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Entry
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- #607855 - MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT, 1A; MDC1A
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- OMIM
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<p>
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<span class="h4">#607855</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/607855"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#pathogenesis">Pathogenesis</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=284&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK97333/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/4985" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/lama2-related-muscular-dystrophy" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607855[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=258" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/589b5592-d85a-4d22-ba9e-7de723602241/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0110636" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/607855" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/results?search_type=advanced&omia_id=001619,002459" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0110636" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:607855" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 111503008, 787037000<br />
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<strong>ORPHA:</strong> 258<br />
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<strong>DO:</strong> 0110636<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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607855
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</span>
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</span>
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</div>
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT, 1A; MDC1A
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
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</div>
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|
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<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/6/842?start=-3&limit=10&highlight=842">
|
|
6q22.33
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, congenital, merosin deficient or partially deficient
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607855"> 607855 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<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">
|
|
LAMA2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/156225"> 156225 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/607855" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<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/607855" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/607855" 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 recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Ophthalmoplegia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16110005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16110005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000602" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000602</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000602" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000602</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 muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836141&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836141</a>, <a href="https://bioportal.bioontology.org/search?q=C3806467&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806467</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002747" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002747</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002747" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002747</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Feeding difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</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> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Kyphoscoliosis (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405771009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405771009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405772002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405772002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405773007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405773007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0600033&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0600033</a>, <a href="https://bioportal.bioontology.org/search?q=C0575158&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575158</a>, <a href="https://bioportal.bioontology.org/search?q=C0345392&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0345392</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002751</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0008453" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008453</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002751</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Limbs </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Joint contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7890003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7890003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/718.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.4</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/718.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034392" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034392</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">
|
|
|
|
- Muscle weakness, severe, axial and proximal predominance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807736&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807736</a>]</span> <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">[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 /> -
|
|
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
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Areflexia due to muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2750871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2750871</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br /> -
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Delayed motor development <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 /> -
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Myopathic changes seen on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276190&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276190</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 /> -
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Dystrophic changes seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279200&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279200</a>]</span><br /> -
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Absence of merosin in muscle <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842903&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842903</a>]</span><br /> -
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Absence of laminin alpha-2 chain in muscle <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842904&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842904</a>]</span><br /> -
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Increased endomysial connective tissue around muscle fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842905&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842905</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- White matter hypodensities seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807735&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807735</a>]</span><br /> -
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Abnormal cortical gyration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856019&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856019</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002536" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002536</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002536" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002536</a>]</span><br /> -
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Seizures (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
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Mental retardation (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Increased creatine kinase <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432352001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432352001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853034</a>, <a href="https://bioportal.bioontology.org/search?q=C0151576&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151576</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset at birth or early infancy<br /> -
|
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Ambulation usually not achieved<br /> -
|
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Partial laminin alpha-2 deficiency results in milder phenotype<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the laminin alpha-2 chain gene (LAMA2, <a href="/entry/156225#0001">156225.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is caused by homozygous or compound heterozygous mutation in the laminin alpha-2 gene (LAMA2; <a href="/entry/156225">156225</a>) on chromosome 6q22.</p><p>Biallelic mutation in the LAMA2 gene can also cause autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; <a href="/entry/618138">618138</a>), a less severe disorder.</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Merosin-deficient congenital muscular dystrophy is an autosomal recessive form of muscular dystrophy characterized by muscle weakness apparent at birth or in the first 6 months of life. Patients show hypotonia, poor suck and cry, and delayed motor development; most never achieve independent ambulation. Most patients also have periventricular white matter abnormalities on brain imaging, but mental retardation and/or seizures occur only rarely (summary by <a href="#30" class="mim-tip-reference" title="Xiong, H., Tan, D., Wang, S., Song, S., Yang, H., Gao, K., Liu, A., Jiao, H., Mao, B., Ding, J., Chang, X., Wang, J., Wu, Y., Yuan, Y., Jiang, Y., Zhang, F., Wu, H., Wu, X. <strong>Genotype/phenotype analysis in Chinese laminin-alpha-2 deficient congenital muscular dystrophy patients.</strong> Clin. Genet. 87: 233-243, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24611677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24611677</a>] [<a href="https://doi.org/10.1111/cge.12366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24611677">Xiong et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24611677" 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>
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<br />
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<div>
