5298 lines
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Entry
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- *156225 - LAMININ, ALPHA-2; LAMA2
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*156225</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<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="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/156225">Table View</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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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000196569;t=ENST00000421865" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=3908" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=156225" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000196569;t=ENST00000421865" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000426,NM_001079823" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000426" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=156225" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=01125&isoform_id=01125_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/LAMA2" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/187521,438056,1661108,55961190,62087424,119568465,119568466,119568467,215274259,1134667084,1134667115,1134667117,1677500969,1788519520,2510670048" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P24043" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=3908" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000196569;t=ENST00000421865" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=LAMA2" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=LAMA2" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+3908" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/LAMA2" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:3908" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3908" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr6&hgg_gene=ENST00000421865.3&hgg_start=128883138&hgg_end=129516566&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:6482" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6482" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/lama2" 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=156225[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=156225[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/LAMA2/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000196569" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=LAMA2" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=LAMA2" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LAMA2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/LAMA2" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=LAMA2&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA30271" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:6482" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0261563.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:99912" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/LAMA2#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:99912" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3908/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002459/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3908" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00002248;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060119-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:156225" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3908" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=LAMA2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 111503008, 787037000<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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156225
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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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LAMININ, ALPHA-2; LAMA2
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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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LAMININ 2, HEAVY CHAIN
|
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</span>
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</h4>
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</div>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
|
Other entities represented in this entry:
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</span>
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</p>
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</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
MEROSIN, INCLUDED
|
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</span>
|
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</div>
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<div>
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<span class="h4 mim-font">
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LAMININ 2, INCLUDED<br />
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LAMININ M, INCLUDED; LAMM, INCLUDED
|
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</span>
|
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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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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=LAMA2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LAMA2</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/6/842?start=-3&limit=10&highlight=842">6q22.33</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:128883138-129516566&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">6:128,883,138-129,516,566</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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Muscular dystrophy, congenital, merosin deficient or partially deficient
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Muscular dystrophy, limb-girdle, autosomal recessive 23
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>The LAMA2 gene encodes the alpha-2 laminin subunit of the heterotrimeric extracellular protein laminin-211, also referred to as laminin-2 or merosin. The other subunits include beta-1 (LAMB1; <a href="/entry/150240">150240</a>), and gamma-1, formerly called beta-2 (LAMC1; <a href="/entry/150290">150290</a>). Laminin-211 binds to the glycosylated residues of alpha-dystroglycan (DAG1; <a href="/entry/128239">128239</a>) in skeletal muscle fibers. Laminin-211 is also expressed in a variety of other tissues, most importantly in Schwann cells in peripheral nerves and in the brain (summary by <a href="#15" 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>). <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>Merosin is a protein specifically found in the basement membranes of striated muscle and Schwann cells. It is also found in the basement membrane of placental trophoblasts. <a href="#7" class="mim-tip-reference" title="Ehrig, K., Leivo, I., Argraves, W. S., Ruoslahti, E., Engvall, E. <strong>Merosin, a tissue-specific basement membrane protein, is a laminin-like protein.</strong> Proc. Nat. Acad. Sci. 87: 3264-3268, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2185464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2185464</a>] [<a href="https://doi.org/10.1073/pnas.87.9.3264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2185464">Ehrig et al. (1990)</a> compared merosin with laminin, which is thought to be present in all basement membranes. They found that a cDNA clone derived from a merosin fragment contained a 3.4-kb open reading frame encoding 1,130 amino acids. The deduced amino acid sequence of the merosin polypeptide is similar to that of the C-terminal region of the laminin alpha-1 chain. The sequence identity between merosin and laminin is nearly 40% in this region. Like laminin, merosin is associated with the light chains laminin B1 and laminin B2, and the whole molecule has a cross-like structure similar to that of laminin. The authors estimated that the LAMA2 chain is at least 380 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2185464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Vuolteenaho, R., Nissinen, M., Sainio, K., Byers, M., Eddy, R., Hirvonen, H., Shows, T. B., Sariola, H., Engvall, E., Tryggvason, K. <strong>Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues.</strong> J. Cell Biol. 124: 381-394, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8294519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8294519</a>] [<a href="https://doi.org/10.1083/jcb.124.3.381" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8294519">Vuolteenaho et al. (1994)</a> determined the primary structure of the laminin M chain (symbolized LAMM by them) from cDNA clones isolated from human placental libraries. The complete chain contains a 22-residue signal peptide and 3,088 residues of the mature M chain (3110 residues total). The M chain has a domain structure similar to that of the human and mouse A chains. Northern blot analysis of human fetal tissues showed that the M chain was expressed in most tissues, but not in liver, thymus, or bone. In situ hybridization localized the expression of the M chain gene to cells of mesenchymal origin. In contrast, expression of the A chain was observed only in kidney, testis, neuroretina, and some regions of the brain, as determined by Northern analyses. Epithelial and endothelial cells were negative for both M and A chain gene transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8294519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="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> identified a novel alternatively spliced isoform of LAMA2. Direct sequencing showed that the isoform has a 138-bp in-frame deletion from nucleotides 4629 to 4766 of the coding sequence corresponding to about 70% of exon 31. This splicing event removes 46 amino acids in the cysteine-rich domain IIIa, just proximal to the triple coiled-coil region that associates with the beta-1 and gamma-1 chains of laminin. Immunofluorescent studies suggested that this isoform may impair proper laminin chain assembly. <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>The LAMA2 protein undergoes posttranslational processing and is cleaved at residue 2580 to yield an N-terminal 300-kD peptide and a C-terminal 80-kD peptide, which are subsequently connected through a noncovalent process (summary by <a href="#15" 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>). <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="#2" class="mim-tip-reference" title="Arahata, K., Hayashi, Y. K., Mizuno, Y., Yoshida, M., Ozawa, E. <strong>Dystrophin-associated glycoprotein and dystrophin co-localisation at sarcolemma in Fukuyama congenital muscular dystrophy. (Letter)</strong> Lancet 342: 623-624, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8102757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8102757</a>] [<a href="https://doi.org/10.1016/0140-6736(93)91454-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8102757">Arahata et al. (1993)</a> indicated that merosin is the same as laminin M, a striated muscle-specific, basal-lamina-associated protein. They found that the protein was reduced in the muscle fibers in Fukuyama congenital muscular dystrophy (<a href="/entry/253800">253800</a>), suggesting that it may play a primary role in the pathogenesis of that disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8102757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The laminin alpha-2 subunit is expressed in Schwann cells. <a href="#14" class="mim-tip-reference" title="Ng, V., Zanazzi, G., Timpl, R., Talts, J. F., Salzer, J. L., Brennan, P. J., Rambukkana, A. <strong>Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae.