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- #158810 - BETHLEM MYOPATHY 1A; BTHLM1A
- OMIM
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<span class="h4">#158810</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/158810"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS603511,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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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#seeAlso"><strong>See Also</strong></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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<a href="#creationDate"><strong>Creation Date</strong></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 style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=367&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Bethlem muscular dystrophy&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=31799&Typ=Pat" title="Collagen VI-related congenital muscular dystrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Collagen VI-related congen…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=31800&Typ=Pat" title="Intermediate collagen VI-related muscular dystrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Intermediate collagen VI-r…&nbsp;</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>
<div><a href="https://www.diseaseinfosearch.org/x/818" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=158810[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Bethlem muscular dystrophy</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=646098" title="Collagen VI-related congenital muscular dystrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Collagen VI-related congen…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=646113" title="Intermediate collagen VI-related muscular dystrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Intermediate collagen VI-r…</a></div>
</div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0050663" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/158810" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA002260/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0050663" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:158810" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<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.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 718572004<br />
<strong>ORPHA:</strong> 610, 646098, 646113<br />
<strong>DO:</strong> 0050663<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
158810
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
BETHLEM MYOPATHY 1A; BTHLM1A
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
BETHLEM MYOPATHY 1; BTHLM1<br />
BETHLEM MYOPATHY<br />
MYOPATHY, BENIGN CONGENITAL, WITH CONTRACTURES<br />
MUSCULAR DYSTROPHY, BENIGN CONGENITAL
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/21/174?start=-3&limit=10&highlight=174">
21q22.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Bethlem myopathy 1A
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/158810"> 158810 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
COL6A1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120220"> 120220 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/158810" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS603511,PS158810" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/158810" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/158810" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Torticollis, congenital (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/268240006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">268240006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q68.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q68.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0079352&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0079352</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005988" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005988</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005988" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005988</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- No cardiac involvement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839628&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839628</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Respiratory failure due to muscle weakness may occur in late stages <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805752&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805752</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409622000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409622000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J96.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J96.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</a>]</span><br />
</span>
</div>
</div>
</div>
<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> 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 /> -
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 /> -
Joint hyperlaxity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001388</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">
- Joint hyperlaxity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001388</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">
- Delayed motor milestones <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854301</a> 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> <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 /> -
Muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26544005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26544005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151786</a>, <a href="https://bioportal.bioontology.org/search?q=C0030552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030552</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span><br /> -
Proximal muscle weakness (more severe than distal muscle weakness) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936213&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936213</a>]</span> <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">[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 /> -
Extensor muscle weakness (more severe than flexor muscle weakness) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936214</a>]</span><br /> -
Muscle weakness, limb-girdle <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858127&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858127</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003325</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003325</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 /> -
Difficulty walking and climbing stairs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1970213&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1970213</a>]</span><br /> -
Muscle atrophy, mild, more proximal than distal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834678&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834678</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br /> -
Hypotonia, in neonatal onset <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205294008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205294008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2267233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2267233</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span><br /> -
Myopathic changes, nonspecific, seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4228976&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4228976</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/129565002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">129565002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G72.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G72.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M60-M63" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M60-M63</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/359.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">359.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003198" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003198</a>]</span><br /> -
Dystrophic changes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276192&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276192</a>]</span><br /> -
Internal nuclei <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836163&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836163</a>]</span><br /> -
Fiber size variability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552710&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552710</a>]</span><br /> -
Endomysial fibrosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4022161&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4022161</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100297</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100297</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Movement </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Decreased fetal movements (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276369006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276369006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.8190" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.8190</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235659&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235659</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Normal or increased serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837349&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837349</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset usually in early childhood, although ranges from birth to adulthood<br /> -
Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
Slow progression <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 /> -
Approximately half of patients need ambulatory support after the fifth decade<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the collagen VI, alpha-1 polypeptide gene (COL6A1, <a href="/entry/120220#0001">120220.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Bethlem myopathy
- <a href="/phenotypicSeries/PS158810">PS158810</a>