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p><a href="#28" class="mim-tip-reference" title="Tome, F. M. S., Evangelista, T., Leclerc, A., Sunada, Y., Manole, E., Estournet, B., Barois, A., Campbell, K. P., Fardeau, M. <strong>Congenital muscular dystrophy with merosin deficiency.</strong> C. R. Acad. Sci. III 317: 351-357, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8000914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8000914</a>]" pmid="8000914">Tome et al. (1994)</a> observed a specific absence of merosin, the laminin isoform in skeletal muscle, and a marked increase in endomysial connective tissue in 13 patients with congenital muscular dystrophy. <a href="#28" class="mim-tip-reference" title="Tome, F. M. S., Evangelista, T., Leclerc, A., Sunada, Y., Manole, E., Estournet, B., Barois, A., Campbell, K. P., Fardeau, M. <strong>Congenital muscular dystrophy with merosin deficiency.</strong> C. R. Acad. Sci. III 317: 351-357, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8000914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8000914</a>]" pmid="8000914">Tome et al. (1994)</a> investigated laminin because it is linked to the subsarcolemmal cytoskeleton by a large oligomeric complex of dystrophin (<a href="/entry/300377">300377</a>)-associated glycoproteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8000914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Sunada, Y., Edgar, T. S., Lotz, B. P., Rust, R. S., Campbell, K. P. <strong>Merosin-negative congenital muscular dystrophy associated with extensive brain abnormalities.</strong> Neurology 45: 2084-2089, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7501163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7501163</a>] [<a href="https://doi.org/10.1212/wnl.45.11.2084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7501163">Sunada et al. (1995)</a> described 2 unrelated Caucasian patients with merosin-negative congenital muscular dystrophy presenting with extensive brain abnormalities, including polymicrogyria and abnormal high-intensity signals in supratentorial white matter on T2-weighted brain MRIs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7501163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Mercuri, E., Muntoni, F., Berardinelli, A., Pennock, J., Sewry, C., Philpot, J., Dubowitz, V. <strong>Somatosensory and visual evoked potentials in congenital muscular dystrophy: correlation with MRI changes and muscle merosin status.</strong> Neuropediatrics 26: 3-7, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7791947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7791947</a>] [<a href="https://doi.org/10.1055/s-2007-979711" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7791947">Mercuri et al. (1995)</a> studied 17 unrelated individuals with congenital muscular dystrophy. All 7 of the merosin-deficient patients had abnormal white matter changes visible on MRI of the brain and abnormal somatosensory evoked potentials (SEP). In contrast, no MRI or SEP changes were found in the merosin-positive patients. In a following companion study, <a href="#11" class="mim-tip-reference" title="Mercuri, E., Dubowitz, L., Berardinelli, A., Pennock, J., Jongmans, M., Henderson, S., Muntoni, F., Sewry, C., Philpot, J., Dubowitz, V. <strong>Minor neurological and perceptuo-motor deficits in children with congenital muscular dystrophy: correlation with brain MRI changes.</strong> Neuropediatrics 26: 156-162, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7477754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7477754</a>] [<a href="https://doi.org/10.1055/s-2007-979746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7477754">Mercuri et al. (1995)</a> consistently found perceptuo-motor difficulties in those patients with abnormal MRI scans, but not in congenital muscular dystrophy children who were merosin positive and who had normal MRI scans. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7791947+7477754" 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="Hayashi, Y. K., Koga, R., Tsukahara, T., Ishii, H., Matsuishi, T., Yamashita, Y., Nonaka, I., Arahata, K. <strong>Deficiency of laminin alpha-2-chain mRNA in muscle in a patient with merosin-negative congenital muscular dystrophy.</strong> Muscle Nerve 18: 1027-1030, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643867</a>] [<a href="https://doi.org/10.1002/mus.880180918" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7643867">Hayashi et al. (1995)</a> identified 1 patient with merosin-negative congenital muscular dystrophy among 40 Japanese patients, both by immunocytochemical and biochemical examination. One 16-month-old girl had delayed motor milestones, generalized hypotonia, weakness, and diffuse low-density areas in the cerebral white matter. No laminin alpha-2 chain mRNA was detected by RT-PCR, but the presumed mutation in this gene was not delineated. Thus, <a href="#5" class="mim-tip-reference" title="Hayashi, Y. K., Koga, R., Tsukahara, T., Ishii, H., Matsuishi, T., Yamashita, Y., Nonaka, I., Arahata, K. <strong>Deficiency of laminin alpha-2-chain mRNA in muscle in a patient with merosin-negative congenital muscular dystrophy.</strong> Muscle Nerve 18: 1027-1030, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643867</a>] [<a href="https://doi.org/10.1002/mus.880180918" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7643867">Hayashi et al. (1995)</a> concluded that merosin-negative congenital muscular dystrophy does occur in Japan at a low frequency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7643867" 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="Shorer, Z., Philpot, J., Muntoni, F., Sewry, C., Dubowitz, V. <strong>Demyelinating peripheral neuropathy in merosin-deficient congenital muscular dystrophy.</strong> J. Child Neurol. 10: 472-475, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8576559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8576559</a>] [<a href="https://doi.org/10.1177/088307389501000610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8576559">Shorer et al. (1995)</a> demonstrated reduced motor nerve conduction velocities in 10 patients with merosin-negative congenital muscular dystrophy, but no reduction in nerve conduction velocity in 15 merosin-positive congenital muscular dystrophy cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8576559" 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>Several forms of congenital muscular dystrophy, namely, FCMD, muscle-eye-brain disease (<a href="/entry/253280">253280</a>), and Walker-Warburg syndrome (<a href="/entry/236670">236670</a>), have structural brain abnormalities and associated severe mental retardation. <a href="#20" class="mim-tip-reference" title="Philpot, J., Cowan, F., Pennock, J., Sewry, C., Dubowitz, V., Bydder, G., Muntoni, F. <strong>Merosin-deficient congenital muscular dystrophy: the spectrum of brain involvement on magnetic resonance imaging.</strong> Neuromusc. Disord. 9: 81-85, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220862</a>] [<a href="https://doi.org/10.1016/s0960-8966(98)00110-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10220862">Philpot et al. (1999)</a> demonstrated that a range of structural malformations can also be found in a substantial number of children with merosin-deficient CMD. They reported MRI studies of 14 children with merosin-deficient CMD. All 14 cases had white matter changes, which appeared after the first 6 months of life and persisted with time. The changes were diffuse and the oldest child scanned (14 years) also showed involvement of the U fibers. One child with moderate mental retardation and epilepsy, characterized mainly by complex partial seizures with atypical absences, which had been difficult to treat. MRI showed marked occipital agyria and pontocerebellar hypoplasia. The gyral pattern of the rest of the brain looked normal. Four other cases, all with normal intelligence, also had cerebellar hypoplasia with variable involvement of the pons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10220862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Taratuto, A. L., Lubieniecki, F., Diaz, D., Schultz, M., Ruggieri, V., Saccoliti, M., Dubrovsky, A. <strong>Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study.</strong> Neuromusc. Disord. 9: 86-94, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220863</a>] [<a href="https://doi.org/10.1016/s0960-8966(98)00112-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10220863">Taratuto et al. (1999)</a> reported clinical, biopsy, and autopsy findings in a merosin-deficient congenital muscular dystrophy infant with abnormal cortical gyration. The brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10220863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Pegoraro, E., Fanin, M., Trevisan, C. P., Angelini, C., Hoffman, E. P. <strong>A novel laminin alpha-2 isoform in severe laminin alpha-2 deficient congenital muscular dystrophy.</strong> Neurology 55: 1128-1134, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11071490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11071490</a>] [<a href="https://doi.org/10.1212/wnl.55.8.1128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11071490">Pegoraro et al. (2000)</a> reported a patient with a severe form of CMD caused by compound heterozygous mutations in the LAMA2 gene (<a href="/entry/156225#0011">156225.0011</a> and <a href="/entry/156225#0012">156225.0012</a>). She presented at birth with severe hypotonia and joint contractures. Motor milestones were severely delayed. She also had central nervous system involvement, including seizures, moderate mental retardation, ventricular dilatation, white matter abnormalities, and pachygyria. Muscle biopsy showed partial LAMA2 immunostaining, which was determined to be an alternatively spliced isoform lacking most of exon 31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11071490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Jones, K. J., Morgan, G., Johnston, H., Tobias, V., Ouvrier, R. A., Wilkinson, I., North, K. N. <strong>The expanding phenotype of laminin alpha-2 chain (merosin) abnormalities: case series and review.</strong> J. Med. Genet. 38: 649-657, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11584042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11584042</a>] [<a href="https://doi.org/10.1136/jmg.38.10.649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11584042">Jones et al. (2001)</a> reported a series of 5 patients with LAMA2 deficiency and reviewed published reports to characterize its phenotype. Only 1 of the 5 patients reported had a severe classic congenital muscular dystrophy phenotype. <a href="#8" class="mim-tip-reference" title="Jones, K. J., Morgan, G., Johnston, H., Tobias, V., Ouvrier, R. A., Wilkinson, I., North, K. N. <strong>The expanding phenotype of laminin alpha-2 chain (merosin) abnormalities: case series and review.</strong> J. Med. Genet. 