</strong> Cell 103: 511-524, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11081637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11081637</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)00142-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11081637">Ng et al. (2000)</a> provided evidence for the involvement of the specific trisaccharide unit of the phenolic glycolipid-1 (PGL1) of Mycobacterium leprae (see <a href="/entry/246300">246300</a>) in determining the bacterial predilection to the peripheral nerve. PGL1 binds specifically to the native laminin-2 in the basal lamina of Schwann cell-axon units. This binding is mediated by the LG1, LG4, and LG5 modules present in the naturally cleaved fragments of the peripheral nerve LAMA2 chain, and is inhibited by the synthetic terminal trisaccharide of PGL1. PGL1 is involved in the M. leprae invasion of Schwann cells through the basal lamina in a laminin-2-dependent pathway. The results indicated a novel role of a bacterial glycolipid in determining the nerve predilection of a human pathogen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11081637" 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="#21" class="mim-tip-reference" title="Zhang, X., Vuolteenaho, R., Tryggvason, K. <strong>Structure of the human laminin alpha-2-chain gene (LAMA2), which is affected in congenital muscular dystrophy.</strong> J. Biol. Chem. 271: 27664-27669, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8910357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8910357</a>] [<a href="https://doi.org/10.1074/jbc.271.44.27664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8910357">Zhang et al. (1996)</a> determined the genomic structure of the human LAMA2 gene. The gene spans over 260 kb and contains 64 exons. Two of the exons are unusually small, being 6 and 12 bp, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8910357" 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="#20" class="mim-tip-reference" title="Vuolteenaho, R., Nissinen, M., Sainio, K., Byers, M., Eddy, R., Hirvonen, H., Shows, T. B., Sariola, H., Engvall, E., Tryggvason, K. <strong>Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues.</strong> J. Cell Biol. 124: 381-394, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8294519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8294519</a>] [<a href="https://doi.org/10.1083/jcb.124.3.381" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8294519">Vuolteenaho et al. (1994)</a> localized the human LAMA2 gene to 6q22-q23 by a combination of somatic cell hybrid analysis and in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8294519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By FISH, <a href="#18" class="mim-tip-reference" title="Sallinen, R., Kuang, W., Engvall, E., Palotie, A., Wessman, M., Horelli-Kuitunen, N. <strong>Assignment of laminin alpha 2-chain gene (Lama2) to mouse chromosome 10A4-B1 by fluorescence in situ hybridization.</strong> Cytogenet. Cell Genet. 87: 195-196, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10702665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10702665</a>] [<a href="https://doi.org/10.1159/000015464" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10702665">Sallinen et al. (1999)</a> mapped the mouse Lama2 gene to chromosome 10A4-B1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10702665" 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><strong><em>Muscular Dystrophy, Congenital Merosin-Deficient, Type 1A</em></strong></p><p>
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In affected members of 2 families with congenital merosin-deficient muscular dystrophy type 1A (MDC1A; <a href="/entry/607855">607855</a>), <a href="#12" 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="#0001">156225.0001</a>-<a href="#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="#19" 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. Except for one, each of the gene changes identified was novel, including 3 missense changes (see, e.g., <a href="#0009">156225.0009</a>-<a href="#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 the 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="#5" 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 the mutation-positive patients had generalized hypotonia and severe weakness from birth, and all had abnormal MRI changes. One founder mutation (<a href="#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="#16" 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 from 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="#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><p><strong><em>Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 23</em></strong></p><p>
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In 5 patients from 4 families with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; <a href="/entry/618138">618138</a>), <a href="#8" class="mim-tip-reference" title="Gavassini, B. F., Carboni, N., Nielsen, J. E., Danielsen, E. R, Thomsen, C., Svenstrup, K., Bello, L. Maioli, M. A., Marrosu, G., Ticca, A. F., Mura, M., Marrosu, M. G., Soraru, G., Angelini, C., Vissing, J., Pegoraro, E. <strong>Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations.</strong> Muscle Nerve 44: 703-709, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21953594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21953594</a>] [<a href="https://doi.org/10.1002/mus.22132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21953594">Gavassini et al. (2011)</a> identified homozygous or compound heterozygous mutations in the LAMA2 gene (see, e.g., <a href="#0016">156225.0016</a> and <a href="#0017">156225.0017</a>). There were 4 missense mutations, 1 splice site mutation, and 1 in-frame deletion. The mutations were located in both the globular and the rod-like domains of the protein. Functional studies of the variants were not performed, but the splice site mutation was confirmed to result in a frameshift in patient cells. Muscle biopsy showed partial LAMA2 deficiency in all patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21953594" 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 girl with LGMDR23, <a href="#3" class="mim-tip-reference" title="Chan, S. H. S., Foley, R., Phadke, R., Mathew, A. A., Pitt, M., Sewry, C., Muntoni, F. <strong>Limb girdle muscular dystrophy due to LAMA2 mutations: diagnostic difficulties due to associated peripheral neuropathy.</strong> Neuromusc. Disord. 24: 677-683, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24957499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24957499</a>] [<a href="https://doi.org/10.1016/j.nmd.2014.05.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24957499">Chan et al. (2014)</a> identified compound heterozygous mutations in the LAMA2 gene (Q131X, <a href="#0018">156225.0018</a> and A1496V, <a href="#0019">156225.0019</a>). The mutations segregated with the disorder in the family. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24957499" 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="#15" 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="#9" 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> generated mice expressing a Lama1 transgene in skeletal muscle of Lama2-deficient mice. Lama1 is not normally expressed in muscle, but transgenic Lama1 was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains (LAMA4, <a href="/entry/600133">600133</a>; LAMB2, <a href="/entry/150325">150325</a>). In 4-month-old mice, Lama1 could fully prevent development of muscular dystrophy in several muscles, and partially in others. <a href="#9" 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> concluded that the Lama1 transgene not only reversed the appearance of histopathologic features of the disease to a remarkable degree, but also greatly improved health and longevity of the mice. <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'})"><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="#6" class="mim-tip-reference" title="Dominov, J. A., Kravetz, A. J., Ardelt, M., Kostek, C. A., Beermann, M. L., Miller, J. B. <strong>Muscle-specific BCL2 expression ameliorates muscle disease in laminin alpha-2-deficient, but not in dystrophin-deficient, mice.</strong> Hum. Molec. Genet. 14: 1029-1040, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15757977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15757977</a>] [<a href="https://doi.org/10.1093/hmg/ddi095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15757977">Dominov et al. (2005)</a> generated mdx (<a href="/entry/300377">300377</a>) or Lama2-null mice that also overexpressed muscle-specific human BCL2 (<a href="/entry/151430">151430</a>). In mdx mice, overexpression of BCL2 failed to produce any significant differences in muscle pathology; however, in Lama2-null mice, muscle-specific overexpression of BCL2 led to a several-fold increase in life span and an increased growth rate. <a href="#6" class="mim-tip-reference" title="Dominov, J. A., Kravetz, A. J., Ardelt, M., Kostek, C. A., Beermann, M. L., Miller, J. B. <strong>Muscle-specific BCL2 expression ameliorates muscle disease in laminin alpha-2-deficient, but not in dystrophin-deficient, mice.</strong> Hum. Molec. Genet. 14: 1029-1040, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15757977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15757977</a>] [<a href="https://doi.org/10.1093/hmg/ddi095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15757977">Dominov et al. (2005)</a> concluded that BCL2-mediated apoptosis appeared to play a significant role in pathogenesis of congenital muscular dystrophy type 1A due to LAMA2 deficiency but not in Duchenne muscular dystrophy (DMD; <a href="/entry/310200">310200</a>) due to dystrophin deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15757977" 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 mice, <a href="#13" class="mim-tip-reference" title="Millay, D. P., Sargent, M. A., Osinska, H., Baines, C. P., Barton, E. R., Vuagniaux, G., Sweeney, H. L., Robbins, J., Molkentin, J. D. <strong>Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy.</strong> Nature Med. 14: 442-447, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18345011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18345011</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18345011[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm1736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18345011">Millay et al. (2008)</a> showed the deletion of the gene encoding cyclophilin D, Ppif (<a href="/entry/604486">604486</a>), rendered mitochondria largely insensitive to the calcium overload-induced swelling associated with a defective sarcolemma, thus reducing myofiber necrosis in 2 distinct models of muscular dystrophy. Mice lacking delta-sarcoglycan (Scgd-null mice; see <a href="/entry/601411">601411</a>) showed markedly less dystrophic disease in both skeletal muscle and heart in the absence of Ppif. Moreover, the premature lethality associated with deletion of Lama2 was rescued, as were other indices of dystrophic disease. Treatment with the cyclophilin inhibitor Debio-025 similarly reduced mitochondrial swelling and necrotic disease manifestations in mdx mice, a model of Duchenne muscular dystrophy, and in Scgd-null mice. Thus, mitochondrial-dependent necrosis represents a prominent disease mechanism in muscular dystrophy, suggesting that inhibition of cyclophilin D could provide a new pharmacologic treatment strategy for these diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18345011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>19 Selected Examples</a>):</strong>