- 4 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/1149?start=-3&limit=10&highlight=1149"> 2q37.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620726"> Bethlem myopathy 1C </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620726"> 620726 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120250"> COL6A3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120250"> 120250 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/650?start=-3&limit=10&highlight=650"> 6q13-q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616471"> Bethlem myopathy 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616471"> 616471 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120320"> COL12A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120320"> 120320 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/21/174?start=-3&limit=10&highlight=174"> 21q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/158810"> Bethlem myopathy 1A </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/158810"> 158810 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120220"> COL6A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120220"> 120220 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/21/175?start=-3&limit=10&highlight=175"> 21q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620725"> Bethlem myopathy 1B </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620725"> 620725 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120240"> COL6A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120240"> 120240 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Muscular dystrophy, limb-girdle, autosomal dominant
- <a href="/phenotypicSeries/PS603511">PS603511</a>
- 6 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
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<strong>Inheritance</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
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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">
<strong>Gene/Locus</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
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</thead>
<tbody>
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<td>
<span class="mim-font">
<a href="/geneMap/3/73?start=-3&limit=10&highlight=73"> 3p25.1-p23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613530"> Muscular dystrophy, limb-girdle, type 1H </a>
</span>
</td>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
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<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613530"> 613530 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613530"> LGMD1H </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613530"> 613530 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/363?start=-3&limit=10&highlight=363"> 4q21.22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609115"> Muscular dystrophy, limb-girdle, autosomal dominant 3 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609115"> 609115 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607137"> HNRNPDL </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607137"> 607137 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/663?start=-3&limit=10&highlight=663"> 7q32.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608423"> Muscular dystrophy, limb-girdle, autosomal dominant 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608423"> 608423 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610032"> TNPO3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610032"> 610032 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/862?start=-3&limit=10&highlight=862"> 7q36.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603511"> Muscular dystrophy, limb-girdle, autosomal dominant 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603511"> 603511 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611332"> DNAJB6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611332"> 611332 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/133?start=-3&limit=10&highlight=133"> 15q15.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618129"> Muscular dystrophy, limb-girdle, autosomal dominant 4 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618129"> 618129 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/114240"> CAPN3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/114240"> 114240 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/21/174?start=-3&limit=10&highlight=174"> 21q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/158810"> Bethlem myopathy 1A </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/158810"> 158810 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120220"> COL6A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120220"> 120220 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Bethlem myopathy-1A (BTHLM1A) is caused by heterozygous mutation in the COL6A1 gene (<a href="/entry/120220">120220</a>) on chromosome 21q22.</p><p>See also Ullrich congenital muscular dystrophy-1A (UCMD1A; <a href="/entry/254090">254090</a>), an allelic disorder with a more severe phenotype.</p>
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<strong>Description</strong>
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<p>Bethlem myopathy-1 (BTHLM1) is a congenital muscular dystrophy characterized by distal joint laxity and a combination of distal and proximal joint contractures. The age at onset is highly variable, ranging from infancy to adulthood. Disease 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. &lt;strong&gt;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.&lt;/strong&gt; Hum. Mutat. 34: 1558-1567, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24038877/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24038877&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24038877[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22429&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24038877">Butterfield et al., 2013</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'})"><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>Genetic Heterogeneity of Bethlem Myopathy</em></strong></p><p>
See Bethlem myopathy-1B (BTHLM1B; <a href="/entry/620725">620725</a>), caused by mutation in the COL6A2 gene (<a href="/entry/120240">120240</a>) on chromosome 21q22; Bethlem myopathy-1C (<a href="/entry/620726">620726</a>), caused by mutation the COL6A3 gene (<a href="/entry/120250">120250</a>) on chromosome 2q37; and Bethlem myopathy-2 (BTHLM2; <a href="/entry/616471">616471</a>), caused by mutation in the COL12A1 gene (<a href="/entry/120320">120320</a>) on chromosome 6q13-q14.</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="#21" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. &lt;strong&gt;229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.&lt;/strong&gt; Neuromusc. Disord. 28: 702-710, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30055862/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30055862&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2018.05.007&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" 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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<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
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<strong>Clinical Features</strong>
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<p><a href="#1" class="mim-tip-reference" title="Bethlem, J., van Wijngaarden, G. K. &lt;strong&gt;Benign myopathy, with autosomal dominant inheritance--a report on three pedigrees.&lt;/strong&gt; Brain 99: 91-100, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/963533/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;963533&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/99.1.91&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="963533">Bethlem and van Wijngaarden (1976)</a> described 3 Dutch families in which 28 patients suffered from benign myopathy with autosomal dominant inheritance. The onset was in early infancy, progression was slow, and many patients reached an advanced age. The patients had moderate weakness and atrophy of the muscles of the trunk and limbs, the proximal muscles being more involved than the distal muscles, and the extensors more than the flexors. Early flexion contractures of the elbow and interphalangeal joints of the last 4 fingers, and plantar flexion contractures of the ankles were constant findings. In contrast to Emery-Dreifuss muscular dystrophy (<a href="/entry/310300">310300</a>), contractures of the neck and spine were rarely seen (<a href="#17" class="mim-tip-reference" title="Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G. &lt;strong&gt;Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).&lt;/strong&gt; Neurology 38: 573-580, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3352914/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3352914&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.38.4.573&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3352914">Mohire et al., 1988</a>). Moreover, 4 of the 28 patients had congenital torticollis. The serum creatine phosphokinase activity was usually not elevated, and histopathologic findings were nonspecific. Genealogic investigations showed no relationship between these 3 families which had lived in the Netherlands from at least the beginning of the 18th century. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=963533+3352914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Schmalbruch, H., Kamieniecka, Z., Fuglsang-Frederiksen, A., Trojaborg, W. &lt;strong&gt;Benign congenital muscular dystrophy with autosomal dominant heredity: problems of classification.&lt;/strong&gt; J. Neurol. 234: 146-151, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3585421/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3585421&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00314133&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3585421">Schmalbruch et al. (1987)</a> described a family in which members of both sexes in 3 generations had a benign form of congenital muscular dystrophy. Onset of symptoms was in early childhood and progression, if any, was slow. The proximal limb muscles, the sternocleidomastoid, and anterior tibial muscles were affected. One patient had torticollis and all had heel-cord shortening. There was no cardiomyopathy. Creatine kinase was elevated, and a histologic study showed necrotizing myopathy with pronounced regeneration and formation of aberrant myofibrils (ringbinden) and fibrosis. <a href="#12" class="mim-tip-reference" title="Leyten, Q. H., Gabreels, F. J. M., Joosten, E. M. G., Renier, W. O., Ter Laak, H. J., Ter Haar, B. G. A., Stadhouders, A. M. &lt;strong&gt;An autosomal dominant type of congenital muscular dystrophy.&lt;/strong&gt; Brain Dev. 8: 533-537, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3799922/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3799922&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0387-7604(86)80099-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3799922">Leyten et al. (1986)</a> described father and daughter with congenital muscular dystrophy. Mitochondrial abnormalities were found on muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3585421+3799922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Merlini, L., Morandi, L., Granata, C., Ballestrazzi, A. &lt;strong&gt;Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures: description of two new families.