38: 649-657, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11584042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11584042</a>] [<a href="https://doi.org/10.1136/jmg.38.10.649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11584042">Jones et al. (2001)</a> noted that of previously published cases, 12% had a later onset, slowly progressive muscle weakness more accurately designated 'limb-girdle muscular dystrophy.' Mental retardation was found in 6%, seizures in 8%, subclinical cardiac involvement in 3 to 35%, and neuronal migration defects in 4%. At least 25% of the reported cases had achieved independent ambulation. Three patients with LAMA2 deficiency were asymptomatic; 10 had normal MRI, 4 of whom had mutations in the LAMA2 gene. Between 10% and 20% of cases had maximum recorded creatine kinase of less than 1000 units per liter. LAMA2 gene mutations had been identified in 25% of cases, and 68% of these had the classic congenital muscular dystrophy phenotype. <a href="#8" class="mim-tip-reference" title="Jones, K. J., Morgan, G., Johnston, H., Tobias, V., Ouvrier, R. A., Wilkinson, I., North, K. N. <strong>The expanding phenotype of laminin alpha-2 chain (merosin) abnormalities: case series and review.</strong> J. Med. Genet. 38: 649-657, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11584042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11584042</a>] [<a href="https://doi.org/10.1136/jmg.38.10.649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11584042">Jones et al. (2001)</a> concluded that all dystrophic muscle biopsies, regardless of clinical phenotype, should be studied with antibodies to LAMA2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11584042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Xiong, H., Tan, D., Wang, S., Song, S., Yang, H., Gao, K., Liu, A., Jiao, H., Mao, B., Ding, J., Chang, X., Wang, J., Wu, Y., Yuan, Y., Jiang, Y., Zhang, F., Wu, H., Wu, X. <strong>Genotype/phenotype analysis in Chinese laminin-alpha-2 deficient congenital muscular dystrophy patients.</strong> Clin. Genet. 87: 233-243, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24611677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24611677</a>] [<a href="https://doi.org/10.1111/cge.12366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24611677">Xiong et al. (2015)</a> reported the clinical features and genetic analysis of 43 children or teens, mostly of Han Chinese descent, with congenital muscular dystrophy and LAMA2 deficiency apparent on skeletal muscle biopsy. Most (29 patients) had hypotonia and weak cry apparent at birth, whereas the remaining patients showed these symptoms and delayed motor development within the first 6 months of life. Thirty-eight patients never achieved independent ambulation, and 5 had mild muscle weakness with impaired gait. Ophthalmoplegia was identified in 23 patients. Brain imaging of all patients showed abnormal T2 intensities in the bilateral periventricular white matter with sparing of the corpus callosum, internal capsule, cerebellum, and brainstem. Eight patients with mental retardation and/or epilepsy had more diffuse white matter abnormalities. Cortical malformations were not observed. Genetic analysis identified biallelic mutations or deletions in the LAMA2 gene; there were no apparent genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24611677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#15" class="mim-tip-reference" title="Naom, I., D'Alessandro, M., Sewry, C., Ferlini, A., Topaloglu, H., Helbling-Leclerc, A., Guicheney, P., Schwartz, K., Akcoren, Z., Dubowitz, V., Muntoni, F. <strong>The role of immunocytochemistry and linkage analysis in the prenatal diagnosis of merosin-deficient congenital muscular dystrophy.</strong> Hum. Genet. 99: 535-540, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9099847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9099847</a>] [<a href="https://doi.org/10.1007/s004390050402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9099847">Naom et al. (1997)</a> concluded that immunocytochemical analysis of the laminin alpha-2 chain in the trophoblast can detect abnormalities in affected fetuses and give normal results in unaffected and carrier fetuses. Nonetheless, they recommended that linkage analysis of the LAMA2 locus also be studied in all cases for the prenatal diagnosis of merosin-deficient congenital muscular dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9099847" 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>Using tightly linked informative polymorphic microsatellite markers, <a href="#1" class="mim-tip-reference" title="D'Alessandro, M., Naom, I., Ferlini, A., Sewry, C., Dubowitz, V., Muntoni, F. <strong>Is there selection in favour of heterozygotes in families with merosin-deficient congenital muscular dystrophy?</strong> Hum. Genet. 105: 308-313, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10543397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10543397</a>] [<a href="https://doi.org/10.1007/s004399900093" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10543397">D'Alessandro et al. (1999)</a> investigated the pattern of inheritance of the haplotypes associated with the mutant allele in 29 informative merosin-deficient families. This allowed them to identify heterozygous individuals from normal homozygotes, who are clinically, pathologically, and biochemically indistinguishable. By linkage analysis, they found a statistically significant increase in the number of heterozygous individuals carrying either the paternal or the maternal haplotypes associated with the mutant allele. They raised the question of whether there is selection in favor of heterozygotes in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10543397" 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="#7" class="mim-tip-reference" title="Hillaire, D., Leclerc, A., Faure, S., Topaloglu, H., Chiannilkulchai, N., Guicheney, P., Grinas, L., Legos, P., Philpot, J., Evangelista, T., Routon, M.-C., Mayer, M., Pellissier, J.-F., Estournet, B., Barois, A., Hentati, F., Feingold, N., Beckmann, J. S., Dubowitz, V., Tome, F. M. S., Fardeau, M. <strong>Localization of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping.</strong> Hum. Molec. Genet. 3: 1657-1661, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7833925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7833925</a>] [<a href="https://doi.org/10.1093/hmg/3.9.1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7833925">Hillaire et al. (1994)</a> demonstrated by homozygosity mapping that merosin-negative congenital muscular dystrophy is linked to a 16-cM region of 6q2 where the laminin M gene maps. In 3 consanguineous, merosin-positive congenital muscular dystrophy families, they found no linkage to 6q2 or to 9q31-q33 where the FCMD locus maps. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7833925" 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 2 families with congenital merosin-deficient muscular dystrophy, <a href="#6" class="mim-tip-reference" title="Helbling-Leclerc, A., Zhang, X., Topaloglu, H., Cruaud, C., Tesson, F., Weissenbach, J., Tome, F. M. S., Schwartz, K., Fardeau, M., Tryggvason, K., Guicheney, P. <strong>Mutations in the laminin alpha-2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy.</strong> Nature Genet. 11: 216-218, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550355</a>] [<a href="https://doi.org/10.1038/ng1095-216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550355">Helbling-Leclerc et al. (1995)</a> identified 2 different homozygous mutations (<a href="/entry/156225#0001">156225.0001</a>-<a href="/entry/156225#0002">156225.0002</a>) in the LAMA2 gene. They suggested that 'the extracellular location of laminin-2 may allow new therapeutic strategies to restore its presence at the periphery of the muscle fibres and to modify the severe course of this very disabling disease.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550355" 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>Complete LAMA2 deficiency causes approximately half of CMD cases. <a href="#27" class="mim-tip-reference" title="Tezak, Z., Prandini, P., Boscaro, M., Marin, A., Devaney, J., Marino, M., Fanin, M., Trevisan, C. P., Park, J., Tyson, W., Finkel, R., Garcia, C., Angelini, C., Hoffman, E. P., Pegoraro, E. <strong>Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha-2 (LAMA2) deficiency.</strong> Hum. Mutat. 21: 103-111, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552556</a>] [<a href="https://doi.org/10.1002/humu.10157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552556">Tezak et al. (2003)</a> noted that many loss-of-function mutations had been reported in these severe, neonatal-onset patients, but only missense mutations had been found in milder CMD with partial LAMA2 deficiency. They studied 9 patients with CMD who showed abnormal white matter signal on brain MRI and partial deficiency of LAMA2 on immunofluorescence of muscle biopsy, and identified changes in the LAMA2 sequence in 6. Five of the 6 changes were novel; these included 3 missense changes (see, e.g., <a href="/entry/156225#0009">156225.0009</a>-<a href="/entry/156225#0010">156225.0010</a>) and 2 splice site mutations. The finding of partial LAMA2 deficiency by immunostaining was not specific for carriers of a LAMA2 gene mutation, as only 2 patients showed clear causative mutations, and an additional 3 showed possible mutations. The clinical presentation and disease progression were the same in LAMA2 mutation-positive and mutation-negative CMD patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Di Blasi, C., Piga, D., Brioschi, P., Moroni, I., Pini, A., Ruggieri, A., Zanotti, S., Uziel, G., Jarre, L., Della Giustina, E., Scuderi, C., Jonsrud, C., . Mantegazza, R., Morandi, L., Mora, M. <strong>LAMA2 gene analysis in congenital muscular dystrophy: new mutations, prenatal diagnosis, and founder effect.</strong> Arch. Neurol. 62: 1582-1586, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16216942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16216942</a>] [<a href="https://doi.org/10.1001/archneur.62.10.1582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16216942">Di Blasi et al. (2005)</a> identified 10 LAMA2 mutations, including 9 novel mutations, in 10 of 15 patients with congenital muscular dystrophy and undetectable or greatly reduced muscle expression of LAMA2 protein. All mutation-positive patients had generalized hypotonia and severe weakness from birth, and all had abnormal MRI changes. One founder mutation (<a href="/entry/156225#0013">156225.0013</a>) was identified and determined to originate from Albania. Two of the 5 patients without detectable LAMA2 mutations and who also did not have white matter changes were found to have mutations in the FKRP gene (<a href="/entry/606596">606596</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16216942" 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="Oliveira, J., Santos, R., Soares-Silva, I., Jorge, P., Vieira, E., Oliveira, M. E., Moreira, A., Coelho, T., Ferreira, J. C., Fonseca, M. J., Barbosa, C., Prats, J., Ariztegui, M. L., Martins, M. L., Moreno, T., Heinimann, K., Barbot, C., Pascual-Pascual, S. I., Cabral, A., Fineza, I., Santos, M., Bronze-da-Rocha, E. <strong>LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients.</strong> Clin. Genet. 74: 502-512, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18700894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18700894</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01068.