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<a href="/allelicVariants/156225" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=156225[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554278541 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554278541;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1554278541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1554278541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000671265" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000671265" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000671265</a>
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<p>In a family with merosin-deficient congenital muscular dystrophy (<a href="/entry/607855">607855</a>), <a href="#12" 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> found a 193-bp deletion corresponding to all of exon 31 of the gene. From the sequence of flanking introns, they found an A-to-T transversion at the -2 position of the consensus acceptor splice site of exon 31. Two affected CMD children were homozygous, while their parents and sibs were heterozygous. The mutation occurred 2 nucleotides to the 5-prime side of NT4573. <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>
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<strong>.0002 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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LAMA2, GLN1241TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913569 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913569;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015360 OR RCV000790720 OR RCV000818341 OR RCV003225924" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015360, RCV000790720, RCV000818341, RCV003225924" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015360...</a>
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<p>In affected members of a nonconsanguineous family with congenital merosin-deficient muscular dystrophy (<a href="/entry/607855">607855</a>), <a href="#12" 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> found by SSCP analysis aberrant conformers for exon 24 of the LAMA2 gene. Sequencing of exon 24 revealed a homozygous C-to-T substitution at position 3767 of their cDNA. The mutation caused a change in a CAA codon for glutamine to a TAA stop codon (Q1241X) in domain IVa. <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>
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<strong>.0003 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
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LAMA2, IVS25, T-C, +2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554269966 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554269966;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1554269966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1554269966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015363 OR RCV000518321 OR RCV000853232 OR RCV000985057 OR RCV001857909 OR RCV004527387" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015363, RCV000518321, RCV000853232, RCV000985057, RCV001857909, RCV004527387" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015363...</a>
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<p>In 2 sibs with mild congenital merosin-deficient muscular dystrophy (<a href="/entry/607855">607855</a>) in a consanguineous Saudi Arabian family, <a href="#1" class="mim-tip-reference" title="Allamand, V., Sunada, Y., Salih, M. A. M., Straub, V., Ozo, C. O., Al-Turaiki, M. H. S., Akbar, M., Kolo, T., Colognato, H., Zhang, X., Sorokin, L. M., Yurchenco, P. D., Tryggvason, K., Campbell, K. P. <strong>Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha-2-chain.</strong> Hum. Molec. Genet. 6: 747-752, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158149</a>] [<a href="https://doi.org/10.1093/hmg/6.5.747" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9158149">Allamand et al. (1997)</a> found that the laminin alpha-2 chain had an internal deletion as the result of a splice site mutation in the LAMA2 gene that caused the splicing out of exon 25. The predicted protein lacked 63 amino acids in domain IVa, which forms a globular structure on the short arm of the alpha-2 chain. Antibodies against the G-domain of the laminin alpha-2 chain showed a near normal expression in skeletal muscle, whereas antibodies against the N-terminal region showed a drastic reduction. These patients appeared mildly affected compared to others who completely lacked this protein. <a href="#1" class="mim-tip-reference" title="Allamand, V., Sunada, Y., Salih, M. A. M., Straub, V., Ozo, C. O., Al-Turaiki, M. H. S., Akbar, M., Kolo, T., Colognato, H., Zhang, X., Sorokin, L. M., Yurchenco, P. D., Tryggvason, K., Campbell, K. P. <strong>Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha-2-chain.</strong> Hum. Molec. Genet. 6: 747-752, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158149</a>] [<a href="https://doi.org/10.1093/hmg/6.5.747" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9158149">Allamand et al. (1997)</a> compared the situation to Becker muscular dystrophy (<a href="/entry/300376">300376</a>), in which in-frame deletions of the dystrophin gene (<a href="/entry/300377">300377</a>) result in the expression of a semifunctional protein and leads to a mild phenotype. The splice site mutation was a T-to-C transition at position +2 of the consensus donor splice site of exon 25. This mutation was found in homozygous state in both patients and induced the splicing out of exon 25 by alternately using the donor splice site of exon 24. Both parents were heterozygous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9158149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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LAMA2, LEU2564PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913570 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913570;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913570?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015364 OR RCV003330391" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015364, RCV003330391" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015364...</a>
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<p>In a patient with congenital merosin-deficient muscular dystrophy (<a href="/entry/607855">607855</a>) characterized by difficulty walking, hypotonia, proximal weakness, hyporeflexia, and white matter hypodensity on MRI, <a href="#11" class="mim-tip-reference" title="He, Y., Jones, K. J., Vignier, N., Morgan, G., Chevallay, M., Barois, A., Estournet-Mathiaud, B., Hori, H., Mizuta, T., Tome, F. M. S., North, K. N., Guicheney, P. <strong>Congenital muscular dystrophy with primary partial laminin alpha-2 chain deficiency: molecular study.</strong> Neurology 57: 1319-1322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591858</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591858">He et al. (2001)</a> identified compound heterozygosity in the LAMA2 gene: a missense mutation resulting in a leu2564-to-pro (L2564P) substitution and a nonsense mutation at codon 3085 (R3085X; <a href="#0005">156225.0005</a>). Laminin alpha-2 antibody labeling was mildly reduced. <a href="#11" class="mim-tip-reference" title="He, Y., Jones, K. J., Vignier, N., Morgan, G., Chevallay, M., Barois, A., Estournet-Mathiaud, B., Hori, H., Mizuta, T., Tome, F. M. S., North, K. N., Guicheney, P. <strong>Congenital muscular dystrophy with primary partial laminin alpha-2 chain deficiency: molecular study.</strong> Neurology 57: 1319-1322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591858</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591858">He et al. (2001)</a> suggested that the patient's mild phenotype correlated with partial deficiency of laminin alpha-2 due to expression of the L2564P allele. The authors noted the importance of using antibodies against different domains of the protein for correct immunohistochemical characterization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913571 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913571;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913571?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the arg3085-to-ter (R3085X) substitution in the LAMA2 gene that was found in compound heterozygous state in a patient with congenital merosin-deficient muscular dystrophy (<a href="/entry/607855">607855</a>) by <a href="#11" class="mim-tip-reference" title="He, Y., Jones, K. J., Vignier, N., Morgan, G., Chevallay, M., Barois, A., Estournet-Mathiaud, B., Hori, H., Mizuta, T., Tome, F. M. S., North, K. N., Guicheney, P. <strong>Congenital muscular dystrophy with primary partial laminin alpha-2 chain deficiency: molecular study.</strong> Neurology 57: 1319-1322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591858</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591858">He et al. (2001)</a>, see <a href="#0004">156225.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591858" 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 patient with congenital merosin-deficient muscular dystrophy (<a href="/entry/607855">607855</a>) characterized by motor delay with inability to walk, hypotonia, scoliosis, contractures, seizures, and white matter hypodensity on MRI, <a href="#11" class="mim-tip-reference" title="He, Y., Jones, K. J., Vignier, N., Morgan, G., Chevallay, M., Barois, A., Estournet-Mathiaud, B., Hori, H., Mizuta, T., Tome, F. M. S., North, K. N., Guicheney, P. <strong>Congenital muscular dystrophy with primary partial laminin alpha-2 chain deficiency: molecular study.</strong> Neurology 57: 1319-1322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591858</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591858">He et al. (2001)</a> identified a homozygous 1-bp deletion (8314delA) in the LAMA2 gene, resulting in a frameshift and premature stop codon. <a href="#11" class="mim-tip-reference" title="He, Y., Jones, K. J., Vignier, N., Morgan, G., Chevallay, M., Barois, A., Estournet-Mathiaud, B., Hori, H., Mizuta, T., Tome, F. M. S., North, K. N., Guicheney, P. <strong>Congenital muscular dystrophy with primary partial laminin alpha-2 chain deficiency: molecular study.</strong> Neurology 57: 1319-1322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591858</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591858">He et al. (2001)</a> suggested that the reduced amount of the truncated protein correlated with the severe phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs202247790 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202247790;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs202247790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs202247790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000031899 OR RCV000078754 OR RCV000200517 OR RCV000230453 OR RCV000557045 OR RCV004813047 OR RCV005031466" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000031899, RCV000078754, RCV000200517, RCV000230453, RCV000557045, RCV004813047, RCV005031466" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000031899...</a>