&lt;/strong&gt; Neuromusc. Disord. 4: 503-511, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7881296/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7881296&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0960-8966(94)90091-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7881296">Merlini et al. (1994)</a> described 2 families with early-onset, benign, autosomal dominant myopathy with contractures and reviewed 6 previously reported families with Bethlem myopathy. In both families, there were several instances of male-to-male transmission. Fifteen of the 21 examined members proved to have myopathy with contractures, although several of them were so mildly affected that they considered themselves asymptomatic. Electromyography demonstrated a myopathic pattern, and nerve conduction tests were normal. CT scan demonstrated unexpectedly severe fatty replacement of paravertebral muscles and relatively preserved gluteal muscles. <a href="#16" class="mim-tip-reference" title="Merlini, L., Morandi, L., Granata, C., Ballestrazzi, A. &lt;strong&gt;Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures: description of two new families.&lt;/strong&gt; Neuromusc. Disord. 4: 503-511, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7881296/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7881296&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0960-8966(94)90091-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7881296">Merlini et al. (1994)</a> suggested that the hallmark of Bethlem myopathy was contractures of the last 4 fingers. Elbow contractures were also present in more than half the subjects, but the severity was not as great as that seen in Emery muscular dystrophy. There was no cardiac or respiratory involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7881296" 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="#22" class="mim-tip-reference" title="Tohyama, J., Inagaki, M., Nonaka, I. &lt;strong&gt;Early onset muscular dystrophy with autosomal dominant heredity: report of a family and CT findings of skeletal muscle.&lt;/strong&gt; Brain Dev. 16: 402-406, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7892962/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7892962&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0387-7604(94)90130-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7892962">Tohyama et al. (1994)</a> described an affected mother and daughter with contractures and mild proximal weakness. Muscle biopsy showed dystrophic features with evidence of fiber necrosis and regeneration. CT scanning demonstrated decreased volume of paravertebral muscles and low densities in various proximal muscles with essentially normal distal musculature. <a href="#22" class="mim-tip-reference" title="Tohyama, J., Inagaki, M., Nonaka, I. &lt;strong&gt;Early onset muscular dystrophy with autosomal dominant heredity: report of a family and CT findings of skeletal muscle.&lt;/strong&gt; Brain Dev. 16: 402-406, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7892962/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7892962&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0387-7604(94)90130-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7892962">Tohyama et al. (1994)</a> distinguished their cases from Bethlem myopathy because of dystrophic changes seen in muscle biopsy. However, the clinical presentation of both the Bethlem cases and these reported were similar. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7892962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Speer, M. C., Yamaoka, L. H., Stajich, J., Lewis, K., Pericak-Vance, M. A., Stacy, R., Tandan, R., Fries, T. J. &lt;strong&gt;Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 58: 197-198, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8533815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8533815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320580220&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8533815">Speer et al. (1995)</a> noted that Bethlem myopathy shows a distribution of proximal muscle weakness similar to that observed in autosomal dominant limb-girdle muscular dystrophy (see, e.g., LGMDD1, <a href="/entry/603511">603511</a>). They stated that it differs from most LGMDs in 2 ways: first, Bethlem myopathy presents with joint contractures, most commonly observed at the elbows, ankles, and neck; second, onset in Bethlem myopathy is in early childhood, whereas most dominant LGMDs show adult onset (<a href="#20" class="mim-tip-reference" title="Speer, M. C., Yamaoka, L. H., Stajich, J., Lewis, K., Pericak-Vance, M. A., Stacy, R., Tandan, R., Fries, T. J. &lt;strong&gt;Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 58: 197-198, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8533815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8533815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320580220&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8533815">Speer et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Jobsis, G. J., Boers, J. M., Barth, P. G., de Visser, M. &lt;strong&gt;Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures.&lt;/strong&gt; Brain 122: 649-655, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10219778/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10219778&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/122.4.649&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10219778">Jobsis et al. (1999)</a> noted that Bethlem myopathy is a progressive disorder in adulthood, with many patients needing a wheelchair after age 50. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219778" 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="Haq, R. U., Speer, M. C., Chu, M.-L., Tandan, R. &lt;strong&gt;Respiratory muscle involvement in Bethlem myopathy.&lt;/strong&gt; Neurology 52: 174-176, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9921869/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9921869&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.52.1.174&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9921869">Haq et al. (1999)</a> reported progressive respiratory failure caused by diaphragmatic paralysis in a patient with Bethlem myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921869" 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="Lampe, A. K., Bushby, K. M. D. &lt;strong&gt;Collagen VI related muscle disorders.&lt;/strong&gt; J. Med. Genet. 42: 673-685, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16141002/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16141002&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2002.002311&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16141002">Lampe and Bushby (2005)</a> provided a review of collagen VI-related muscle disorders. The development of contractures is a hallmark of Bethlem myopathy. The contractures may appear and disappear in various joints during childhood, but nearly all patients eventually show flexion contractures of the fingers, wrists, elbows, and ankles, and these, in addition to weakness, contribute to disability. <a href="#10" class="mim-tip-reference" title="Lampe, A. K., Bushby, K. M. D. &lt;strong&gt;Collagen VI related muscle disorders.&lt;/strong&gt; J. Med. Genet. 42: 673-685, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16141002/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16141002&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2002.002311&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16141002">Lampe and Bushby (2005)</a> pictured unusual skin features that may be present in some Bethlem myopathy patients, including follicular hyperkeratosis, keloid formation, and 'cigarette paper' scarring over the knees. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16141002" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="inheritance" class="mim-anchor"></a>
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<p>Bethlem myopathy-1A is inherited in an autosomal dominant pattern (<a href="#8" 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. &lt;strong&gt;Genetic localization of Bethlem myopathy.&lt;/strong&gt; Neurology 46: 779-782, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8618682/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8618682&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.46.3.779&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8618682">Jobsis et al., 1996</a>). <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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<p>In 6 Dutch families with Bethlem myopathy, <a href="#8" 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. &lt;strong&gt;Genetic localization of Bethlem myopathy.&lt;/strong&gt; Neurology 46: 779-782, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8618682/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8618682&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.46.3.779&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" 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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<p><a href="#6" class="mim-tip-reference" title="Hicks, D., Lampe, A. K., Barresi, R., Charleton, R., Fiorillo, C., Bonnemann, C. G., Hudson, J., Sutton, R., Lochmuller, H., Straub, V., Bushby, K. &lt;strong&gt;A refined diagnostic algorithm for Bethlem myopathy.&lt;/strong&gt; Neurology 70: 1192-1199, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18378883/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18378883&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000307749.66438.6d&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18378883">Hicks et al. (2008)</a> found that immunofluorescence labeling of collagen VI in skin biopsy-derived fibroblast cultures from patients suspected of having Bethlem myopathy was highly predictive of a COL6A mutation compared to immunofluorescence for collagen VI and basal lamina-located perlecan (HSPG2; <a href="/entry/142461">142461</a>) in muscle samples. Abnormalities in the fibroblast labeling pattern of collagen VI were detected in more than 78% of genetically confirmed patients. Among 19 patients with an unknown genotype, the fibroblast technique providing a 75% positive predictive value, 100% sensitivity and negative predictive values, and specificity of 63%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18378883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#15" class="mim-tip-reference" title="Merlini, L., Angelin, A., Tiepolo, T., Braghetta, P., Sabatelli, P., Zamparelli, A., Ferlini, A., Maraldi, N. M., Bonaldo, P., Bernardi, P. &lt;strong&gt;Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies.