C., Gillanders, E. M., Subramony, S. H., Vedanarayanan, V., Crowe, C. A., Thakore, N., Bingler, M., Hoffman, E. P.
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<strong>Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.</strong>
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Neurology 58: 593-602, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11865138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11865138</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11865138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.58.4.593" target="_blank">Full Text</a>]
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<a id="Straub2018" class="mim-anchor"></a>
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Straub, V., Murphy, A., Udd, B.
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<strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong>
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Neuromusc. Disord. 28: 702-710, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank">Full Text</a>]
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<a id="Zamurs2015" class="mim-anchor"></a>
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Zamurs, L. K., Idoate, M. A., Hanssen, E., Gomez-Ibanez, A., Pastor, P., Lamande, S. R.
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<strong>Aberrant mitochondria in a Bethlem myopathy patient with a homozygous amino acid substitution that destabilizes the collagen VI alpha2(VI) chain.</strong>
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J. Biol. Chem. 290: 4272-4281, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533456[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=25533456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M114.632208" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 07/10/2024
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Cassandra L. Kniffin - updated : 07/05/2024
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Ada Hamosh : 02/19/2024
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carol : 07/15/2024
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ckniffin : 07/10/2024<br>ckniffin : 07/05/2024<br>carol : 06/06/2024<br>carol : 06/05/2024<br>ckniffin : 06/05/2024<br>carol : 04/11/2024<br>carol : 02/28/2024<br>carol : 02/22/2024<br>carol : 02/21/2024
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<strong>#</strong> 620725
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BETHLEM MYOPATHY 1B; BTHLM1B
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<strong>ORPHA:</strong> 610;
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Phenotype
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Inheritance
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21q22.3
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Bethlem myopathy 1B
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620725
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Autosomal dominant; Autosomal recessive
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COL6A2
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120240
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<p>A number sign (#) is used with this entry because of evidence that Bethlem myopathy-1B (BTHLM1B) is caused by heterozygous mutation in the COL6A2 gene (120240) on chromosome 21q22. Rare cases have been reported with homozygous or compound heterozygous mutations in the COL6A2 gene.</p><p>See also Ullrich congenital muscular dystrophy-1B (UCMD1B; 620727), an allelic disorder with a more severe phenotype.</p>
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<p>Bethlem myopathy-1 (BTHLM1) is a congenital muscular dystrophy characterized by proximal muscle weakness and a combination of distal and proximal flexion joint contractures. The age at onset is highly variable, ranging from infancy to adulthood, and there is intrafamilial variability. Muscle biopsy may show myopathic and dystrophic features; serum creatine kinase is elevated. The progression is slow and ambulation is usually retained into adulthood (summary by Butterfield et al., 2013; Scacheri et al., 2002). </p><p>For a discussion of genetic heterogeneity of Bethlem myopathy, see BTHLM1A (158810).</p>
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<p>At the 229th ENMC international workshop, Straub et al. (2018) reclassified Bethlem myopathy caused by mutation in one of collagen VI genes as a form of limb-girdle muscular dystrophy. Autosomal dominant forms were designated LGMDD5 (limb-girdle muscular dystrophy, autosomal dominant, 5) and autosomal recessive forms as LGMDR22 (limb-girdle muscular dystrophy, autosomal recessive, 22). </p>