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<p>In a patient with congenital merosin-deficient muscular dystrophy (<a href="/entry/607855">607855</a>) characterized by inability to walk, kyphoscoliosis, contractures, chest deformity, respiratory insufficiency, and white matter hypodensity on MRI, <a href="#11" class="mim-tip-reference" title="He, Y., Jones, K. J., Vignier, N., Morgan, G., Chevallay, M., Barois, A., Estournet-Mathiaud, B., Hori, H., Mizuta, T., Tome, F. M. S., North, K. N., Guicheney, P. <strong>Congenital muscular dystrophy with primary partial laminin alpha-2 chain deficiency: molecular study.</strong> Neurology 57: 1319-1322, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591858</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591858">He et al. (2001)</a> identified a 2-bp deletion (2098delAG) in the LAMA2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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LAMA2, ARG2578TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913572 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913572;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913572?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015366 OR RCV000763556 OR RCV000790757 OR RCV001068136 OR RCV001794447 OR RCV002288491 OR RCV002513061 OR RCV004532360" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015366, RCV000763556, RCV000790757, RCV001068136, RCV001794447, RCV002288491, RCV002513061, RCV004532360" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015366...</a>
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<p><a href="#4" class="mim-tip-reference" title="Coral-Vazquez, R. M., Rosas-Vargas, H., Meza-Espinosa, P., Mendoza, I., Huicochea, J. C., Ramon, G., Salamanca, F. <strong>Severe congenital muscular dystrophy in a Mexican family with a new nonsense mutation (R2578X) in the laminin alpha-2 gene.</strong> J. Hum. Genet. 48: 91-95, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601554</a>] [<a href="https://doi.org/10.1007/s100380300013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601554">Coral-Vazquez et al. (2003)</a> reported the case of an 8-month-old Mexican female, from a consanguineous family, with classic merosin-deficient congenital muscular dystrophy (<a href="/entry/607855">607855</a>). In addition to elevated serum creatine kinase and dystrophic changes on muscle biopsy, there were abnormalities on brain MRI. Immunofluorescence analysis demonstrated complete absence of LAMA2. In contrast, all components of the dystrophin-glycoprotein complex appeared normal. Mutation analysis of the LAMA2 gene identified a homozygous 7781C-T transition in exon 54 that resulted in an arg2578-to-ter (R2578X) mutation in the G domain of the protein. Both parents and some other relatives were carriers of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913573 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913573;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015367 OR RCV000287266 OR RCV001239611" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015367, RCV000287266, RCV001239611" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015367...</a>
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<p>In a patient with congenital muscular dystrophy and partial LAMA2 deficiency (<a href="/entry/607855">607855</a>), <a href="#19" 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> found compound heterozygosity for a 2633T-C transition in exon 18 of the LAMA2 gene, resulting in a change of a conserved cysteine residue at codon 862 to arg (C862R), and another mutation that caused abnormalities of transcription but was not fully characterized. This patient reached the ability to walk unsupported, in contrast with patients with complete LAMA2 deficiency CMD who never achieve this ability. In her late teens, she began to lose previously acquired cognitive abilities. Although mental retardation had previously been reported in CMDs, dementia was unusual. A possible explanation is ascertainment bias, since most of the CMD patients reported were studied at a young age, while dementia may develop at a later stage of the disease. <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>
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<strong>.0010 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913574 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913574;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913574?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015368 OR RCV000078747 OR RCV000822637" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015368, RCV000078747, RCV000822637" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015368...</a>
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<p>In a patient with congenital muscular dystrophy and partial LAMA2 deficiency (<a href="/entry/607855">607855</a>), <a href="#19" 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> found compound heterozygosity for a 1629G-A transition in exon 10 of the LAMA2 gene, resulting in a change of a conserved cysteine residue at codon 527 to tyr (C527Y), and a second mutation that caused transcription abnormalities but was not fully characterized. <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>
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<strong>.0011 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913575 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913575;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913575?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015369 OR RCV000674731 OR RCV001203616" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015369, RCV000674731, RCV001203616" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015369...</a>
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<p>In a patient with congenital muscular dystrophy and partial LAMA2 deficiency (<a href="/entry/607855">607855</a>), <a href="#17" 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> identified compound heterozygosity for 2 mutations in the LAMA2 gene: a 4694C-T transition in exon 31, resulting in an arg1549-to-ter (R1549X) substitution, and a 7196C-T transition in exon 49, resulting in an arg2383-to-ter (R2383X; <a href="#0012">156225.0012</a>) substitution. The patient had a severe form of the disorder with central nervous system involvement including seizures, mental retardation, ventricular dilatation, and pachygyria. Each parent was heterozygous for 1 of the mutations. <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>
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<strong>.0012 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913576 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913576;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913576?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015370 OR RCV000179066 OR RCV000654712 OR RCV000790693 OR RCV002444431 OR RCV002476971" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015370, RCV000179066, RCV000654712, RCV000790693, RCV002444431, RCV002476971" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015370...</a>
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<p>For discussion of the 7196C-T transition in exon 49 of the LAMA2 gene, resulting in an arg2383-to-ter (R2383X) substitution, that was found in a patient with congenital muscular dystrophy and partial LAMA2 deficiency (<a href="/entry/607855">607855</a>) by <a href="#17" 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>, see <a href="#0011">156225.0011</a>. <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>
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<strong>.0013 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913577 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913577;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913577?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121913577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015371 OR RCV000824626 OR RCV001091209" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015371, RCV000824626, RCV001091209" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015371...</a>
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<p>In 2 unrelated patients with congenital merosin-deficient muscular dystrophy (MDC1A; <a href="/entry/607855">607855</a>), <a href="#5" 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 a 2901C-A transversion in exon 21 of the LAMA2 gene, resulting in a cys967-to-ter (C967X) substitution and truncation of the protein in domain IIIb. One of the patients, who was Italian, was homozygous for the C967X mutation, and the other patient, from Albania, was compound heterozygous for the C967X mutation and a 1-bp deletion (825delC) in exon 6 of the LAMA2 gene, resulting in a frameshift and premature stop codon. The C967X mutation had previously been reported in affected members of 2 Italian families originating from the southern Adriatic coast (<a href="#10" class="mim-tip-reference" title="Guicheney, P., Vignier, N., Zhang, X., He, Y., Cruaud, C., Frey, V., Helbling-Leclerc, A., Richard, P., Estournet, B., Merlini, L., Topaloglu, H., Mora, M., Harpey, J.-P., Haenggeli, C.-A., Barois, A., Hainque, B., Schwartz, K., Tome, F. M. S., Fardeau, M., Tryggvason, K. <strong>PCR based mutation screening of the laminin alpha-2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.</strong> J. Med. Genet. 35: 211-217, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9541105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9541105</a>] [<a href="https://doi.org/10.1136/jmg.35.3.211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9541105">Guicheney et al., 1998</a>). Haplotype analysis suggested a remote founder effect, with the mutation most likely originating in Albania. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16216942+9541105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1562275792 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1562275792;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1562275792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1562275792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 1-bp deletion (825delC) in exon 6 of the LAMA2 gene, resulting in a frameshift and premature stop codon, that was found in compound heterozygous state in 2 unrelated patients with congenital merosin-deficient muscular dystrophy by <a href="#5" 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>, see <a href="#0013">156225.0013</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>