&lt;/strong&gt; Proc. Nat. Acad. Sci. 105: 5225-5229, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18362356/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18362356&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18362356[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0800962105&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18362356">Merlini et al. (2008)</a> found that treatment of a patient with Bethlem myopathy and 4 UCMD patients with 2 divided doses of orally administered cyclosporin A resulted in decreased mitochondrial dysfunction and apoptosis in skeletal muscle biopsies 1 month later. Cellular signs of muscle regeneration were also observed. Clinical response could not be assessed because of the limited time frame, but the study provided a proof of principle and indicated that mitochondrial dysfunction plays a critical role in the pathogenesis of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18362356" 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 affected members of a kindred (family 2, originally reported by <a href="#1" class="mim-tip-reference" title="Bethlem, J., van Wijngaarden, G. K. &lt;strong&gt;Benign myopathy, with autosomal dominant inheritance--a report on three pedigrees.&lt;/strong&gt; Brain 99: 91-100, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/963533/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;963533&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/99.1.91&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="963533">Bethlem and van Wijngaarden, 1976</a>) with Bethlem myopathy, <a href="#9" 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. &lt;strong&gt;Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures.&lt;/strong&gt; Nature Genet. 14: 113-115, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8782832/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8782832&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0996-113&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8782832">Jobsis et al. (1996)</a> demonstrated a heterozygous missense mutation in the COL6A1 gene (G286V; <a href="/entry/120220#0001">120220.0001</a>). In affected members from 2 other kindreds, <a href="#9" 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. &lt;strong&gt;Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures.&lt;/strong&gt; Nature Genet. 14: 113-115, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8782832/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8782832&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0996-113&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" 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>); see BTHLM1B (<a href="/entry/620725">620725</a>). 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, these observations suggested to <a href="#9" 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. &lt;strong&gt;Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures.&lt;/strong&gt; Nature Genet. 14: 113-115, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8782832/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8782832&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0996-113&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8782832">Jobsis et al. (1996)</a> a similar mechanism in Bethlem myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=963533+8782832" 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 an Italian family with Bethlem myopathy previously reported by <a href="#16" class="mim-tip-reference" title="Merlini, L., Morandi, L., Granata, C., Ballestrazzi, A. &lt;strong&gt;Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures: description of two new families.&lt;/strong&gt; Neuromusc. Disord. 4: 503-511, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7881296/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7881296&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0960-8966(94)90091-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7881296">Merlini et al. (1994)</a>, <a href="#23" class="mim-tip-reference" title="Vanegas, O. C., Zhang, R.-Z., Sabatelli, P., Lattanzi, G., Bencivenga, P., Giusti, B., Columbaro, M., Chu, M.-L., Merlini, L., Pepe, G. &lt;strong&gt;Novel COL6A1 splicing mutation in a family affected by mild Bethlem myopathy.&lt;/strong&gt; Muscle Nerve 25: 513-519, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11932968/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11932968&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mus.10100&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11932968">Vanegas et al. (2002)</a> identified a heterozygous splice site mutation in the COL6A1 gene (<a href="/entry/120220#0008">120220.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7881296+11932968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B. &lt;strong&gt;Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.&lt;/strong&gt; J. Med. Genet. 42: 108-120, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15689448/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15689448&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2004.023754&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15689448">Lampe et al. (2005)</a> sequenced all 3 COL6 genes from genomic DNA in 79 patients with Ullrich congenital muscular dystrophy (UCMD; <a href="/entry/254090">254090</a>) or Bethlem myopathy, and found putative mutations in 1 of the COL6 genes in 62% of patients. Some patients showed changes in more than one of the COL6 genes, and some UCMD patients appeared to have dominant rather than recessive disease. <a href="#11" class="mim-tip-reference" title="Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B. &lt;strong&gt;Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.&lt;/strong&gt; J. Med. Genet. 42: 108-120, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15689448/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15689448&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2004.023754&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15689448">Lampe et al. (2005)</a> concluded that these findings may explain some or all of the cases of UCMD that are unlinked to the COL6 gene under a recessive model and noted that the large number of SNPs generated in this study may be of importance in determining the major phenotypic variability seen in this group of disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="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. &lt;strong&gt;Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy.&lt;/strong&gt; Neurology 64: 1931-1937, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15955946/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15955946&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.WNL.0000163990.00057.66&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15955946">Lucioli et al. (2005)</a> identified 8 different mutations in the COL6A1 gene in 16 of 30 unrelated probands with a clinical diagnosis of Bethlem myopathy; 2 of the 30 probands had a mutation in the COL6A2 gene and the COL6A3 gene, respectively. The most common COL6A1 mutation was a splice site mutation (<a href="/entry/120220#0006">120220.0006</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'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Brinas, L., Richard, P., Quijano-Roy, S., Gartioux, C., Ledeuil, C., Lacene, E., Makri, S., Ferreiro, A., Maugenre, S., Topaloglu, H., Haliloglu, G., Penisson-Besnier, I., and 26 others. &lt;strong&gt;Early onset collagen VI myopathies: genetic and clinical correlations.&lt;/strong&gt; Ann. Neurol. 68: 511-520, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20976770/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20976770&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.22087&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20976770">Brinas et al. (2010)</a> classified 49 patients with muscular dystrophy due to mutations in 1 of the 3 COL6A genes into 3 clinical groups: 9 (18%) had a severe phenotype with contractures and never achieved ambulation, 26 (53%) had a moderate phenotype and were initially able to walk but tended to lose ambulation later in childhood, and 14 (29%) had a milder course and remained ambulatory at a mean age of 20 years. All patient fibroblasts showed absent or reduced COL6A secretion, with frequent intracellular retention, and the decreased levels correlated with increased disease severity. Genetic analysis showed equal distribution of mutations across the cohort: 17 (30%) in COL6A1, 26 (46%) in COL6A2, and 13 (23%) in COL6A3. Thirty patients (61%) had dominant de novo mutations, and 18 had recessive mutations. Fourteen patients (28.5%) had truncating mutations. Homozygous truncating mutations before or within the triple helix (TH) domain were associated with the most severe phenotypes. The moderate phenotype was associated with heterozygous mutations resulting in the skipping of part of the TH domains or affecting the glycine residue of the Gly-X-Y domain. RT-PCR analysis was helpful in defining the effect of splice site mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20976770" 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>Substitutions in the conserved Gly-X-Y motif in the triple helix (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies, accounting for almost one-third of all pathogenic mutations. <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. &lt;strong&gt;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.&lt;/strong&gt; Hum. Mutat. 34: 1558-1567, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24038877/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24038877&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24038877[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22429&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24038877">Butterfield et al. (2013)</a> analyzed genotype/phenotype correlations of 194 individuals with glycine substitutions in the TH domain of the COL6A1, COL6A2, or COL6A3 genes. The cohort included 97 newly reported cases and 97 published cases. In all 3 genes, 89% of the mutations clustered in the N-terminal regions before the 17th Gly-X-Y triplet (TH17). This important landmark is delineated by cysteine residues in the COL6A3 chain, which form disulfide bonds stabilizing tetramers. Patients with mutations inside the critical region of Gly-X-Y triplets 10-15 tended to have a more severe phenotype than those with mutations outside this critical region. However, identical glycine substitutions were associated with both severe and mild phenotypes. The most commonly observed mutation was G284R in the COL6A1 gene (<a href="/entry/120220#0012">120220.0012</a>), found in 28 cases with variable phenotypes. Glycine substitutions in the TH domain were dominantly acting in 96% of cases, and recessive mutations tended to occur in the C-terminal end of the TH domain. <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. &lt;strong&gt;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.