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18700894">Oliveira et al. (2008)</a> identified 18 different mutations in the LAMA2 gene, including 14 novel mutations, in 50 (96%) of 52 disease alleles in all 26 patients with a clinical presentation suggestive of MDC1A. Only heterozygous mutations were identified in 2 patients. Ten (31%) patients carried a common 5-kb deletion encompassing exon 56 of the LAMA2 gene (<a href="/entry/156225#0015">156225.0015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18700894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a comprehensive mutation update on LAMA2 mutations, <a href="#17" class="mim-tip-reference" title="Oliveira, J., Gruber, A., Cardoso, M., Taipa, R., Fineza, I., Goncalves, A., Laner, A., Winder, T. L., Schroeder, J., Rath, J., Oliveira, M. E., Vieira, E., and 11 others. <strong>LAMA2 gene mutation update: toward a more comprehensive picture of the laminin-alpha-2 variome and its related phenotypes.</strong> Hum. Mutat. 39: 1314-1337, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055037</a>] [<a href="https://doi.org/10.1002/humu.23599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055037">Oliveira et al. (2018)</a> stated that the most frequently reported genotypes are variants that create premature termination codons (PTC) in both disease alleles, are associated with complete deficiency of laminin in muscle biopsy, and cause a severe, congenital muscular dystrophy (MDC1A). In contrast, missense variants, which are present in a smaller number of cases, usually correlate with partial laminin deficiency in muscle biopsy, and cause a milder, later-onset disorder (LGMDR23). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055037" 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="#25" class="mim-tip-reference" title="Taniguchi, M., Kurahashi, H., Noguchi, S., Sese, J., Okinaga, T., Tsukahara, T., Guicheney, P., Ozono, K., Nishino, I., Morishita, S., Toda, T. <strong>Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-alpha-2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?</strong> Biochem. Biophys. Res. Commun. 342: 489-502, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16487936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16487936</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.12.224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16487936">Taniguchi et al. (2006)</a> performed histologic examination and cDNA microarray analysis of skeletal muscle biopsy specimens from 4 patients with FCMD and 1 with MDC1A at various ages during childhood. Histologic examination showed dystrophic features, fiber size variation, prominent interstitial tissue, and adipose tissue proliferation. Inflammation, necrosis, and regeneration of muscle fibers were less apparent, especially compared to biopsies from patients with Duchenne muscular dystrophy (DMD; <a href="/entry/310200">310200</a>). FCMD and MDC1A samples showed increased expression of extracellular matrix genes, such as COL3A1 (<a href="/entry/120180">120180</a>), THBS4 (<a href="/entry/600715">600715</a>), and OSF2 (POSTN; <a href="/entry/608777">608777</a>), whereas there was downregulation of genes encoding mature muscle components, including MYH7 (<a href="/entry/160760">160760</a>), TCAP (<a href="/entry/604488">604488</a>), DES (<a href="/entry/125660">125660</a>), and MYH1 (<a href="/entry/160730">160730</a>). Upregulation of gene expression occurred predominantly in muscle fibers and only slightly in fibroblasts. In contrast, a previous microarray analysis of DMD muscle (<a href="#16" class="mim-tip-reference" title="Noguchi, S., Tsukahara, T., Fujita, M., Kurokawa, R., Tachikawa, M., Toda, T., Tsujimoto, A., Arahata, K., Nishino, I. <strong>cDNA microarray analysis of individual Duchenne muscular dystrophy patients.</strong> Hum. Molec. Genet. 12: 595-600, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12620965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12620965</a>]" pmid="12620965">Noguchi et al., 2003</a>) reported upregulation of genes encoding muscle components, reflecting enhanced active muscle fiber regeneration following degeneration in DMD. <a href="#25" class="mim-tip-reference" title="Taniguchi, M., Kurahashi, H., Noguchi, S., Sese, J., Okinaga, T., Tsukahara, T., Guicheney, P., Ozono, K., Nishino, I., Morishita, S., Toda, T. <strong>Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-alpha-2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?</strong> Biochem. Biophys. Res. Commun. 342: 489-502, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16487936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16487936</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.12.224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16487936">Taniguchi et al. (2006)</a> suggested that the primary pathologic feature of FCMD and MDC1A is interstitial fibrosis without muscle degeneration and regeneration, which distinguishes these disorders from DMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16487936+12620965" 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>Bax (<a href="/entry/600040">600040</a>)-mediated muscle cell death is a significant contributor to the severe neuromuscular pathology seen in the Lama2-null mouse model of MDC1A. <a href="#29" class="mim-tip-reference" title="Vishnudas, V. K., Miller, J. B. <strong>Ku70 regulates Bax-mediated pathogenesis in laminin-alpha-2-deficient human muscle cells and mouse models of congenital muscular dystrophy.</strong> Hum. Molec. Genet. 18: 4467-4477, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19692349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19692349</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19692349[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19692349">Vishnudas and Miller (2009)</a> analyzed molecular mechanisms of Bax regulation in normal and LAMA2-deficient muscles and cells, including myogenic cells from MDC1A patients. In mouse myogenic cells, Bax coimmunoprecipitated with the multifunctional protein Ku70 (XRCC6; <a href="/entry/152690">152690</a>). In addition, cell-permeable pentapeptides designed from Ku70, termed Bax-inhibiting peptides (BIPs), inhibited staurosporine-induced Bax translocation and cell death in mouse myogenic cells. Acetylation of Ku70, which can inhibit binding to Bax and can be an indicator of increased susceptibility to cell death, was more abundant in Lama2-null mouse muscles than in normal mouse muscles. Myotubes formed in culture from human LAMA2-deficient patient myoblasts produced high levels of activated caspase-3 (CASP3; <a href="/entry/600636">600636</a>) when grown on poly-L-lysine, but not when grown on a LAMA2-containing substrate or when treated with BIPs. Cytoplasmic Ku70 in human LAMA2-deficient myotubes was both reduced in amount and more highly acetylated than in normal myotubes. <a href="#29" class="mim-tip-reference" title="Vishnudas, V. K., Miller, J. B. <strong>Ku70 regulates Bax-mediated pathogenesis in laminin-alpha-2-deficient human muscle cells and mouse models of congenital muscular dystrophy.</strong> Hum. Molec. Genet. 18: 4467-4477, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19692349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19692349</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19692349[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19692349">Vishnudas and Miller (2009)</a> concluded that increased susceptibility to cell death appears to be an intrinsic property of human LAMA2-deficient myotubes and that Ku70 is a regulator of Bax-mediated pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19692349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The classic mouse muscular dystrophy strain, dy, was described by <a href="#13" class="mim-tip-reference" title="Michelson, A. M., Russell, E. S., Harman, P. J. <strong>Dystrophia muscularis: a hereditary primary myopathy in the house mouse.</strong> Proc. Nat. Acad. Sci. 41: 1079-1084, 1955.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16589799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16589799</a>] [<a href="https://doi.org/10.1073/pnas.41.12.1079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16589799">Michelson et al. (1955)</a>. A large literature on the morphologic and biochemical characteristics of the mutation accumulated thereafter. The homozygous mice showed severe progressive muscular dystrophy. In addition, these mice were smaller than their littermates and died between 2 and 6 months of unknown cause. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16589799" 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="#31" class="mim-tip-reference" title="Xu, H., Christmas, P., Wu, X.-R., Wewer, U. M., Engvall, E. <strong>Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.</strong> Proc. Nat. Acad. Sci. 91: 5572-5576, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8202529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8202529</a>] [<a href="https://doi.org/10.1073/pnas.91.12.5572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8202529">Xu et al. (1994)</a> found that the heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting in dy/dy mice, but was expressed normally in heterozygous and wildtype nondystrophic mice. Immunofluorescence confirmed the presence of other major basement membrane proteins in the dystrophic mice. Very low levels of M-laminin heavy chain mRNA were detected by Northern blotting of muscle and heart tissue from dy/dy mice, suggesting that M-laminin heavy chain mRNA may be produced at very low levels or is unstable. Since the gene for the M-laminin heavy chain maps to mouse chromosome 10 in the same region as does the dy locus, <a href="#32" class="mim-tip-reference" title="Xu, H., Wu, X.-R., Wewer, U. M., Engvall, E. <strong>Murine muscular dystrophy caused by a mutation in the laminin alpha-2 (Lama2) gene.</strong> Nature Genet. 8: 297-302, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7874173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7874173</a>] [<a href="https://doi.org/10.1038/ng1194-297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7874173">Xu et al. (1994)</a> suggested that mutation in that gene causes the muscular dystrophy. Preliminary studies using Southern blotting showed that the M-chain gene was not deleted in the dystrophic mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7874173+8202529" 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="#23" class="mim-tip-reference" title="Sunada, Y., Bernier, S. M., Kozak, C. A., Yamada, Y., Campbell, K. P. <strong>Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locus.</strong> J. Biol. Chem. 269: 13729-13732, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188645</a>]" pmid="8188645">Sunada et al. (1994)</a> demonstrated that merosin is a native ligand for alpha-dystroglycan, an extracellular component of the dystrophin-glycoprotein complex, and that the gene encoding it in the mouse, Lamm, maps to the same region of chromosome 10 in which the dy locus had been mapped. Analysis of merosin expression in dy mice demonstrated a specific deficiency in skeletal muscle, cardiac muscle, and peripheral nerve. The dysmyelination in the dorsal and ventral nerve roots probably relates to the normal expression of merosin in Schwann cells as well as in muscle basement membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8188645" 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="#32" class="mim-tip-reference" title="Xu, H., Wu, X.-R., Wewer, U. M., Engvall, E. <strong>Murine muscular dystrophy caused by a mutation in the laminin alpha-2 (Lama2) gene.