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<strong>.0015 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015373" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015373" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015373</a>
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<p>In 8 patients with MDC1A (<a href="/entry/607855">607855</a>), <a href="#16" 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 a 5-kb deletion encompassing exon 56 of the LAMA2. Two patients were homozygous for the deletion, and 6 were compound heterozygous with another pathogenic LAMA2 mutation. The deletion was detected in 31% of 26 patients with the disorder. Although all patients were of Spanish or Portuguese descent, no common haplotypes were found. <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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1562273395 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1562273395;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1562273395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1562273395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 sibs (patients 2 and 3) with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; <a href="/entry/618138">618138</a>), <a href="#8" class="mim-tip-reference" title="Gavassini, B. F., Carboni, N., Nielsen, J. E., Danielsen, E. R, Thomsen, C., Svenstrup, K., Bello, L. Maioli, M. A., Marrosu, G., Ticca, A. F., Mura, M., Marrosu, M. G., Soraru, G., Angelini, C., Vissing, J., Pegoraro, E. <strong>Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations.</strong> Muscle Nerve 44: 703-709, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21953594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21953594</a>] [<a href="https://doi.org/10.1002/mus.22132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21953594">Gavassini et al. (2011)</a> identified compound heterozygous mutations in the LAMA2 gene: a c.728T-C transition in exon 5, resulting in a leu243-to-pro (L243P) substitution at a highly conserved residue in protein domain VI, and a complex splice site mutation in intron 33 (c.4860+2T-G_4860+3insGCC; <a href="#0017">156225.0017</a>), resulting in a splice site alteration, a frameshift, and premature termination (Phe1573_Lys1620delinsSerfsTer49). The splice site defect was confirmed by analysis of patient cells. Additional functional studies were not performed, but muscle biopsy showed partial LAMA2 deficiency. Expression of LAMA5 (<a href="/entry/601033">601033</a>) was increased. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21953594" 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>For discussion of the complex splice site mutation in intron 33 of the LAMA2 gene (c.4860+2T-G_4860+3insGCC), resulting in a splice site alteration, a frameshift, and premature termination (Phe1573_Lys1620delinsSerfsTer49), that was found in compound heterozygous state in 2 sibs with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; <a href="/entry/618138">618138</a>) by <a href="#8" class="mim-tip-reference" title="Gavassini, B. F., Carboni, N., Nielsen, J. E., Danielsen, E. R, Thomsen, C., Svenstrup, K., Bello, L. Maioli, M. A., Marrosu, G., Ticca, A. F., Mura, M., Marrosu, M. G., Soraru, G., Angelini, C., Vissing, J., Pegoraro, E. <strong>Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations.</strong> Muscle Nerve 44: 703-709, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21953594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21953594</a>] [<a href="https://doi.org/10.1002/mus.22132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21953594">Gavassini et al. (2011)</a>, see <a href="#0016">156225.0016</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21953594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1562200866 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1562200866;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1562200866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1562200866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000709619 OR RCV001861944" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000709619, RCV001861944" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000709619...</a>
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<p>In an 11-year-old girl with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; <a href="/entry/618138">618138</a>), <a href="#3" class="mim-tip-reference" title="Chan, S. H. S., Foley, R., Phadke, R., Mathew, A. A., Pitt, M., Sewry, C., Muntoni, F. <strong>Limb girdle muscular dystrophy due to LAMA2 mutations: diagnostic difficulties due to associated peripheral neuropathy.</strong> Neuromusc. Disord. 24: 677-683, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24957499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24957499</a>] [<a href="https://doi.org/10.1016/j.nmd.2014.05.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24957499">Chan et al. (2014)</a> identified compound heterozygous mutations in the LAMA2 gene: a c.391C-T transition in exon 3, resulting in a gln131-to-ter (Q131X) substitution, and a c.4487C-T transition in exon 31, resulting in an ala1496-to-val (A1496V; <a href="#0019">156225.0019</a>) substitution. The Q131X mutation, which was inherited from the unaffected mother, occurred in domain VI of the protein, whereas the A1496V mutation, which was inherited from the unaffected father, occurred in domain IIIa of the protein. The patient also carried a heterozygous variant of unknown significance in the LAMA2 gene (C199S) that was inherited from the father. Functional studies of the variants were not performed, but skeletal muscle biopsy from the patient showed decreased LAMA2 in muscle fibers and in intramuscular motor nerves. Expression of LAMA5 (<a href="/entry/601033">601033</a>) was increased. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24957499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs147077184 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147077184;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs147077184?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs147077184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs147077184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000194655 OR RCV000509423 OR RCV000659062 OR RCV000709620 OR RCV001081183 OR RCV001152676 OR RCV004537432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000194655, RCV000509423, RCV000659062, RCV000709620, RCV001081183, RCV001152676, RCV004537432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000194655...</a>
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<p>For discussion of the c.4487C-T transition in exon 31 of the LAMA2 gene, resulting in an ala1496-to-val (A1496V) substitution, that was found in compound heterozygous state in a patient with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; <a href="/entry/618138">618138</a>) by <a href="#3" class="mim-tip-reference" title="Chan, S. H. S., Foley, R., Phadke, R., Mathew, A. A., Pitt, M., Sewry, C., Muntoni, F. <strong>Limb girdle muscular dystrophy due to LAMA2 mutations: diagnostic difficulties due to associated peripheral neuropathy.</strong> Neuromusc. Disord. 24: 677-683, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24957499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24957499</a>] [<a href="https://doi.org/10.1016/j.nmd.2014.05.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24957499">Chan et al. (2014)</a>, see <a href="#0018">156225.0018</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24957499" 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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Allamand, V., Sunada, Y., Salih, M. A. M., Straub, V., Ozo, C. O., Al-Turaiki, M. H. S., Akbar, M., Kolo, T., Colognato, H., Zhang, X., Sorokin, L. M., Yurchenco, P. D., Tryggvason, K., Campbell, K. P.
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<strong>Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha-2-chain.</strong>
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Hum. Molec. Genet. 6: 747-752, 1997.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.55.8.1128" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Sallinen1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sallinen, R., Kuang, W., Engvall, E., Palotie, A., Wessman, M., Horelli-Kuitunen, N.
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|
<strong>Assignment of laminin alpha 2-chain gene (Lama2) to mouse chromosome 10A4-B1 by fluorescence in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 87: 195-196, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10702665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10702665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10702665" 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/10.1159/000015464" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Tezak2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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.
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<strong>Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha-2 (LAMA2) deficiency.</strong>
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Hum. Mutat. 21: 103-111, 2003.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.10157" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Vuolteenaho1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vuolteenaho, R., Nissinen, M., Sainio, K., Byers, M., Eddy, R., Hirvonen, H., Shows, T. B., Sariola, H., Engvall, E., Tryggvason, K.
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|
<strong>Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues.</strong>
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J. Cell Biol. 124: 381-394, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8294519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8294519</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8294519" 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/10.1083/jcb.124.3.381" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Zhang1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, X., Vuolteenaho, R., Tryggvason, K.
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<strong>Structure of the human laminin alpha-2-chain gene (LAMA2), which is affected in congenital muscular dystrophy.</strong>
|
|
J. Biol. Chem. 271: 27664-27669, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8910357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8910357</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8910357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.271.44.27664" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/04/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/23/2009<br>Ada Hamosh - updated : 6/11/2008<br>George E. Tiller - updated : 2/7/2008<br>George E. Tiller - updated : 1/16/2007<br>Cassandra L. Kniffin - updated : 10/9/2006<br>Cassandra L. Kniffin - updated : 6/5/2006<br>Victor A. McKusick - updated : 3/7/2003<br>Victor A. McKusick - updated : 3/6/2003<br>Cassandra L. Kniffin - updated : 12/3/2002<br>Michael J. Wright - updated : 7/30/2002<br>Ada Hamosh - updated : 9/21/2001<br>Carol A. Bocchini - updated : 2/15/2001<br>Stylianos E. Antonarakis - updated : 11/21/2000<br>Victor A. McKusick - updated : 1/12/2000<br>Victor A. McKusick - updated : 6/3/1999<br>Victor A. McKusick - updated : 10/8/1998<br>Victor A. McKusick - updated : 9/30/1998<br>Victor A. McKusick - updated : 6/23/1997<br>Victor A. McKusick - updated : 5/19/1997<br>Jennifer P. Macke - updated : 4/24/1997<br>Orest Hurko - edited : 4/13/1996<br>Orest Hurko - updated : 4/4/1996<br>Orest Hurko - updated : 3/9/1996<br>Orest Hurko - updated : 3/6/1996<br>Orest Hurko - updated : 2/5/1996<br>Orest Hurko - updated : 8/15/1995