&lt;/strong&gt; Hum. Mutat. 34: 1558-1567, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24038877/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24038877&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24038877[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22429&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24038877">Butterfield et al. (2013)</a> concluded that the clustering of glycine substitutions in this region is not based on features of the primary sequence, but rather reflects a functional importance of this domain. <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'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#14" class="mim-tip-reference" title="Menazza, S., Blaauw, B., Tiepolo, T., Toniolo, L., Braghetta, P., Spolaore, B., Reggiani, C., Di Lisa, F., Bonaldo, P., Canton, M. &lt;strong&gt;Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 19: 4207-4215, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20716577/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20716577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddq339&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20716577">Menazza et al. (2010)</a> investigated whether reactive oxygen species (ROS) produced in mitochondria by monoamine oxidase (MAO) contribute to muscular dystrophy pathogenesis. Pargyline, an MAO inhibitor, reduced ROS accumulation along with a beneficial effect on the dystrophic phenotype of Col6a1 -/- mice, a model of Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD; <a href="/entry/254090">254090</a>), and mdx mice, a model of Duchenne muscular dystrophy (<a href="/entry/310200">310200</a>). Oxidation of myofibrillar proteins, as probed by formation of disulfide crossbridges in tropomyosin (see <a href="/entry/191010">191010</a>), was detected in both Col6a1 -/- and mdx muscles. Notably, pargyline significantly reduced myofiber apoptosis and ameliorated muscle strength in Col6a1 -/- mice. <a href="#14" class="mim-tip-reference" title="Menazza, S., Blaauw, B., Tiepolo, T., Toniolo, L., Braghetta, P., Spolaore, B., Reggiani, C., Di Lisa, F., Bonaldo, P., Canton, M. &lt;strong&gt;Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy.&lt;/strong&gt; Hum. Molec. Genet. 19: 4207-4215, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20716577/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20716577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddq339&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20716577">Menazza et al. (2010)</a> concluded that there is a novel and determinant role of MAO in muscular dystrophies, adding evidence of the pivotal role of mitochondria and suggesting a therapeutic potential for MAO inhibition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20716577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>See Also:</strong>
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<a href="#Gualandi2009" 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. &lt;strong&gt;Autosomal recessive Bethlem myopathy.&lt;/strong&gt; Neurology 73: 1883-1891, 2009.">Gualandi et al. (2009)</a>; <a href="#Speer1996" class="mim-tip-reference" title="Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A. &lt;strong&gt;Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.&lt;/strong&gt; Hum. Molec. Genet. 5: 1043-1046, 1996.">Speer et al. (1996)</a>
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<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<a id="1" class="mim-anchor"></a>
<a id="Bethlem1976" class="mim-anchor"></a>
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<p class="mim-text-font">
Bethlem, J., van Wijngaarden, G. K.
<strong>Benign myopathy, with autosomal dominant inheritance--a report on three pedigrees.</strong>
Brain 99: 91-100, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/963533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">963533</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=963533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/99.1.91" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
<a id="Brinas2010" class="mim-anchor"></a>
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Brinas, L., Richard, P., Quijano-Roy, S., Gartioux, C., Ledeuil, C., Lacene, E., Makri, S., Ferreiro, A., Maugenre, S., Topaloglu, H., Haliloglu, G., Penisson-Besnier, I., and 26 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20976770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20976770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20976770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ana.22087" target="_blank">Full Text</a>]
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<a id="Butterfield2013" class="mim-anchor"></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.
<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://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>]
[<a href="https://doi.org/10.1002/humu.22429" target="_blank">Full Text</a>]
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<a id="Gualandi2009" class="mim-anchor"></a>
<div class="">
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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.
<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://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>]
[<a href="https://doi.org/10.1212/WNL.0b013e3181c3fd2a" target="_blank">Full Text</a>]
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<a id="Haq1999" class="mim-anchor"></a>
<div class="">
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Haq, R. U., Speer, M. C., Chu, M.-L., Tandan, R.
<strong>Respiratory muscle involvement in Bethlem myopathy.</strong>
Neurology 52: 174-176, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921869</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/wnl.52.1.174" target="_blank">Full Text</a>]
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<a id="Hicks2008" class="mim-anchor"></a>
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Hicks, D., Lampe, A. K., Barresi, R., Charleton, R., Fiorillo, C., Bonnemann, C. G., Hudson, J., Sutton, R., Lochmuller, H., Straub, V., Bushby, K.
<strong>A refined diagnostic algorithm for Bethlem myopathy.</strong>
Neurology 70: 1192-1199, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18378883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18378883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18378883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000307749.66438.6d" target="_blank">Full Text</a>]
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<a id="Jobsis1999" class="mim-anchor"></a>
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Jobsis, G. J., Boers, J. M., Barth, P. G., de Visser, M.
<strong>Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures.</strong>
Brain 122: 649-655, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219778</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219778" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/122.4.649" target="_blank">Full Text</a>]
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<a id="Jobsis1996" class="mim-anchor"></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.
<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://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'})">related citations</a>]
[<a href="https://doi.org/10.1212/wnl.46.3.779" target="_blank">Full Text</a>]
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<a id="Jobsis1996" class="mim-anchor"></a>
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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.
<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://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>]
[<a href="https://doi.org/10.1038/ng0996-113" target="_blank">Full Text</a>]
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<a id="Lampe2005" class="mim-anchor"></a>
<div class="">
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Lampe, A. K., Bushby, K. M. D.
<strong>Collagen VI related muscle disorders.</strong>
J. Med. Genet. 42: 673-685, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16141002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16141002</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16141002" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2002.002311" target="_blank">Full Text</a>]
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<a id="Lampe2005" class="mim-anchor"></a>
<div class="">
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Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B.
<strong>Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.</strong>
J. Med. Genet. 42: 108-120, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689448</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2004.023754" target="_blank">Full Text</a>]
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<a id="Leyten1986" class="mim-anchor"></a>
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Leyten, Q. H., Gabreels, F. J. M., Joosten, E. M. G., Renier, W. O., Ter Laak, H. J., Ter Haar, B. G. A., Stadhouders, A. M.
<strong>An autosomal dominant type of congenital muscular dystrophy.</strong>
Brain Dev. 8: 533-537, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3799922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3799922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3799922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0387-7604(86)80099-7" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
<a id="Lucioli2005" class="mim-anchor"></a>
<div class="">
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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.
<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://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>]
[<a href="https://doi.org/10.1212/01.WNL.0000163990.00057.66" target="_blank">Full Text</a>]
</p>
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<a id="14" class="mim-anchor"></a>
<a id="Menazza2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Menazza, S., Blaauw, B., Tiepolo, T., Toniolo, L., Braghetta, P., Spolaore, B., Reggiani, C., Di Lisa, F., Bonaldo, P., Canton, M.