</strong> Nature Genet. 8: 297-302, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7874173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7874173</a>] [<a href="https://doi.org/10.1038/ng1194-297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7874173">Xu et al. (1994)</a> identified the molecular basis of a dy allele, called dy(2J), by detecting a mutation in the laminin alpha-2 chain gene. The G-to-A mutation in a splice site consensus sequence caused abnormal splicing and expression of multiple mRNAs. One mRNA was translated into an alpha-2 polypeptide with a deletion in domain VI. The truncated protein apparently lacked important qualities of the wildtype protein and was unable to provide sufficient muscle stability. <a href="#32" class="mim-tip-reference" title="Xu, H., Wu, X.-R., Wewer, U. M., Engvall, E. <strong>Murine muscular dystrophy caused by a mutation in the laminin alpha-2 (Lama2) gene.</strong> Nature Genet. 8: 297-302, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7874173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7874173</a>] [<a href="https://doi.org/10.1038/ng1194-297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7874173">Xu et al. (1994)</a> stated the following: 'It is becoming increasingly clear that muscular dystrophy may be caused by mutations in a number of proteins involved in stabilizing the muscle cell membrane, including attachment of the muscle cell to the extracellular matrix. In this respect, parallels may be found in the mutations causing skin blistering diseases, epidermolysis bullosa.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7874173" 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="Kuang, W., Xu, H., Vachon, P. H., Liu, L., Loechel, F., Wewer, U. M., Engvall, E. <strong>Merosin-deficient congenital muscular dystrophy: partial genetic correction in two mouse models.</strong> J. Clin. Invest. 102: 844-852, 1998. Note: Erratum: J. Clin. Invest. 102: following 1275, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9710454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9710454</a>] [<a href="https://doi.org/10.1172/JCI3705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9710454">Kuang et al. (1998)</a> studied mouse models of merosin-deficient congenital muscular dystrophy (MCMD), both spontaneous mutant mice and null mutant mice created by homologous recombination in embryonic stem cells. In mice with complete or partial deficiency of merosin, they expressed a human LAMA2 transgene under the regulation of a muscle-specific creatine kinase promoter. The transgene restored the synthesis and localization of merosin in skeletal muscle, and greatly improved muscle morphology and integrity and the health and longevity of the mice. However, the transgenic mice shared with the nontransgenic dystrophic mice a progressive lameness of hind legs, suggestive of a nerve defect. These results indicated that the absence of merosin in tissues other than muscle, such as nervous tissue, is a critical component of MCMD. Future gene therapy of human MCMD, and perhaps of other forms of muscular dystrophy, may require restoration of a defective gene product in multiple tissues. The observation had previously been made that a characteristic of human MCMD and merosin-deficient muscular dystrophy in mice is that motor nerves are fully myelinated, suggesting that merosin may be important in nervous tissue in addition to muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9710454" 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>Aiming to restore muscle function to a mouse model of LAMA2 deficiency, <a href="#14" class="mim-tip-reference" title="Moll, J., Barzaghi, P., Lin, S., Bezakova, G., Lochmuller, H., Engvall, E., Muller, U., Ruegg, M. A. <strong>An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy.</strong> Nature 413: 302-307, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565031</a>] [<a href="https://doi.org/10.1038/35095054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11565031">Moll et al. (2001)</a> designed a minigene of agrin (<a href="/entry/103320">103320</a>), a protein known for its role in the formation of the neuromuscular junction. <a href="#14" class="mim-tip-reference" title="Moll, J., Barzaghi, P., Lin, S., Bezakova, G., Lochmuller, H., Engvall, E., Muller, U., Ruegg, M. A. <strong>An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy.</strong> Nature 413: 302-307, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565031</a>] [<a href="https://doi.org/10.1038/35095054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11565031">Moll et al. (2001)</a> demonstrated that this mini-agrin, which binds to basement membrane and to alpha-dystroglycan (<a href="/entry/128239">128239</a>), a member of the dystrophin-glycoprotein complex, amends muscle pathology by a mechanism that includes agrin-mediated stabilization of alpha-dystroglycan and the laminin alpha-5 chain (<a href="/entry/601033">601033</a>). <a href="#14" class="mim-tip-reference" title="Moll, J., Barzaghi, P., Lin, S., Bezakova, G., Lochmuller, H., Engvall, E., Muller, U., Ruegg, M. A. <strong>An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy.</strong> Nature 413: 302-307, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11565031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11565031</a>] [<a href="https://doi.org/10.1038/35095054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11565031">Moll et al. (2001)</a> concluded that their data provided in vivo evidence that a nonhomologous protein in combination with rational protein design can be used to devise therapeutic tools that may restore muscle function in human muscular dystrophies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11565031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review, <a href="#21" class="mim-tip-reference" title="Shelton, G. D., Engvall, E. <strong>Canine and feline models of human inherited muscle diseases.</strong> Neuromusc. Disord. 15: 127-138, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15694134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15694134</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15694134">Shelton and Engvall (2005)</a> stated that animal models of LAMA2 deficiency had been described in the Brittany-Springer spaniel mixed breed dog, and in several cat breeds, including Siamese, Maine Coon cat, and a domestic shorthair mixed breed. The authors noted that the findings of laminin-alpha-2 deficiency in mixed breeds suggests that mutations are present in the gene pools of several breeds of dogs and cats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15694134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Girgenrath, M., Beermann, M. L., Vishnudas, V. K., Homma, S., Miller, J.B. <strong>Pathology is alleviated by doxycycline in a laminin-alpha2-null model of congenital muscular dystrophy.</strong> Ann. Neurol. 65: 47-56, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19086074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19086074</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19086074[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21523" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19086074">Girgenrath et al. (2009)</a> found that treatment of Lama2-null mice with either minocycline or doxycycline, which inhibit apoptosis, showed clinical and pathologic improvement. Treated mice had increased life span, improved growth, and delayed onset of hindlimb paralysis. Muscles derived from the treated mice were larger than untreated mice, showed decreased inflammation, increased Akt (<a href="/entry/164730">164730</a>) phosphorylation, and decreased markers of apoptosis, such as Bax (<a href="/entry/600040">600040</a>) and caspase-3 (CASP3; <a href="/entry/600636">600636</a>). The findings indicated that increased apoptosis is a major pathogenic mechanism in LAMA2 deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19086074" 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>Transgenic overexpression of Lama1 (<a href="/entry/150320">150320</a>) had been shown to ameliorate muscle wasting and paralysis in mouse models of MDC1A (<a href="#3" class="mim-tip-reference" title="Gawlik, K., Miyagoe-Suzuki, Y., Ekblom, P., Takeda, S., Durbeej, M. <strong>Laminin alpha-1 chain reduces muscular dystrophy in laminin alpha-2 chain deficient mice.</strong> Hum. Molec. Genet. 13: 1775-1784, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15213105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15213105</a>] [<a href="https://doi.org/10.1093/hmg/ddh190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15213105">Gawlik et al., 2004</a>). However, the large size of Lama1 exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy. <a href="#9" class="mim-tip-reference" title="Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A., Cohn, R. D. <strong>A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene.</strong> Nature 572: 125-130, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31341277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31341277</a>] [<a href="https://doi.org/10.1038/s41586-019-1430-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31341277">Kemaladewi et al. (2019)</a> modulated expression of Lama1 in the dy(2j)/dy(2j) mouse model of MDC1a using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators, and single-guide RNAs that target the Lama1 promoter. When presymptomatic mice were treated, Lama1 was upregulated in skeletal muscles and peripheral nerves, which prevented muscle fibrosis and paralysis. Although it had been hypothesized that fibrotic changes in skeletal muscle are irreversible, <a href="#9" class="mim-tip-reference" title="Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A., Cohn, R. D. <strong>A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene.</strong> Nature 572: 125-130, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31341277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31341277</a>] [<a href="https://doi.org/10.1038/s41586-019-1430-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31341277">Kemaladewi et al. (2019)</a> showed that dystrophic features and disease progression were improved and reversed when the treatment was initiated in symptomatic dy(2j)/dy(2j) mice with hindlimb paralysis and muscle fibrosis. <a href="#9" class="mim-tip-reference" title="Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A., Cohn, R. D. <strong>A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene.</strong> Nature 572: 125-130, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31341277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31341277</a>] [<a href="https://doi.org/10.1038/s41586-019-1430-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31341277">Kemaladewi et al. (2019)</a> concluded that their data demonstrated the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which opened the possibility of mutation-independent treatment for patients with MDC1A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15213105+31341277" 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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D'Alessandro, M., Naom, I., Ferlini, A., Sewry, C., Dubowitz, V., Muntoni, F.