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 7/23/1991
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/02/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/08/2018<br>carol : 10/05/2018<br>ckniffin : 10/04/2018<br>wwang : 04/02/2009<br>ckniffin : 2/23/2009<br>alopez : 6/13/2008<br>terry : 6/11/2008<br>terry : 6/6/2008<br>wwang : 2/27/2008<br>wwang : 2/14/2008<br>terry : 2/7/2008<br>wwang : 1/24/2007<br>terry : 1/16/2007<br>wwang : 10/18/2006<br>ckniffin : 10/9/2006<br>wwang : 6/23/2006<br>ckniffin : 6/5/2006<br>carol : 6/10/2003<br>ckniffin : 6/6/2003<br>ckniffin : 6/6/2003<br>carol : 3/21/2003<br>tkritzer : 3/12/2003<br>terry : 3/7/2003<br>terry : 3/6/2003<br>cwells : 12/10/2002<br>ckniffin : 12/3/2002<br>tkritzer : 8/6/2002<br>tkritzer : 8/2/2002<br>tkritzer : 8/1/2002<br>terry : 7/30/2002<br>alopez : 3/13/2002<br>alopez : 9/24/2001<br>terry : 9/21/2001<br>mcapotos : 2/16/2001<br>carol : 2/15/2001<br>mgross : 11/21/2000<br>mgross : 4/7/2000<br>mgross : 2/1/2000<br>terry : 1/12/2000<br>carol : 6/15/1999<br>jlewis : 6/15/1999<br>terry : 6/3/1999<br>carol : 10/13/1998<br>terry : 10/8/1998<br>carol : 10/1/1998<br>terry : 9/30/1998<br>terry : 7/24/1998<br>alopez : 7/2/1998<br>dkim : 7/2/1998<br>terry : 6/1/1998<br>mark : 7/3/1997<br>terry : 6/23/1997<br>terry : 6/18/1997<br>alopez : 6/2/1997<br>alopez : 5/21/1997<br>terry : 5/19/1997<br>alopez : 5/13/1997<br>alopez : 5/2/1997<br>alopez : 4/24/1997<br>mark : 4/13/1996<br>mark : 4/4/1996<br>mark : 4/4/1996<br>terry : 3/22/1996<br>mark : 3/9/1996<br>mark : 3/6/1996<br>terry : 2/29/1996<br>mark : 2/5/1996<br>terry : 1/30/1996<br>mark : 10/10/1995<br>terry : 9/29/1995<br>carol : 12/7/1994<br>jason : 6/28/1994<br>carol : 9/30/1993
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 156225
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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LAMININ, ALPHA-2; LAMA2
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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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<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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LAMININ 2, HEAVY CHAIN
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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MEROSIN, INCLUDED
|
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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LAMININ 2, INCLUDED<br />
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LAMININ M, INCLUDED; LAMM, INCLUDED
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</span>
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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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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: LAMA2</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 111503008, 787037000;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 6q22.33
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:128,883,138-129,516,566 </span>
|
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</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
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<th>
|
|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
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</tr>
|
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</thead>
|
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<tbody>
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
|
6q22.33
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Muscular dystrophy, congenital, merosin deficient or partially deficient
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
607855
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
3
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Muscular dystrophy, limb-girdle, autosomal recessive 23
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
618138
|
|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>The LAMA2 gene encodes the alpha-2 laminin subunit of the heterotrimeric extracellular protein laminin-211, also referred to as laminin-2 or merosin. The other subunits include beta-1 (LAMB1; 150240), and gamma-1, formerly called beta-2 (LAMC1; 150290). Laminin-211 binds to the glycosylated residues of alpha-dystroglycan (DAG1; 128239) in skeletal muscle fibers. Laminin-211 is also expressed in a variety of other tissues, most importantly in Schwann cells in peripheral nerves and in the brain (summary by Oliveira et al., 2018). </p>
|
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</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>Merosin is a protein specifically found in the basement membranes of striated muscle and Schwann cells. It is also found in the basement membrane of placental trophoblasts. Ehrig et al. (1990) compared merosin with laminin, which is thought to be present in all basement membranes. They found that a cDNA clone derived from a merosin fragment contained a 3.4-kb open reading frame encoding 1,130 amino acids. The deduced amino acid sequence of the merosin polypeptide is similar to that of the C-terminal region of the laminin alpha-1 chain. The sequence identity between merosin and laminin is nearly 40% in this region. Like laminin, merosin is associated with the light chains laminin B1 and laminin B2, and the whole molecule has a cross-like structure similar to that of laminin. The authors estimated that the LAMA2 chain is at least 380 kD. </p><p>Vuolteenaho et al. (1994) determined the primary structure of the laminin M chain (symbolized LAMM by them) from cDNA clones isolated from human placental libraries. The complete chain contains a 22-residue signal peptide and 3,088 residues of the mature M chain (3110 residues total). The M chain has a domain structure similar to that of the human and mouse A chains. Northern blot analysis of human fetal tissues showed that the M chain was expressed in most tissues, but not in liver, thymus, or bone. In situ hybridization localized the expression of the M chain gene to cells of mesenchymal origin. In contrast, expression of the A chain was observed only in kidney, testis, neuroretina, and some regions of the brain, as determined by Northern analyses. Epithelial and endothelial cells were negative for both M and A chain gene transcripts. </p><p>Pegoraro et al. (2000) identified a novel alternatively spliced isoform of LAMA2. Direct sequencing showed that the isoform has a 138-bp in-frame deletion from nucleotides 4629 to 4766 of the coding sequence corresponding to about 70% of exon 31. This splicing event removes 46 amino acids in the cysteine-rich domain IIIa, just proximal to the triple coiled-coil region that associates with the beta-1 and gamma-1 chains of laminin. Immunofluorescent studies suggested that this isoform may impair proper laminin chain assembly. </p><p>The LAMA2 protein undergoes posttranslational processing and is cleaved at residue 2580 to yield an N-terminal 300-kD peptide and a C-terminal 80-kD peptide, which are subsequently connected through a noncovalent process (summary by Oliveira et al., 2018). </p>
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Arahata et al. (1993) indicated that merosin is the same as laminin M, a striated muscle-specific, basal-lamina-associated protein. They found that the protein was reduced in the muscle fibers in Fukuyama congenital muscular dystrophy (253800), suggesting that it may play a primary role in the pathogenesis of that disorder. </p><p>The laminin alpha-2 subunit is expressed in Schwann cells. Ng et al. (2000) provided evidence for the involvement of the specific trisaccharide unit of the phenolic glycolipid-1 (PGL1) of Mycobacterium leprae (see 246300) in determining the bacterial predilection to the peripheral nerve. PGL1 binds specifically to the native laminin-2 in the basal lamina of Schwann cell-axon units. This binding is mediated by the LG1, LG4, and LG5 modules present in the naturally cleaved fragments of the peripheral nerve LAMA2 chain, and is inhibited by the synthetic terminal trisaccharide of PGL1. PGL1 is involved in the M. leprae invasion of Schwann cells through the basal lamina in a laminin-2-dependent pathway. The results indicated a novel role of a bacterial glycolipid in determining the nerve predilection of a human pathogen. </p>
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Zhang et al. (1996) determined the genomic structure of the human LAMA2 gene. The gene spans over 260 kb and contains 64 exons. Two of the exons are unusually small, being 6 and 12 bp, respectively. </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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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Vuolteenaho et al. (1994) localized the human LAMA2 gene to 6q22-q23 by a combination of somatic cell hybrid analysis and in situ hybridization. </p><p>By FISH, Sallinen et al. (1999) mapped the mouse Lama2 gene to chromosome 10A4-B1. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Muscular Dystrophy, Congenital Merosin-Deficient, Type 1A</em></strong></p><p>
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In affected members of 2 families with congenital merosin-deficient muscular dystrophy type 1A (MDC1A; 607855), 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. Except for one, each of the gene changes identified was novel, including 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 the 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 the 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 from 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><p><strong><em>Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 23</em></strong></p><p>