<strong>Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy.</strong>
Hum. Molec. Genet. 19: 4207-4215, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20716577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20716577</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20716577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddq339" target="_blank">Full Text</a>]
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<a id="Merlini2008" class="mim-anchor"></a>
<div class="">
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Merlini, L., Angelin, A., Tiepolo, T., Braghetta, P., Sabatelli, P., Zamparelli, A., Ferlini, A., Maraldi, N. M., Bonaldo, P., Bernardi, P.
<strong>Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies.</strong>
Proc. Nat. Acad. Sci. 105: 5225-5229, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18362356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18362356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18362356[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=18362356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.0800962105" target="_blank">Full Text</a>]
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<a id="Merlini1994" class="mim-anchor"></a>
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Merlini, L., Morandi, L., Granata, C., Ballestrazzi, A.
<strong>Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures: description of two new families.</strong>
Neuromusc. Disord. 4: 503-511, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7881296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7881296</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7881296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0960-8966(94)90091-4" target="_blank">Full Text</a>]
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<a id="Mohire1988" class="mim-anchor"></a>
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Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G.
<strong>Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).</strong>
Neurology 38: 573-580, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3352914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3352914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3352914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/wnl.38.4.573" target="_blank">Full Text</a>]
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<a id="Schmalbruch1987" class="mim-anchor"></a>
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Schmalbruch, H., Kamieniecka, Z., Fuglsang-Frederiksen, A., Trojaborg, W.
<strong>Benign congenital muscular dystrophy with autosomal dominant heredity: problems of classification.</strong>
J. Neurol. 234: 146-151, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3585421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3585421</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3585421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00314133" target="_blank">Full Text</a>]
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<a id="Speer1996" class="mim-anchor"></a>
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Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A.
<strong>Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.</strong>
Hum. Molec. Genet. 5: 1043-1046, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/5.7.1043" target="_blank">Full Text</a>]
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<a id="Speer1995" class="mim-anchor"></a>
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Speer, M. C., Yamaoka, L. H., Stajich, J., Lewis, K., Pericak-Vance, M. A., Stacy, R., Tandan, R., Fries, T. J.
<strong>Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A. (Letter)</strong>
Am. J. Med. Genet. 58: 197-198, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320580220" 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.
<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://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>]
[<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank">Full Text</a>]
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<a id="Tohyama1994" class="mim-anchor"></a>
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Tohyama, J., Inagaki, M., Nonaka, I.
<strong>Early onset muscular dystrophy with autosomal dominant heredity: report of a family and CT findings of skeletal muscle.</strong>
Brain Dev. 16: 402-406, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7892962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0387-7604(94)90130-9" target="_blank">Full Text</a>]
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<a id="Vanegas2002" class="mim-anchor"></a>
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Vanegas, O. C., Zhang, R.-Z., Sabatelli, P., Lattanzi, G., Bencivenga, P., Giusti, B., Columbaro, M., Chu, M.-L., Merlini, L., Pepe, G.
<strong>Novel COL6A1 splicing mutation in a family affected by mild Bethlem myopathy.</strong>
Muscle Nerve 25: 513-519, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11932968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11932968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11932968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/mus.10100" target="_blank">Full Text</a>]
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George E. Tiller - updated : 06/22/2017
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Cassandra L. Kniffin - updated : 12/3/2013<br>Cassandra L. Kniffin - updated : 10/17/2011<br>Cassandra L. Kniffin - updated : 1/28/2011<br>Cassandra L. Kniffin - updated : 10/17/2008<br>Cassandra L. Kniffin - updated : 7/2/2008<br>Cassandra L. Kniffin - updated : 5/16/2008<br>Victor A. McKusick - updated : 12/20/2005<br>Cassandra L. Kniffin - updated : 11/1/2005<br>Moyra Smith - updated : 8/15/1996<br>Orest Hurko - updated : 5/8/1996<br>Orest Hurko - updated : 9/8/1995
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Creation Date:
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Victor A. McKusick : 7/2/1987
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carol : 07/17/2024
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<strong>#</strong> 158810
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BETHLEM MYOPATHY 1A; BTHLM1A
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<em>Alternative titles; symbols</em>
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BETHLEM MYOPATHY 1; BTHLM1<br />
BETHLEM MYOPATHY<br />
MYOPATHY, BENIGN CONGENITAL, WITH CONTRACTURES<br />
MUSCULAR DYSTROPHY, BENIGN CONGENITAL
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<strong>SNOMEDCT:</strong> 718572004; &nbsp;
<strong>ORPHA:</strong> 610, 646098, 646113; &nbsp;
<strong>DO:</strong> 0050663; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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21q22.3
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Bethlem myopathy 1A
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158810
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Autosomal dominant
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3
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COL6A1
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120220
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Bethlem myopathy-1A (BTHLM1A) is caused by heterozygous mutation in the COL6A1 gene (120220) on chromosome 21q22.</p><p>See also Ullrich congenital muscular dystrophy-1A (UCMD1A; 254090), an allelic disorder with a more severe phenotype.</p>
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<strong>Description</strong>
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<p>Bethlem myopathy-1 (BTHLM1) is a congenital muscular dystrophy characterized by distal joint laxity and a combination of distal and proximal joint contractures. The age at onset is highly variable, ranging from infancy to adulthood. Disease progression is slow and ambulation is usually retained into adulthood (summary by Butterfield et al., 2013). </p><p><strong><em>Genetic Heterogeneity of Bethlem Myopathy</em></strong></p><p>
See Bethlem myopathy-1B (BTHLM1B; 620725), caused by mutation in the COL6A2 gene (120240) on chromosome 21q22; Bethlem myopathy-1C (620726), caused by mutation the COL6A3 gene (120250) on chromosome 2q37; and Bethlem myopathy-2 (BTHLM2; 616471), caused by mutation in the COL12A1 gene (120320) on chromosome 6q13-q14.</p>
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<strong>Nomenclature</strong>