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<p>Arts et al. (1978) described a family of Polish descent in which 6 members spanning 4 generations had a nonprogressive 'benign myopathy' with onset in infancy. Congenital torticollis was a feature in 1 patient. Clinical features included mildly delayed motor milestones with difficulty or inability to run, mild proximal muscle weakness of the head and shoulder and pelvic girdles, often with positive Gowers sign, contractures of the elbows, weakness of the extensor muscles of the fingers, feet, and toes, leading to distal flexion contractures, and mild atrophy of the affected muscles. Tendon reflexes were normal or mildly decreased. Serum creatine kinase was increased. Skeletal muscle biopsy showed marked variation in fiber size diameter and increased internal nuclei. In general, there was no progression of muscle weakness, except for deterioration after pregnancy in affected females. All remained ambulatory and many survived into old age. </p><p>Scacheri et al. (2002) reported 9 members of a Caucasian family (family 3) from Mississippi and North Carolina with Bethlem myopathy-1B. The age at symptom onset was highly variable, ranging from infancy (1 patient) to childhood (5 patients) to adulthood (3 patients). Some showed delayed motor milestones. Features included proximal muscle weakness of the upper and lower limbs, distal muscle weakness in some, muscle cramps, flexion contractures of the elbows, knees, fingers (interphalangeal joints), and ankles. However, 4 patients did not have contractures. One adult was wheelchair-bound at 55 years of age, and another required a walking cane around 40 years of age. Muscle biopsies from 2 patients showed necrosis, fiber size variation, fiber splitting, internal nuclei, endomysial connective tissue, and fat infiltration. Serum creatine kinase was increased. The phenotype was consistent with limb-girdle muscular dystrophy. The authors noted the intrafamilial variability. </p><p>Baker et al. (2007) reported 2 unrelated men (BM10 and BM273) with BTHLM1B confirmed by genetic analysis. Clinical details were limited, but both men were in their forties with proximal muscle weakness and contractures of the elbows, knees, and ankles. BM10 had limited walking ability and dystrophic changes on muscle biopsy. BM273 had normal motor capacity, but also showed weakness of the feet and hands and more extensive contractures, including of the fingers and spine extensor muscles, leading to a rigid spine. </p><p>Zamurs et al. (2015) reported a 61-year-old man (UCMD65), born of consanguineous parents, with slowly progressive proximal limb muscle weakness beginning in the first decade of life. He initially had clumsiness while playing sports or running, but could walk normally. In his thirties, he developed gait difficulties and genu valgus deformities. At age 40, he showed proximal muscle weakness and atrophy of the upper limbs, and by age 60, he needed a walker for assistance. Additional features included joint contractures of the upper and lower limb joints, dysphagia, limb muscle weakness and atrophy, and absent deep tendon reflexes. MRI showed muscle atrophy with fatty infiltration predominantly in the proximal limb muscles. Muscle biopsy showed some mitochondrial abnormalities with paracrystalline inclusions and COX-negative fibers. Collagen VI was not detected in muscle biopsy. The clinical features suggested Bethlem myopathy. </p><p>Caria et al. (2019) reported 2 sibs, born of unrelated parents, with autosomal recessive BTHLM1B. The patients, who were 40 and 23 years of age, had proximal muscle weakness since childhood. Physical examination showed waddling gait, positive Gowers sign, diffuse muscle atrophy and weakness of the upper and lower limbs, scapular winging, contractures of the elbows and Achilles tendons, and lumbar hyperlordosis. The older sib also had keratosis pilaris. Serum creatine kinase was moderately increased, and EMG studies showed a myopathic pattern. Skeletal muscle biopsies showed dystrophic changes with variability of fiber diameter, internal nuclei, atrophic fibers, and endomysial fibrosis. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of BTHLM1B in the families reported by Jobsis et al. (1996), Scacheri et al. (2002), Lucioli et al. (2005), and Baker et al. (2007) was consistent with autosomal dominant inheritance. </p><p>Gualandi et al. (2009) reported 2 unrelated patients with Bethlem myopathy who had biallelic mutations in the COL6A2 gene (120240.0011, 120240.0017-120240.0019), consistent with autosomal recessive inheritance. Both patients remained ambulatory as adults, and muscle biopsies and studies of fibroblasts showed variable degrees of aberrant collagen VI microfilament formation. Gualandi et al. (2009) noted that autosomal recessive inheritance had not previously been reported in Bethlem myopathy, suggesting that collagen VI-related myopathies comprise a spectrum of conditions with variable severity. The findings in these patients did not support pure haploinsufficiency as a causative mechanism for Bethlem myopathy, and suggested that some previously reported patients may harbor a second missed mutation. </p><p>The transmission pattern of BTHLM1B in the family reported by Caria et al. (2019) was consistent with autosomal recessive inheritance. </p>
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<strong>Mapping</strong>