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[<a href="https://doi.org/10.1007/s004399900093" target="_blank">Full Text</a>]
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Di Blasi, C., Piga, D., Brioschi, P., Moroni, I., Pini, A., Ruggieri, A., Zanotti, S., Uziel, G., Jarre, L., Della Giustina, E., Scuderi, C., Jonsrud, C., . Mantegazza, R., Morandi, L., Mora, M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16216942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16216942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16216942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Laminin alpha-1 chain reduces muscular dystrophy in laminin alpha-2 chain deficient mice.</strong>
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Hum. Molec. Genet. 13: 1775-1784, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15213105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15213105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15213105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Pathology is alleviated by doxycycline in a laminin-alpha2-null model of congenital muscular dystrophy.</strong>
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Ann. Neurol. 65: 47-56, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10220862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0960-8966(98)00110-2" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2004.10.019" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1177/088307389501000610" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.45.11.2084" target="_blank">Full Text</a>]
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Taniguchi, M., Kurahashi, H., Noguchi, S., Sese, J., Okinaga, T., Tsukahara, T., Guicheney, P., Ozono, K., Nishino, I., Morishita, S., Toda, T.
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[<a href="https://doi.org/10.1016/j.bbrc.2005.12.224" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0960-8966(98)00112-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.10157" target="_blank">Full Text</a>]
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Vishnudas, V. K., Miller, J. B.
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Hum. Molec. Genet. 18: 4467-4477, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19692349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19692349</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19692349[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=19692349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp399" target="_blank">Full Text</a>]
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Xiong, H., Tan, D., Wang, S., Song, S., Yang, H., Gao, K., Liu, A., Jiao, H., Mao, B., Ding, J., Chang, X., Wang, J., Wu, Y., Yuan, Y., Jiang, Y., Zhang, F., Wu, H., Wu, X.
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Xu, H., Christmas, P., Wu, X.-R., Wewer, U. M., Engvall, E.
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<strong>Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.</strong>
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Xu, H., Wu, X.-R., Wewer, U. M., Engvall, E.
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<strong>Murine muscular dystrophy caused by a mutation in the laminin alpha-2 (Lama2) gene.</strong>
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Nature Genet. 8: 297-302, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7874173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7874173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7874173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1194-297" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 01/06/2020
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Cassandra L. Kniffin - updated : 10/04/2018<br>Cassandra L. Kniffin - updated : 3/25/2015<br>George E. Tiller - updated : 10/28/2010<br>Cassandra L. Kniffin - updated : 1/5/2010<br>Cassandra L. Kniffin - updated : 2/23/2009<br>Cassandra L. Kniffin - updated : 10/9/2006<br>Cassandra L. Kniffin - updated : 7/12/2006<br>Cassandra L. Kniffin - updated : 6/5/2006<br>Cassandra L. Kniffin - updated : 1/11/2006
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Cassandra L. Kniffin : 6/5/2003
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carol : 04/02/2021
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alopez : 01/06/2020<br>carol : 10/08/2018<br>carol : 10/05/2018<br>ckniffin : 10/04/2018<br>alopez : 08/04/2015<br>alopez : 3/30/2015<br>mcolton : 3/26/2015<br>ckniffin : 3/25/2015<br>carol : 2/23/2015<br>carol : 3/21/2013<br>ckniffin : 11/15/2010<br>wwang : 11/5/2010<br>terry : 10/28/2010<br>wwang : 1/21/2010<br>ckniffin : 1/5/2010<br>wwang : 7/21/2009<br>wwang : 4/2/2009<br>ckniffin : 2/23/2009<br>wwang : 10/18/2006<br>ckniffin : 10/9/2006<br>wwang : 8/3/2006<br>ckniffin : 7/12/2006<br>wwang : 6/23/2006<br>ckniffin : 6/5/2006<br>wwang : 1/18/2006<br>ckniffin : 1/11/2006<br>ckniffin : 6/12/2003<br>carol : 6/10/2003<br>ckniffin : 6/6/2003
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<strong>#</strong> 607855
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MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT, 1A; MDC1A
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MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT
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Other entities represented in this entry:
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MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY, INCLUDED
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<strong>SNOMEDCT:</strong> 111503008, 787037000;
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<strong>ORPHA:</strong> 258;
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<strong>DO:</strong> 0110636;
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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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<span class="mim-font">
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6q22.33
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Muscular dystrophy, congenital, merosin deficient or partially deficient
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607855
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Autosomal recessive
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<span class="mim-font">
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3
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LAMA2
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156225
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is caused by homozygous or compound heterozygous mutation in the laminin alpha-2 gene (LAMA2; 156225) on chromosome 6q22.</p><p>Biallelic mutation in the LAMA2 gene can also cause autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; 618138), a less severe disorder.</p>
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<strong>Description</strong>
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<p>Merosin-deficient congenital muscular dystrophy is an autosomal recessive form of muscular dystrophy characterized by muscle weakness apparent at birth or in the first 6 months of life. Patients show hypotonia, poor suck and cry, and delayed motor development; most never achieve independent ambulation. Most patients also have periventricular white matter abnormalities on brain imaging, but mental retardation and/or seizures occur only rarely (summary by Xiong et al., 2015). </p>
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<strong>Clinical Features</strong>
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<p>Tome et al. (1994) observed a specific absence of merosin, the laminin isoform in skeletal muscle, and a marked increase in endomysial connective tissue in 13 patients with congenital muscular dystrophy. Tome et al. (1994) investigated laminin because it is linked to the subsarcolemmal cytoskeleton by a large oligomeric complex of dystrophin (300377)-associated glycoproteins. </p><p>Sunada et al. (1995) described 2 unrelated Caucasian patients with merosin-negative congenital muscular dystrophy presenting with extensive brain abnormalities, including polymicrogyria and abnormal high-intensity signals in supratentorial white matter on T2-weighted brain MRIs. </p><p>Mercuri et al. (1995) studied 17 unrelated individuals with congenital muscular dystrophy. All 7 of the merosin-deficient patients had abnormal white matter changes visible on MRI of the brain and abnormal somatosensory evoked potentials (SEP). In contrast, no MRI or SEP changes were found in the merosin-positive patients. In a following companion study, Mercuri et al. (1995) consistently found perceptuo-motor difficulties in those patients with abnormal MRI scans, but not in congenital muscular dystrophy children who were merosin positive and who had normal MRI scans. </p><p>Hayashi et al. (1995) identified 1 patient with merosin-negative congenital muscular dystrophy among 40 Japanese patients, both by immunocytochemical and biochemical examination. One 16-month-old girl had delayed motor milestones, generalized hypotonia, weakness, and diffuse low-density areas in the cerebral white matter. No laminin alpha-2 chain mRNA was detected by RT-PCR, but the presumed mutation in this gene was not delineated. Thus, Hayashi et al. (1995) concluded that merosin-negative congenital muscular dystrophy does occur in Japan at a low frequency. </p><p>Shorer et al. (1995) demonstrated reduced motor nerve conduction velocities in 10 patients with merosin-negative congenital muscular dystrophy, but no reduction in nerve conduction velocity in 15 merosin-positive congenital muscular dystrophy cases. </p><p>Several forms of congenital muscular dystrophy, namely, FCMD, muscle-eye-brain disease (253280), and Walker-Warburg syndrome (236670), have structural brain abnormalities and associated severe mental retardation. Philpot et al. (1999) demonstrated that a range of structural malformations can also be found in a substantial number of children with merosin-deficient CMD. They reported