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In 5 patients from 4 families with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; 618138), Gavassini et al. (2011) identified homozygous or compound heterozygous mutations in the LAMA2 gene (see, e.g., 156225.0016 and 156225.0017). There were 4 missense mutations, 1 splice site mutation, and 1 in-frame deletion. The mutations were located in both the globular and the rod-like domains of the protein. Functional studies of the variants were not performed, but the splice site mutation was confirmed to result in a frameshift in patient cells. Muscle biopsy showed partial LAMA2 deficiency in all patients. </p><p>In a girl with LGMDR23, Chan et al. (2014) identified compound heterozygous mutations in the LAMA2 gene (Q131X, 156225.0018 and A1496V, 156225.0019). The mutations segregated with the disorder in the family. Functional studies of the variants were not performed. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>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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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gawlik et al. (2004) generated mice expressing a Lama1 transgene in skeletal muscle of Lama2-deficient mice. Lama1 is not normally expressed in muscle, but transgenic Lama1 was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains (LAMA4, 600133; LAMB2, 150325). In 4-month-old mice, Lama1 could fully prevent development of muscular dystrophy in several muscles, and partially in others. Gawlik et al. (2004) concluded that the Lama1 transgene not only reversed the appearance of histopathologic features of the disease to a remarkable degree, but also greatly improved health and longevity of the mice. </p><p>Dominov et al. (2005) generated mdx (300377) or Lama2-null mice that also overexpressed muscle-specific human BCL2 (151430). In mdx mice, overexpression of BCL2 failed to produce any significant differences in muscle pathology; however, in Lama2-null mice, muscle-specific overexpression of BCL2 led to a several-fold increase in life span and an increased growth rate. Dominov et al. (2005) concluded that BCL2-mediated apoptosis appeared to play a significant role in pathogenesis of congenital muscular dystrophy type 1A due to LAMA2 deficiency but not in Duchenne muscular dystrophy (DMD; 310200) due to dystrophin deficiency. </p><p>In mice, Millay et al. (2008) showed the deletion of the gene encoding cyclophilin D, Ppif (604486), rendered mitochondria largely insensitive to the calcium overload-induced swelling associated with a defective sarcolemma, thus reducing myofiber necrosis in 2 distinct models of muscular dystrophy. Mice lacking delta-sarcoglycan (Scgd-null mice; see 601411) showed markedly less dystrophic disease in both skeletal muscle and heart in the absence of Ppif. Moreover, the premature lethality associated with deletion of Lama2 was rescued, as were other indices of dystrophic disease. Treatment with the cyclophilin inhibitor Debio-025 similarly reduced mitochondrial swelling and necrotic disease manifestations in mdx mice, a model of Duchenne muscular dystrophy, and in Scgd-null mice. Thus, mitochondrial-dependent necrosis represents a prominent disease mechanism in muscular dystrophy, suggesting that inhibition of cyclophilin D could provide a new pharmacologic treatment strategy for these diseases. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>19 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, IVS30, A-T, -2
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<br />
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SNP: rs1554278541,
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ClinVar: RCV000671265
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a family with merosin-deficient congenital muscular dystrophy (607855), Helbling-Leclerc et al. (1995) found a 193-bp deletion corresponding to all of exon 31 of the gene. From the sequence of flanking introns, they found an A-to-T transversion at the -2 position of the consensus acceptor splice site of exon 31. Two affected CMD children were homozygous, while their parents and sibs were heterozygous. The mutation occurred 2 nucleotides to the 5-prime side of NT4573. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0002 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, GLN1241TER
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<br />
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SNP: rs121913569,
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ClinVar: RCV000015360, RCV000790720, RCV000818341, RCV003225924
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of a nonconsanguineous family with congenital merosin-deficient muscular dystrophy (607855), Helbling-Leclerc et al. (1995) found by SSCP analysis aberrant conformers for exon 24 of the LAMA2 gene. Sequencing of exon 24 revealed a homozygous C-to-T substitution at position 3767 of their cDNA. The mutation caused a change in a CAA codon for glutamine to a TAA stop codon (Q1241X) in domain IVa. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0003 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, IVS25, T-C, +2
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<br />
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SNP: rs1554269966,
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|
ClinVar: RCV000015363, RCV000518321, RCV000853232, RCV000985057, RCV001857909, RCV004527387
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 sibs with mild congenital merosin-deficient muscular dystrophy (607855) in a consanguineous Saudi Arabian family, Allamand et al. (1997) found that the laminin alpha-2 chain had an internal deletion as the result of a splice site mutation in the LAMA2 gene that caused the splicing out of exon 25. The predicted protein lacked 63 amino acids in domain IVa, which forms a globular structure on the short arm of the alpha-2 chain. Antibodies against the G-domain of the laminin alpha-2 chain showed a near normal expression in skeletal muscle, whereas antibodies against the N-terminal region showed a drastic reduction. These patients appeared mildly affected compared to others who completely lacked this protein. Allamand et al. (1997) compared the situation to Becker muscular dystrophy (300376), in which in-frame deletions of the dystrophin gene (300377) result in the expression of a semifunctional protein and leads to a mild phenotype. The splice site mutation was a T-to-C transition at position +2 of the consensus donor splice site of exon 25. This mutation was found in homozygous state in both patients and induced the splicing out of exon 25 by alternately using the donor splice site of exon 24. Both parents were heterozygous. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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|
<span class="mim-font">
|
|
<strong>.0004 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, LEU2564PRO
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<br />
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|
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SNP: rs121913570,
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|
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gnomAD: rs121913570,
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|
|
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ClinVar: RCV000015364, RCV003330391
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with congenital merosin-deficient muscular dystrophy (607855) characterized by difficulty walking, hypotonia, proximal weakness, hyporeflexia, and white matter hypodensity on MRI, He et al. (2001) identified compound heterozygosity in the LAMA2 gene: a missense mutation resulting in a leu2564-to-pro (L2564P) substitution and a nonsense mutation at codon 3085 (R3085X; 156225.0005). Laminin alpha-2 antibody labeling was mildly reduced. He et al. (2001) suggested that the patient's mild phenotype correlated with partial deficiency of laminin alpha-2 due to expression of the L2564P allele. The authors noted the importance of using antibodies against different domains of the protein for correct immunohistochemical characterization. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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|
LAMA2, ARG3085TER
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|
<br />
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|
|
SNP: rs121913571,
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|
|
|
gnomAD: rs121913571,
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|
|
|
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ClinVar: RCV000015361, RCV000228823, RCV000521505, RCV003574700, RCV005042055
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</span>
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</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>For discussion of the arg3085-to-ter (R3085X) substitution in the LAMA2 gene that was found in compound heterozygous state in a patient with congenital merosin-deficient muscular dystrophy (607855) by He et al. (2001), see 156225.0004. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, 1-BP DEL, 8314A
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<br />
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ClinVar: RCV000015362
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</span>
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</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In a patient with congenital merosin-deficient muscular dystrophy (607855) characterized by motor delay with inability to walk, hypotonia, scoliosis, contractures, seizures, and white matter hypodensity on MRI, He et al. (2001) identified a homozygous 1-bp deletion (8314delA) in the LAMA2 gene, resulting in a frameshift and premature stop codon. He et al. (2001) suggested that the reduced amount of the truncated protein correlated with the severe phenotype. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, 2-BP DEL, 2098AG
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<br />
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|
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SNP: rs202247790,
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ClinVar: RCV000031899, RCV000078754, RCV000200517, RCV000230453, RCV000557045, RCV004813047, RCV005031466
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a patient with congenital merosin-deficient muscular dystrophy (607855) characterized by inability to walk, kyphoscoliosis, contractures, chest deformity, respiratory insufficiency, and white matter hypodensity on MRI, He et al. (2001) identified a 2-bp deletion (2098delAG) in the LAMA2 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, ARG2578TER
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<br />
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SNP: rs121913572,
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gnomAD: rs121913572,
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ClinVar: RCV000015366, RCV000763556, RCV000790757, RCV001068136, RCV001794447, RCV002288491, RCV002513061, RCV004532360
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Coral-Vazquez et al. (2003) reported the case of an 8-month-old Mexican female, from a consanguineous family, with classic merosin-deficient congenital muscular dystrophy (607855). In addition to elevated serum creatine kinase and dystrophic changes on muscle biopsy, there were abnormalities on brain MRI. Immunofluorescence analysis demonstrated complete absence of LAMA2. In contrast, all components of the dystrophin-glycoprotein complex appeared normal. Mutation analysis of the LAMA2 gene identified a homozygous 7781C-T transition in exon 54 that resulted in an arg2578-to-ter (R2578X) mutation in the G domain of the protein. Both parents and some other relatives were carriers of the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0009 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LAMA2, CYS862ARG
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<br />
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SNP: rs121913573,