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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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<strong>Clinical Features</strong>
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<p>Bethlem and van Wijngaarden (1976) described 3 Dutch families in which 28 patients suffered from benign myopathy with autosomal dominant inheritance. The onset was in early infancy, progression was slow, and many patients reached an advanced age. The patients had moderate weakness and atrophy of the muscles of the trunk and limbs, the proximal muscles being more involved than the distal muscles, and the extensors more than the flexors. Early flexion contractures of the elbow and interphalangeal joints of the last 4 fingers, and plantar flexion contractures of the ankles were constant findings. In contrast to Emery-Dreifuss muscular dystrophy (310300), contractures of the neck and spine were rarely seen (Mohire et al., 1988). Moreover, 4 of the 28 patients had congenital torticollis. The serum creatine phosphokinase activity was usually not elevated, and histopathologic findings were nonspecific. Genealogic investigations showed no relationship between these 3 families which had lived in the Netherlands from at least the beginning of the 18th century. </p><p>Schmalbruch et al. (1987) described a family in which members of both sexes in 3 generations had a benign form of congenital muscular dystrophy. Onset of symptoms was in early childhood and progression, if any, was slow. The proximal limb muscles, the sternocleidomastoid, and anterior tibial muscles were affected. One patient had torticollis and all had heel-cord shortening. There was no cardiomyopathy. Creatine kinase was elevated, and a histologic study showed necrotizing myopathy with pronounced regeneration and formation of aberrant myofibrils (ringbinden) and fibrosis. Leyten et al. (1986) described father and daughter with congenital muscular dystrophy. Mitochondrial abnormalities were found on muscle biopsy. </p><p>Merlini et al. (1994) described 2 families with early-onset, benign, autosomal dominant myopathy with contractures and reviewed 6 previously reported families with Bethlem myopathy. In both families, there were several instances of male-to-male transmission. Fifteen of the 21 examined members proved to have myopathy with contractures, although several of them were so mildly affected that they considered themselves asymptomatic. Electromyography demonstrated a myopathic pattern, and nerve conduction tests were normal. CT scan demonstrated unexpectedly severe fatty replacement of paravertebral muscles and relatively preserved gluteal muscles. Merlini et al. (1994) suggested that the hallmark of Bethlem myopathy was contractures of the last 4 fingers. Elbow contractures were also present in more than half the subjects, but the severity was not as great as that seen in Emery muscular dystrophy. There was no cardiac or respiratory involvement. </p><p>Tohyama et al. (1994) described an affected mother and daughter with contractures and mild proximal weakness. Muscle biopsy showed dystrophic features with evidence of fiber necrosis and regeneration. CT scanning demonstrated decreased volume of paravertebral muscles and low densities in various proximal muscles with essentially normal distal musculature. Tohyama et al. (1994) distinguished their cases from Bethlem myopathy because of dystrophic changes seen in muscle biopsy. However, the clinical presentation of both the Bethlem cases and these reported were similar. </p><p>Speer et al. (1995) noted that Bethlem myopathy shows a distribution of proximal muscle weakness similar to that observed in autosomal dominant limb-girdle muscular dystrophy (see, e.g., LGMDD1, 603511). They stated that it differs from most LGMDs in 2 ways: first, Bethlem myopathy presents with joint contractures, most commonly observed at the elbows, ankles, and neck; second, onset in Bethlem myopathy is in early childhood, whereas most dominant LGMDs show adult onset (Speer et al., 1995). </p><p>Jobsis et al. (1999) noted that Bethlem myopathy is a progressive disorder in adulthood, with many patients needing a wheelchair after age 50. </p><p>Haq et al. (1999) reported progressive respiratory failure caused by diaphragmatic paralysis in a patient with Bethlem myopathy. </p><p>Lampe and Bushby (2005) provided a review of collagen VI-related muscle disorders. The development of contractures is a hallmark of Bethlem myopathy. The contractures may appear and disappear in various joints during childhood, but nearly all patients eventually show flexion contractures of the fingers, wrists, elbows, and ankles, and these, in addition to weakness, contribute to disability. Lampe and Bushby (2005) pictured unusual skin features that may be present in some Bethlem myopathy patients, including follicular hyperkeratosis, keloid formation, and 'cigarette paper' scarring over the knees. </p>
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<strong>Inheritance</strong>
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<p>Bethlem myopathy-1A is inherited in an autosomal dominant pattern (Jobsis et al., 1996). </p>
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<strong>Mapping</strong>
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<p>In 6 Dutch families with Bethlem myopathy, 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>Diagnosis</strong>
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<p>Hicks et al. (2008) found that immunofluorescence labeling of collagen VI in skin biopsy-derived fibroblast cultures from patients suspected of having Bethlem myopathy was highly predictive of a COL6A mutation compared to immunofluorescence for collagen VI and basal lamina-located perlecan (HSPG2; 142461) in muscle samples. Abnormalities in the fibroblast labeling pattern of collagen VI were detected in more than 78% of genetically confirmed patients. Among 19 patients with an unknown genotype, the fibroblast technique providing a 75% positive predictive value, 100% sensitivity and negative predictive values, and specificity of 63%. </p>
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<strong>Clinical Management</strong>
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<p>Merlini et al. (2008) found that treatment of a patient with Bethlem myopathy and 4 UCMD patients with 2 divided doses of orally administered cyclosporin A resulted in decreased mitochondrial dysfunction and apoptosis in skeletal muscle biopsies 1 month later. Cellular signs of muscle regeneration were also observed. Clinical response could not be assessed because of the limited time frame, but the study provided a proof of principle and indicated that mitochondrial dysfunction plays a critical role in the pathogenesis of the disorder. </p>
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<strong>Molecular Genetics</strong>
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<p>In affected members of a kindred (family 2, originally reported by Bethlem and van Wijngaarden, 1976) with Bethlem myopathy, Jobsis et al. (1996) demonstrated a heterozygous missense mutation in the COL6A1 gene (G286V; 120220.0001). In affected members from 2 other kindreds, Jobsis et al. (1996) identified a heterozygous missense mutation in the COL6A2 gene (G250S, 120240.0001); see BTHLM1B (620725). 