MRI studies of 14 children with merosin-deficient CMD. All 14 cases had white matter changes, which appeared after the first 6 months of life and persisted with time. The changes were diffuse and the oldest child scanned (14 years) also showed involvement of the U fibers. One child with moderate mental retardation and epilepsy, characterized mainly by complex partial seizures with atypical absences, which had been difficult to treat. MRI showed marked occipital agyria and pontocerebellar hypoplasia. The gyral pattern of the rest of the brain looked normal. Four other cases, all with normal intelligence, also had cerebellar hypoplasia with variable involvement of the pons. </p><p>Taratuto et al. (1999) reported clinical, biopsy, and autopsy findings in a merosin-deficient congenital muscular dystrophy infant with abnormal cortical gyration. The brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. </p><p>Pegoraro et al. (2000) reported a patient with a severe form of CMD caused by compound heterozygous mutations in the LAMA2 gene (156225.0011 and 156225.0012). She presented at birth with severe hypotonia and joint contractures. Motor milestones were severely delayed. She also had central nervous system involvement, including seizures, moderate mental retardation, ventricular dilatation, white matter abnormalities, and pachygyria. Muscle biopsy showed partial LAMA2 immunostaining, which was determined to be an alternatively spliced isoform lacking most of exon 31. </p><p>Jones et al. (2001) reported a series of 5 patients with LAMA2 deficiency and reviewed published reports to characterize its phenotype. Only 1 of the 5 patients reported had a severe classic congenital muscular dystrophy phenotype. Jones et al. (2001) noted that of previously published cases, 12% had a later onset, slowly progressive muscle weakness more accurately designated 'limb-girdle muscular dystrophy.' Mental retardation was found in 6%, seizures in 8%, subclinical cardiac involvement in 3 to 35%, and neuronal migration defects in 4%. At least 25% of the reported cases had achieved independent ambulation. Three patients with LAMA2 deficiency were asymptomatic; 10 had normal MRI, 4 of whom had mutations in the LAMA2 gene. Between 10% and 20% of cases had maximum recorded creatine kinase of less than 1000 units per liter. LAMA2 gene mutations had been identified in 25% of cases, and 68% of these had the classic congenital muscular dystrophy phenotype. Jones et al. (2001) concluded that all dystrophic muscle biopsies, regardless of clinical phenotype, should be studied with antibodies to LAMA2. </p><p>Xiong et al. (2015) reported the clinical features and genetic analysis of 43 children or teens, mostly of Han Chinese descent, with congenital muscular dystrophy and LAMA2 deficiency apparent on skeletal muscle biopsy. Most (29 patients) had hypotonia and weak cry apparent at birth, whereas the remaining patients showed these symptoms and delayed motor development within the first 6 months of life. Thirty-eight patients never achieved independent ambulation, and 5 had mild muscle weakness with impaired gait. Ophthalmoplegia was identified in 23 patients. Brain imaging of all patients showed abnormal T2 intensities in the bilateral periventricular white matter with sparing of the corpus callosum, internal capsule, cerebellum, and brainstem. Eight patients with mental retardation and/or epilepsy had more diffuse white matter abnormalities. Cortical malformations were not observed. Genetic analysis identified biallelic mutations or deletions in the LAMA2 gene; there were no apparent genotype/phenotype correlations. </p>
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<strong>Diagnosis</strong>
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<p><strong><em>Prenatal Diagnosis</em></strong></p><p>
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Naom et al. (1997) concluded that immunocytochemical analysis of the laminin alpha-2 chain in the trophoblast can detect abnormalities in affected fetuses and give normal results in unaffected and carrier fetuses. Nonetheless, they recommended that linkage analysis of the LAMA2 locus also be studied in all cases for the prenatal diagnosis of merosin-deficient congenital muscular dystrophy. </p>
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<strong>Inheritance</strong>
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<p>Using tightly linked informative polymorphic microsatellite markers, D'Alessandro et al. (1999) investigated the pattern of inheritance of the haplotypes associated with the mutant allele in 29 informative merosin-deficient families. This allowed them to identify heterozygous individuals from normal homozygotes, who are clinically, pathologically, and biochemically indistinguishable. By linkage analysis, they found a statistically significant increase in the number of heterozygous individuals carrying either the paternal or the maternal haplotypes associated with the mutant allele. They raised the question of whether there is selection in favor of heterozygotes in this disorder. </p>
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<strong>Mapping</strong>
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<p>Hillaire et al. (1994) demonstrated by homozygosity mapping that merosin-negative congenital muscular dystrophy is linked to a 16-cM region of 6q2 where the laminin M gene maps. In 3 consanguineous, merosin-positive congenital muscular dystrophy families, they found no linkage to 6q2 or to 9q31-q33 where the FCMD locus maps. </p>
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<strong>Molecular Genetics</strong>
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<p>In affected members of 2 families with congenital merosin-deficient muscular dystrophy, Helbling-Leclerc et al. (1995) identified 2 different homozygous mutations (156225.0001-156225.0002) in the LAMA2 gene. They suggested that 'the extracellular location of laminin-2 may allow new therapeutic strategies to restore its presence at the periphery of the muscle fibres and to modify the severe course of this very disabling disease.' </p><p>Complete LAMA2 deficiency causes approximately half of CMD cases. Tezak et al. (2003) noted that many loss-of-function mutations had been reported in these severe, neonatal-onset patients, but only missense mutations had been found in milder CMD with partial LAMA2 deficiency. They studied 9 patients with CMD who showed abnormal white matter signal on brain MRI and partial deficiency of LAMA2 on immunofluorescence of muscle biopsy, and identified changes in the LAMA2 sequence in 6. Five of the 6 changes were novel; these included 3 missense changes (see, e.g., 156225.0009-156225.0010) and 2 splice site mutations. The finding of partial LAMA2 deficiency by immunostaining was not specific for carriers of a LAMA2 gene mutation, as only 2 patients showed clear causative mutations, and an additional 3 showed possible mutations. The clinical presentation and disease progression were the same in LAMA2 mutation-positive and mutation-negative CMD patients. </p><p>Di Blasi et al. (2005) identified 10 LAMA2 mutations, including 9 novel mutations, in 10 of 15 patients with congenital muscular dystrophy and undetectable or greatly reduced muscle expression of LAMA2 protein. All mutation-positive patients had generalized hypotonia and severe weakness from birth, and all had abnormal MRI changes. One founder mutation (156225.0013) was identified and determined to originate from Albania. Two of the 5 patients without detectable LAMA2 mutations and who also did not have white matter changes were found to have mutations in the FKRP gene (606596). </p><p>Oliveira et al. (2008) identified 18 different mutations in the LAMA2 gene, including 14 novel mutations, in 50 (96%) of 52 disease alleles in all 26 patients with a clinical presentation suggestive of MDC1A. Only heterozygous mutations were identified in 2 patients. Ten (31%) patients carried a common 5-kb deletion encompassing exon 56 of the LAMA2 gene (156225.0015). </p>
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<p>In a comprehensive mutation update on LAMA2 mutations, Oliveira et al. (2018) stated that the most frequently reported genotypes are variants that create premature termination codons (PTC) in both disease alleles, are associated with complete deficiency of laminin in muscle biopsy, and cause a severe, congenital muscular dystrophy (MDC1A). In contrast, missense variants, which are present in a smaller number of cases, usually correlate with partial laminin deficiency in muscle biopsy, and cause a milder, later-onset disorder (LGMDR23). </p>