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<p>In 6 Dutch families, Jobsis et al. (1996) demonstrated linkage to highly polymorphic microsatellite markers on chromosome 21q22.3. A maximum 2-point lod score of 6.86 was observed for marker PFKL with a sex averaged recombination fraction of 0.05. One recombination event was thought to exclude the collagen VI alpha-1 gene (120220) as a candidate. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Autosomal Dominant Bethlem Myopathy 1B</em></strong></p><p>
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In 9 families with the Bethlem form of autosomal dominant myopathy with contractures Jobsis et al. (1996) demonstrated genetic linkage to the COL6A1-COL6A2 gene cluster on 21q22.3. By sequence analysis, Jobsis et al. (1996) identified a heterozygous missense mutation in the COL6A2 gene (G250S; 120240.0001) in affected members of 2 of these families (families 4 and 5; family 4 had been reported by Arts et al., 1978). The mutation disrupted the Gly-X-Y motif of the triple helical domain by substitution of gly for either val or ser. Analogous to the putative perturbation of the anchoring function of the dystrophin-associated complex in congenital muscular dystrophy with mutations in the alpha-2 subunit of laminin (156225), the observation suggested a similar mechanism in Bethlem myopathy. </p><p>In affected members of a Caucasian family from Mississippi and North Carolina (family 3) with Bethlem myopathy, who had a limb-girdle muscular dystrophy-type phenotype, Scacheri et al. (2002) identified a causative heterozygous missense mutation (D620N; 120240.0005) in the COL6A2 gene. Scacheri et al. (2002) suggested that their studies widened the clinical spectrum of Bethlem myopathy. </p><p>In 2 unrelated men (BM10 and BM273) with Bethlem myopathy, Baker et al. (2007) identified different heterozygous mutations in the COL6A2 gene (120240.0009; 120240.0010). In vitro studies indicated defective collagen VI synthesis and secretion. </p><p><strong><em>Autosomal Recessive Bethlem Myopathy 1B</em></strong></p><p>
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In 2 patients with Bethlem myopathy-1B, Gualandi et al. (2009) identified compound heterozygous mutations in the COL6A2 gene. One patient was a 25-year-old woman who was compound heterozygous for a Q819X (120240.0011) mutation and a complex missense allele (R830Q/R843W; 120240.0017). Although this genotype suggested autosomal recessive inheritance, the Q819X mutation escaped nonsense-mediated decay and was thought not to be pathogenic in the heterozygous state, based on a report by Merlini et al. (2008); however, the fact that the woman reported by Gualandi et al. (2009) carried COL6A2 mutations on both alleles had implications for genetic counseling. The other patient was a 47-year-old man with an R366X mutation (120240.0018) inherited from his unaffected mother and a de novo D871N mutation (120240.0019). The authors stated that the combination of a missense and a nonsense mutation in the COL6A2 gene had not previously been reported, yielding implications for genetic counseling. </p><p>In a 61-year-old man, born of consanguineous parents, with autosomal recessive Bethlem myopathy-1B, Zamurs et al. (2015) identified a homozygous missense mutation in the COL6A2 gene (D871N; 120240.0019). His unaffected parents were each heterozygous for the variant. Detailed studies of patient fibroblasts showed that the mutant protein interfered with collagen VI assembly, secretion, and microfibril formation, all of which were reduced compared to controls. Some collagen VI was assembled, albeit more slowly than normal, and was secreted; these molecules contained the minor COL6A2 C2a splice form that has an alternative C terminus and does not contain the mutation. When expressed in HEK293 cells, the mutant D871N protein was retained in the endoplasmic reticulum due to abnormal protein folding and was selectively degraded by the proteosome. </p><p>In 2 adult sibs with autosomal recessive Bethlem myopathy-1B, Caria et al. (2019) identified compound heterozygous mutations in the COL6A2 gene: a nonsense mutation in exon 28, resulting in a gln889-to-ter (Q889X; 120240.0022) and an in-frame insertion (120240.0023) in exon 5. The mutations, which were found by next-generation panel sequencing and confirmed by Sanger sequencing, were each inherited from an unaffected parent. Western blot analysis of patient fibroblasts showed low levels of the canonical 1,019-residue COL6A2 chain and presence of a truncated 889-residue mutant protein; a normal 918-residue splice variant (C2a) was also detected. There were normal amounts of collagen VI dimers and tetramers in the cell layer, but not in the cell media, indicating instability of the secreted protein. Immunofluorescence studies of patient fibroblasts showed markedly reduced expression of collagen VI that was poorly organized in the extracellular matrix. </p>
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<strong>REFERENCES</strong>
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Lucioli, S., Giusti, B., Mercuri, E., Vanegas, O. C., Lucarini, L., Pietroni, V., Urtizberea, A., Ben Yaou, R., de Visser, M., van der Kooi, A. J., Bonnemann, C., Iannaccone, S. T., Merlini, L., Bushby, K., Muntoni, F., Bertini, E., Chu, M.-L., Pepe, G.
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