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ClinVar: RCV000015367, RCV000287266, RCV001239611
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with congenital muscular dystrophy and partial LAMA2 deficiency (607855), Tezak et al. (2003) found compound heterozygosity for a 2633T-C transition in exon 18 of the LAMA2 gene, resulting in a change of a conserved cysteine residue at codon 862 to arg (C862R), and another mutation that caused abnormalities of transcription but was not fully characterized. This patient reached the ability to walk unsupported, in contrast with patients with complete LAMA2 deficiency CMD who never achieve this ability. In her late teens, she began to lose previously acquired cognitive abilities. Although mental retardation had previously been reported in CMDs, dementia was unusual. A possible explanation is ascertainment bias, since most of the CMD patients reported were studied at a young age, while dementia may develop at a later stage of the disease. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
|
|
</span>
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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LAMA2, CYS527TYR
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<br />
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|
SNP: rs121913574,
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|
|
gnomAD: rs121913574,
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|
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ClinVar: RCV000015368, RCV000078747, RCV000822637
|
|
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|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a patient with congenital muscular dystrophy and partial LAMA2 deficiency (607855), Tezak et al. (2003) found compound heterozygosity for a 1629G-A transition in exon 10 of the LAMA2 gene, resulting in a change of a conserved cysteine residue at codon 527 to tyr (C527Y), and a second mutation that caused transcription abnormalities but was not fully characterized. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
LAMA2, ARG1549TER
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<br />
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SNP: rs121913575,
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|
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gnomAD: rs121913575,
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|
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|
|
|
ClinVar: RCV000015369, RCV000674731, RCV001203616
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
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|
<span class="mim-text-font">
|
|
<p>In a patient with congenital muscular dystrophy and partial LAMA2 deficiency (607855), Pegoraro et al. (2000) identified compound heterozygosity for 2 mutations in the LAMA2 gene: a 4694C-T transition in exon 31, resulting in an arg1549-to-ter (R1549X) substitution, and a 7196C-T transition in exon 49, resulting in an arg2383-to-ter (R2383X; 156225.0012) substitution. The patient had a severe form of the disorder with central nervous system involvement including seizures, mental retardation, ventricular dilatation, and pachygyria. Each parent was heterozygous for 1 of the mutations. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MUSCULAR DYSTROPHY, CONGENITAL, DUE TO PARTIAL LAMA2 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
LAMA2, ARG2383TER
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|
<br />
|
|
|
|
SNP: rs121913576,
|
|
|
|
|
|
gnomAD: rs121913576,
|
|
|
|
|
|
ClinVar: RCV000015370, RCV000179066, RCV000654712, RCV000790693, RCV002444431, RCV002476971
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 7196C-T transition in exon 49 of the LAMA2 gene, resulting in an arg2383-to-ter (R2383X) substitution, that was found in a patient with congenital muscular dystrophy and partial LAMA2 deficiency (607855) by Pegoraro et al. (2000), see 156225.0011. </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
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|
<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, CYS967TER
|
|
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|
<br />
|
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|
|
SNP: rs121913577,
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|
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|
|
|
gnomAD: rs121913577,
|
|
|
|
|
|
ClinVar: RCV000015371, RCV000824626, RCV001091209
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with congenital merosin-deficient muscular dystrophy (MDC1A; 607855), Di Blasi et al. (2005) identified a 2901C-A transversion in exon 21 of the LAMA2 gene, resulting in a cys967-to-ter (C967X) substitution and truncation of the protein in domain IIIb. One of the patients, who was Italian, was homozygous for the C967X mutation, and the other patient, from Albania, was compound heterozygous for the C967X mutation and a 1-bp deletion (825delC) in exon 6 of the LAMA2 gene, resulting in a frameshift and premature stop codon. The C967X mutation had previously been reported in affected members of 2 Italian families originating from the southern Adriatic coast (Guicheney et al., 1998). Haplotype analysis suggested a remote founder effect, with the mutation most likely originating in Albania. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, 1-BP DEL, 825C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1562275792,
|
|
|
|
|
|
|
|
ClinVar: RCV000015372
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion (825delC) in exon 6 of the LAMA2 gene, resulting in a frameshift and premature stop codon, that was found in compound heterozygous state in 2 unrelated patients with congenital merosin-deficient muscular dystrophy by Di Blasi et al. (2005), see 156225.0013. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, 5-KB DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000015373
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 8 patients with MDC1A (607855), Oliveira et al. (2008) identified a 5-kb deletion encompassing exon 56 of the LAMA2. Two patients were homozygous for the deletion, and 6 were compound heterozygous with another pathogenic LAMA2 mutation. The deletion was detected in 31% of 26 patients with the disorder. Although all patients were of Spanish or Portuguese descent, no common haplotypes were found. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 23</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, LEU243PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1562273395,
|
|
|
|
|
|
|
|
ClinVar: RCV000709617, RCV003465646
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs (patients 2 and 3) with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; 618138), Gavassini et al. (2011) identified compound heterozygous mutations in the LAMA2 gene: a c.728T-C transition in exon 5, resulting in a leu243-to-pro (L243P) substitution at a highly conserved residue in protein domain VI, and a complex splice site mutation in intron 33 (c.4860+2T-G_4860+3insGCC; 156225.0017), resulting in a splice site alteration, a frameshift, and premature termination (Phe1573_Lys1620delinsSerfsTer49). The splice site defect was confirmed by analysis of patient cells. Additional functional studies were not performed, but muscle biopsy showed partial LAMA2 deficiency. Expression of LAMA5 (601033) was increased. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 23</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, IVS33, c.4860+2T-G_4860+3insGCC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1562497781,
|
|
|
|
|
|
|
|
ClinVar: RCV000709618
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the complex splice site mutation in intron 33 of the LAMA2 gene (c.4860+2T-G_4860+3insGCC), resulting in a splice site alteration, a frameshift, and premature termination (Phe1573_Lys1620delinsSerfsTer49), that was found in compound heterozygous state in 2 sibs with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; 618138) by Gavassini et al. (2011), see 156225.0016. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 23</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, GLN131TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1562200866,
|
|
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|
|
|
|
|
ClinVar: RCV000709619, RCV001861944
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old girl with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; 618138), Chan et al. (2014) identified compound heterozygous mutations in the LAMA2 gene: a c.391C-T transition in exon 3, resulting in a gln131-to-ter (Q131X) substitution, and a c.4487C-T transition in exon 31, resulting in an ala1496-to-val (A1496V; 156225.0019) substitution. The Q131X mutation, which was inherited from the unaffected mother, occurred in domain VI of the protein, whereas the A1496V mutation, which was inherited from the unaffected father, occurred in domain IIIa of the protein. The patient also carried a heterozygous variant of unknown significance in the LAMA2 gene (C199S) that was inherited from the father. Functional studies of the variants were not performed, but skeletal muscle biopsy from the patient showed decreased LAMA2 in muscle fibers and in intramuscular motor nerves. Expression of LAMA5 (601033) was increased. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 23</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LAMA2, ALA1496VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs147077184,
|
|
|
|
|
|
gnomAD: rs147077184,
|
|
|
|
|
|
ClinVar: RCV000194655, RCV000509423, RCV000659062, RCV000709620, RCV001081183, RCV001152676, RCV004537432
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.4487C-T transition in exon 31 of the LAMA2 gene, resulting in an ala1496-to-val (A1496V) substitution, that was found in compound heterozygous state in a patient with autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23; 618138) by Chan et al. (2014), see 156225.0018. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
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|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Cassandra L. Kniffin - updated : 10/04/2018<br>Cassandra L. Kniffin - updated : 2/23/2009<br>Ada Hamosh - updated : 6/11/2008<br>George E. Tiller - updated : 2/7/2008<br>George E. Tiller - updated : 1/16/2007<br>Cassandra L. Kniffin - updated : 10/9/2006<br>Cassandra L. Kniffin - updated : 6/5/2006<br>Victor A. McKusick - updated : 3/7/2003<br>Victor A. McKusick - updated : 3/6/2003<br>Cassandra L. Kniffin - updated : 12/3/2002<br>Michael J. Wright - updated : 7/30/2002<br>Ada Hamosh - updated : 9/21/2001<br>Carol A. Bocchini - updated : 2/15/2001<br>Stylianos E. Antonarakis - updated : 11/21/2000<br>Victor A. McKusick - updated : 1/12/2000<br>Victor A. McKusick - updated : 6/3/1999<br>Victor A. McKusick - updated : 10/8/1998<br>Victor A. McKusick - updated : 9/30/1998<br>Victor A. McKusick - updated : 6/23/1997<br>Victor A. McKusick - updated : 5/19/1997<br>Jennifer P. Macke - updated : 4/24/1997<br>Orest Hurko - edited : 4/13/1996<br>Orest Hurko - updated : 4/4/1996<br>Orest Hurko - updated : 3/9/1996<br>Orest Hurko - updated : 3/6/1996<br>Orest Hurko - updated : 2/5/1996<br>Orest Hurko - updated : 8/15/1995
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