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, these observations suggested to Jobsis et al. (1996) a similar mechanism in Bethlem myopathy. </p><p>In affected members of an Italian family with Bethlem myopathy previously reported by Merlini et al. (1994), Vanegas et al. (2002) identified a heterozygous splice site mutation in the COL6A1 gene (120220.0008). </p><p>Lampe et al. (2005) sequenced all 3 COL6 genes from genomic DNA in 79 patients with Ullrich congenital muscular dystrophy (UCMD; 254090) or Bethlem myopathy, and found putative mutations in 1 of the COL6 genes in 62% of patients. Some patients showed changes in more than one of the COL6 genes, and some UCMD patients appeared to have dominant rather than recessive disease. Lampe et al. (2005) concluded that these findings may explain some or all of the cases of UCMD that are unlinked to the COL6 gene under a recessive model and noted that the large number of SNPs generated in this study may be of importance in determining the major phenotypic variability seen in this group of disorders. </p><p>Lucioli et al. (2005) identified 8 different mutations in the COL6A1 gene in 16 of 30 unrelated probands with a clinical diagnosis of Bethlem myopathy; 2 of the 30 probands had a mutation in the COL6A2 gene and the COL6A3 gene, respectively. The most common COL6A1 mutation was a splice site mutation (120220.0006). </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Brinas et al. (2010) classified 49 patients with muscular dystrophy due to mutations in 1 of the 3 COL6A genes into 3 clinical groups: 9 (18%) had a severe phenotype with contractures and never achieved ambulation, 26 (53%) had a moderate phenotype and were initially able to walk but tended to lose ambulation later in childhood, and 14 (29%) had a milder course and remained ambulatory at a mean age of 20 years. All patient fibroblasts showed absent or reduced COL6A secretion, with frequent intracellular retention, and the decreased levels correlated with increased disease severity. Genetic analysis showed equal distribution of mutations across the cohort: 17 (30%) in COL6A1, 26 (46%) in COL6A2, and 13 (23%) in COL6A3. Thirty patients (61%) had dominant de novo mutations, and 18 had recessive mutations. Fourteen patients (28.5%) had truncating mutations. Homozygous truncating mutations before or within the triple helix (TH) domain were associated with the most severe phenotypes. The moderate phenotype was associated with heterozygous mutations resulting in the skipping of part of the TH domains or affecting the glycine residue of the Gly-X-Y domain. RT-PCR analysis was helpful in defining the effect of splice site mutations. </p><p>Substitutions in the conserved Gly-X-Y motif in the triple helix (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies, accounting for almost one-third of all pathogenic mutations. Butterfield et al. (2013) analyzed genotype/phenotype correlations of 194 individuals with glycine substitutions in the TH domain of the COL6A1, COL6A2, or COL6A3 genes. The cohort included 97 newly reported cases and 97 published cases. In all 3 genes, 89% of the mutations clustered in the N-terminal regions before the 17th Gly-X-Y triplet (TH17). This important landmark is delineated by cysteine residues in the COL6A3 chain, which form disulfide bonds stabilizing tetramers. Patients with mutations inside the critical region of Gly-X-Y triplets 10-15 tended to have a more severe phenotype than those with mutations outside this critical region. However, identical glycine substitutions were associated with both severe and mild phenotypes. The most commonly observed mutation was G284R in the COL6A1 gene (120220.0012), found in 28 cases with variable phenotypes. Glycine substitutions in the TH domain were dominantly acting in 96% of cases, and recessive mutations tended to occur in the C-terminal end of the TH domain. Butterfield et al. (2013) concluded that the clustering of glycine substitutions in this region is not based on features of the primary sequence, but rather reflects a functional importance of this domain. </p>
</span>
<div>
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<h4>
<span class="mim-font">
<strong>Animal Model</strong>
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</h4>
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<span class="mim-text-font">
<p>Menazza et al. (2010) investigated whether reactive oxygen species (ROS) produced in mitochondria by monoamine oxidase (MAO) contribute to muscular dystrophy pathogenesis. Pargyline, an MAO inhibitor, reduced ROS accumulation along with a beneficial effect on the dystrophic phenotype of Col6a1 -/- mice, a model of Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD; 254090), and mdx mice, a model of Duchenne muscular dystrophy (310200). Oxidation of myofibrillar proteins, as probed by formation of disulfide crossbridges in tropomyosin (see 191010), was detected in both Col6a1 -/- and mdx muscles. Notably, pargyline significantly reduced myofiber apoptosis and ameliorated muscle strength in Col6a1 -/- mice. Menazza et al. (2010) concluded that there is a novel and determinant role of MAO in muscular dystrophies, adding evidence of the pivotal role of mitochondria and suggesting a therapeutic potential for MAO inhibition. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Gualandi et al. (2009); Speer et al. (1996)
</span>
<div>
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</div>
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
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</p>
</li>
<li>
<p class="mim-text-font">
Brinas, L., Richard, P., Quijano-Roy, S., Gartioux, C., Ledeuil, C., Lacene, E., Makri, S., Ferreiro, A., Maugenre, S., Topaloglu, H., Haliloglu, G., Penisson-Besnier, I., and 26 others.
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</p>
</li>
<li>
<p class="mim-text-font">
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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</p>
</li>
<li>
<p class="mim-text-font">
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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<li>
<p class="mim-text-font">
Jobsis, G. J., Boers, J. M., Barth, P. G., de Visser, M.
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[PubMed: 10219778]
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</p>
</li>
<li>
<p class="mim-text-font">
Jobsis, G. J., Bolhuis, P. A., Boers, J. M., Baas, F., Wolterman, R. A., Hensels, G. W., de Visser, M.
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[PubMed: 8618682]
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</p>
</li>
<li>
<p class="mim-text-font">
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: 8782832]
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</p>
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<p class="mim-text-font">
Lampe, A. K., Bushby, K. M. D.
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Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B.
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[Full Text: https://doi.org/10.1136/jmg.2004.023754]
</p>
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<p class="mim-text-font">
Leyten, Q. H., Gabreels, F. J. M., Joosten, E. M. G., Renier, W. O., Ter Laak, H. J., Ter Haar, B. G. A., Stadhouders, A. M.
<strong>An autosomal dominant type of congenital muscular dystrophy.</strong>
Brain Dev. 8: 533-537, 1986.
[PubMed: 3799922]
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</p>
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<p class="mim-text-font">
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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[PubMed: 15955946]
[Full Text: https://doi.org/10.1212/01.WNL.0000163990.00057.66]
</p>
</li>
<li>
<p class="mim-text-font">
Menazza, S., Blaauw, B., Tiepolo, T., Toniolo, L., Braghetta, P., Spolaore, B., Reggiani, C., Di Lisa, F., Bonaldo, P., Canton, M.
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</p>
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<p class="mim-text-font">
Merlini, L., Angelin, A., Tiepolo, T., Braghetta, P., Sabatelli, P., Zamparelli, A., Ferlini, A., Maraldi, N. M., Bonaldo, P., Bernardi, P.
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Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G.
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</p>
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</p>
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<p class="mim-text-font">
Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A.
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[PubMed: 8817344]
[Full Text: https://doi.org/10.1093/hmg/5.7.1043]
</p>
</li>
<li>
<p class="mim-text-font">
Speer, M. C., Yamaoka, L. H., Stajich, J., Lewis, K., Pericak-Vance, M. A., Stacy, R., Tandan, R., Fries, T. J.
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[PubMed: 8533815]
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</p>
</li>
<li>
<p class="mim-text-font">
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>
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[PubMed: 30055862]
[Full Text: https://doi.org/10.1016/j.nmd.2018.05.007]
</p>
</li>
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<p class="mim-text-font">
Tohyama, J., Inagaki, M., Nonaka, I.
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</p>
</li>
<li>
<p class="mim-text-font">
Vanegas, O. C., Zhang, R.-Z., Sabatelli, P., Lattanzi, G., Bencivenga, P., Giusti, B., Columbaro, M., Chu, M.-L., Merlini, L., Pepe, G.
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[PubMed: 11932968]
[Full Text: https://doi.org/10.1002/mus.10100]
</p>
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