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<p>Taniguchi et al. (2006) performed histologic examination and cDNA microarray analysis of skeletal muscle biopsy specimens from 4 patients with FCMD and 1 with MDC1A at various ages during childhood. Histologic examination showed dystrophic features, fiber size variation, prominent interstitial tissue, and adipose tissue proliferation. Inflammation, necrosis, and regeneration of muscle fibers were less apparent, especially compared to biopsies from patients with Duchenne muscular dystrophy (DMD; 310200). FCMD and MDC1A samples showed increased expression of extracellular matrix genes, such as COL3A1 (120180), THBS4 (600715), and OSF2 (POSTN; 608777), whereas there was downregulation of genes encoding mature muscle components, including MYH7 (160760), TCAP (604488), DES (125660), and MYH1 (160730). Upregulation of gene expression occurred predominantly in muscle fibers and only slightly in fibroblasts. In contrast, a previous microarray analysis of DMD muscle (Noguchi et al., 2003) reported upregulation of genes encoding muscle components, reflecting enhanced active muscle fiber regeneration following degeneration in DMD. Taniguchi et al. (2006) suggested that the primary pathologic feature of FCMD and MDC1A is interstitial fibrosis without muscle degeneration and regeneration, which distinguishes these disorders from DMD. </p><p>Bax (600040)-mediated muscle cell death is a significant contributor to the severe neuromuscular pathology seen in the Lama2-null mouse model of MDC1A. Vishnudas and Miller (2009) analyzed molecular mechanisms of Bax regulation in normal and LAMA2-deficient muscles and cells, including myogenic cells from MDC1A patients. In mouse myogenic cells, Bax coimmunoprecipitated with the multifunctional protein Ku70 (XRCC6; 152690). In addition, cell-permeable pentapeptides designed from Ku70, termed Bax-inhibiting peptides (BIPs), inhibited staurosporine-induced Bax translocation and cell death in mouse myogenic cells. Acetylation of Ku70, which can inhibit binding to Bax and can be an indicator of increased susceptibility to cell death, was more abundant in Lama2-null mouse muscles than in normal mouse muscles. Myotubes formed in culture from human LAMA2-deficient patient myoblasts produced high levels of activated caspase-3 (CASP3; 600636) when grown on poly-L-lysine, but not when grown on a LAMA2-containing substrate or when treated with BIPs. Cytoplasmic Ku70 in human LAMA2-deficient myotubes was both reduced in amount and more highly acetylated than in normal myotubes. Vishnudas and Miller (2009) concluded that increased susceptibility to cell death appears to be an intrinsic property of human LAMA2-deficient myotubes and that Ku70 is a regulator of Bax-mediated pathogenesis. </p>
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<p>The classic mouse muscular dystrophy strain, dy, was described by Michelson et al. (1955). A large literature on the morphologic and biochemical characteristics of the mutation accumulated thereafter. The homozygous mice showed severe progressive muscular dystrophy. In addition, these mice were smaller than their littermates and died between 2 and 6 months of unknown cause. </p><p>Xu et al. (1994) found that the heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting in dy/dy mice, but was expressed normally in heterozygous and wildtype nondystrophic mice. Immunofluorescence confirmed the presence of other major basement membrane proteins in the dystrophic mice. Very low levels of M-laminin heavy chain mRNA were detected by Northern blotting of muscle and heart tissue from dy/dy mice, suggesting that M-laminin heavy chain mRNA may be produced at very low levels or is unstable. Since the gene for the M-laminin heavy chain maps to mouse chromosome 10 in the same region as does the dy locus, Xu et al. (1994) suggested that mutation in that gene causes the muscular dystrophy. Preliminary studies using Southern blotting showed that the M-chain gene was not deleted in the dystrophic mice. </p><p>Sunada et al. (1994) demonstrated that merosin is a native ligand for alpha-dystroglycan, an extracellular component of the dystrophin-glycoprotein complex, and that the gene encoding it in the mouse, Lamm, maps to the same region of chromosome 10 in which the dy locus had been mapped. Analysis of merosin expression in dy mice demonstrated a specific deficiency in skeletal muscle, cardiac muscle, and peripheral nerve. The dysmyelination in the dorsal and ventral nerve roots probably relates to the normal expression of merosin in Schwann cells as well as in muscle basement membrane. </p><p>Xu et al. (1994) identified the molecular basis of a dy allele, called dy(2J), by detecting a mutation in the laminin alpha-2 chain gene. The G-to-A mutation in a splice site consensus sequence caused abnormal splicing and expression of multiple mRNAs. One mRNA was translated into an alpha-2 polypeptide with a deletion in domain VI. The truncated protein apparently lacked important qualities of the wildtype protein and was unable to provide sufficient muscle stability. Xu et al. (1994) stated the following: 'It is becoming increasingly clear that muscular dystrophy may be caused by mutations in a number of proteins involved in stabilizing the muscle cell membrane, including attachment of the muscle cell to the extracellular matrix. In this respect, parallels may be found in the mutations causing skin blistering diseases, epidermolysis bullosa.' </p><p>Kuang et al. (1998) studied mouse models of merosin-deficient congenital muscular dystrophy (MCMD), both spontaneous mutant mice and null mutant mice created by homologous recombination in embryonic stem cells. In mice with complete or partial deficiency of merosin, they expressed a human LAMA2 transgene under the regulation of a muscle-specific creatine kinase promoter. The transgene restored the synthesis and localization of merosin in skeletal muscle, and greatly improved muscle morphology and integrity and the health and longevity of the mice. However, the transgenic mice shared with the nontransgenic dystrophic mice a progressive lameness of hind legs, suggestive of a nerve defect. These results indicated that the absence of merosin in tissues other than muscle, such as nervous tissue, is a critical component of MCMD. Future gene therapy of human MCMD, and perhaps of other forms of muscular dystrophy, may require restoration of a defective gene product in multiple tissues. The observation had previously been made that a characteristic of human MCMD and merosin-deficient muscular dystrophy in mice is that motor nerves are fully myelinated, suggesting that merosin may be important in nervous tissue in addition to muscle. </p><p>Aiming to restore muscle function to a mouse model of LAMA2 deficiency, Moll et al. (2001) designed a minigene of agrin (103320), a protein known for its role in the formation of the neuromuscular junction. Moll et al. (2001) demonstrated that this mini-agrin, which binds to basement membrane and to alpha-dystroglycan (128239), a member of the dystrophin-glycoprotein complex, amends muscle pathology by a mechanism that includes agrin-mediated stabilization of alpha-dystroglycan and the laminin alpha-5 chain (601033). Moll et al. (2001) concluded that their data provided in vivo evidence that a nonhomologous protein in combination with rational protein design can be used to devise therapeutic tools that may restore muscle function in human muscular dystrophies. </p><p>In a review, Shelton and Engvall (2005) stated that animal models of LAMA2 deficiency had been described in the Brittany-Springer spaniel mixed breed dog, and in several cat breeds, including Siamese, Maine Coon cat, and a domestic shorthair mixed breed. The authors noted that the findings of laminin-alpha-2 deficiency in mixed breeds suggests that mutations are present in the gene pools of several breeds of dogs and cats. </p><p>Girgenrath et al. (2009) found that treatment of Lama2-null mice with either minocycline or doxycycline, which inhibit apoptosis, showed clinical and pathologic improvement. Treated mice had increased life span, improved growth, and delayed onset of hindlimb paralysis. Muscles derived from the treated mice were larger than untreated mice, showed decreased inflammation, increased Akt (164730) phosphorylation, and decreased markers of apoptosis, such as Bax (600040) and caspase-3 (CASP3; 600636). The findings indicated that increased apoptosis is a major pathogenic mechanism in LAMA2 deficiency. </p><p>Transgenic overexpression of Lama1 (150320) had been shown to ameliorate muscle wasting and paralysis in mouse models of MDC1A (Gawlik et al., 2004). However, the large size of Lama1 exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy. Kemaladewi et al. (2019) modulated expression of Lama1 in the dy(2j)/dy(2j) mouse model of MDC1a using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators, and single-guide RNAs that target the Lama1 promoter. When presymptomatic mice were treated, Lama1 was upregulated in skeletal muscles and peripheral nerves, which prevented muscle fibrosis and paralysis. Although it had been hypothesized that fibrotic changes in skeletal muscle are irreversible, Kemaladewi et al. (2019) showed that dystrophic features and disease progression were improved and reversed when the treatment was initiated in symptomatic dy(2j)/dy(2j) mice with hindlimb paralysis and muscle fibrosis. Kemaladewi et al. (2019) concluded that their data demonstrated the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which opened the possibility of mutation-independent treatment for patients with MDC1A. </p>
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Vishnudas, V. K., Miller, J. B.
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<strong>Ku70 regulates Bax-mediated pathogenesis in laminin-alpha-2-deficient human muscle cells and mouse models of congenital muscular dystrophy.</strong>
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Xiong, H., Tan, D., Wang, S., Song, S., Yang, H., Gao, K., Liu, A., Jiao, H., Mao, B., Ding, J., Chang, X., Wang, J., Wu, Y., Yuan, Y., Jiang, Y., Zhang, F., Wu, H., Wu, X.
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<strong>Genotype/phenotype analysis in Chinese laminin-alpha-2 deficient congenital muscular dystrophy patients.</strong>
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Xu, H., Christmas, P., Wu, X.-R., Wewer, U. M., Engvall, E.
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<strong>Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.</strong>
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Xu, H., Wu, X.-R., Wewer, U. M., Engvall, E.
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<strong>Murine muscular dystrophy caused by a mutation in the laminin alpha-2 (Lama2) gene.</strong>
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Ada Hamosh - updated : 01/06/2020<br>Cassandra L. Kniffin - updated : 10/04/2018<br>Cassandra L. Kniffin - updated : 3/25/2015<br>George E. Tiller - updated : 10/28/2010<br>Cassandra L. Kniffin - updated : 1/5/2010<br>Cassandra L. Kniffin - updated : 2/23/2009<br>Cassandra L. Kniffin - updated : 10/9/2006<br>Cassandra L. Kniffin - updated : 7/12/2006<br>Cassandra L. Kniffin - updated : 6/5/2006<br>Cassandra L. Kniffin - updated : 1/11/2006
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