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Entry
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- *608455 - GLYCOGEN PHOSPHORYLASE, MUSCLE; PYGM
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- OMIM
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<p>
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<span class="h4">*608455</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#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/608455">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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<a href="#contributors"><strong>Contributors</strong></a>
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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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</ul>
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<div id="mimFloatingLinksMenu">
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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 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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<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=ENSG00000068976;t=ENST00000164139" 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=5837" 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=608455" 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=ENSG00000068976;t=ENST00000164139" 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_001164716,NM_005609" 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_005609" 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=608455" 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=01986&isoform_id=01986_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/PYGM" 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/187595,190784,1335270,2232007,3041717,3153910,5032009,116496789,119594690,119594691,120660402,189069413,193786479,194387906,194388822,257900462,925169867" 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/P11217" 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=5837" 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=ENSG00000068976;t=ENST00000164139" 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=PYGM" 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=PYGM" 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+5837" 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/PYGM" 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:5837" 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/5837" 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=chr11&hgg_gene=ENST00000164139.4&hgg_start=64746389&hgg_end=64760715&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://medlineplus.gov/genetics/gene/pygm" 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=608455[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=608455[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://gnomad.broadinstitute.org/gene/ENSG00000068976" 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=PYGM" 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=PYGM" 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=PYGM" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PYGM&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/PA34069" 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:9726" 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/FBgn0004507.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:97830" 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/PYGM#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:97830" 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/5837/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/OMIA001139/" 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=5837" 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=WBGene00020696;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-040426-1206" 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="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:5837" 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=PYGM&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> 55912009<br />
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<strong>ICD10CM:</strong> E74.04<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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608455
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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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GLYCOGEN PHOSPHORYLASE, MUSCLE; PYGM
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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">
|
|
MYOPHOSPHORYLASE
|
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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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<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=PYGM" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PYGM</a></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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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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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: <a href="/geneMap/11/558?start=-3&limit=10&highlight=558">11q13.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:64746389-64760715&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'})">11:64,746,389-64,760,715</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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</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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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
|
Location
|
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</th>
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<th>
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|
Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
|
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
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</thead>
|
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<tbody>
|
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/558?start=-3&limit=10&highlight=558">
|
|
11q13.1
|
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</a>
|
|
</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
McArdle disease
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/232600"> 232600 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/608455" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608455" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
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<p>The PYGM gene encodes the muscle isoform of glycogen phosphorylase (<a href="https://enzyme.expasy.org/EC/2.4.1.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.4.1.1</a>), which catalyzes and regulates the breakdown of glycogen to glucose-1-phosphate during glycogenolysis. This metabolic pathway is necessary for the generation of ATP during physical activity (<a href="#10" class="mim-tip-reference" title="Gautron, S., Daegelen, D., Mennecier, F., Dubocq, D., Kahn, A., Dreyfus, J.-C. <strong>Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency).</strong> J. Clin. Invest. 79: 275-281, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3466902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3466902</a>] [<a href="https://doi.org/10.1172/JCI112794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3466902">Gautron et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3466902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#10" class="mim-tip-reference" title="Gautron, S., Daegelen, D., Mennecier, F., Dubocq, D., Kahn, A., Dreyfus, J.-C. <strong>Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency).</strong> J. Clin. Invest. 79: 275-281, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3466902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3466902</a>] [<a href="https://doi.org/10.1172/JCI112794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3466902">Gautron et al. (1987)</a> isolated muscle phosphorylase cDNA clones from a human cDNA library. Northern blot experiments revealed 1 specific mRNA of 3.4 kb found uniquely in tissues expressing muscle phosphorylase. The muscle glycogen phosphorylase protein comprises 842 amino acids (<a href="#14" class="mim-tip-reference" title="Kubisch, C., Wicklein, E. M., Jentsch, T. J. <strong>Molecular diagnosis of McArdle disease: revised genomic structure of the myophosphorylase gene and identification of a novel mutation.</strong> Hum. Mutat. 12: 27-32, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9633816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9633816</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:1<27::AID-HUMU4>3.0.CO;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9633816">Kubisch et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3466902+9633816" 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="#4" class="mim-tip-reference" title="Burke, J., Hwang, P., Anderson, L., Lebo, R., Gorin, F., Fletterick, R. <strong>Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase.</strong> Proteins 2: 177-187, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3447177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3447177</a>] [<a href="https://doi.org/10.1002/prot.340020303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3447177">Burke et al. (1987)</a> determined the intron/exon structure of the PYGM gene. <a href="#14" class="mim-tip-reference" title="Kubisch, C., Wicklein, E. M., Jentsch, T. J. <strong>Molecular diagnosis of McArdle disease: revised genomic structure of the myophosphorylase gene and identification of a novel mutation.</strong> Hum. Mutat. 12: 27-32, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9633816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9633816</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:1<27::AID-HUMU4>3.0.CO;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9633816">Kubisch et al. (1998)</a> provided a revised genomic structure for the PYGM gene, which contains 20 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3447177+9633816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#16" class="mim-tip-reference" title="Lebo, R. V., Gorin, F., Fletterick, R. J., Kao, F.-T., Cheung, M.-C., Bruce, B. D., Kan, Y. W. <strong>High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome to chromosome 11.</strong> Science 225: 57-59, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6587566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6587566</a>] [<a href="https://doi.org/10.1126/science.6587566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6587566">Lebo et al. (1984)</a> used an improved method of chromosome sorting to assign the gene for skeletal muscle glycogen phosphorylase to chromosome 11. The method used a double laser system to sort chromosomes into 21 groups. A clone of the carboxy-terminal region of the myophosphorylase gene hybridized to a spot containing chromosomes 10, 11, and 12. Using chromosomes from cell lines with translocations of various ones of these 3 chromosomes, including a 4;11 reciprocal translocation, they assigned the gene to 11p13-qter. This location was confirmed by testing a series of Chinese hamster-human somatic cell hybrid DNAs that contained a single human chromosome 11 with various terminal deletions. <a href="#15" class="mim-tip-reference" title="Lebo, R. V., Anderson, L. A., DiMauro, S., Lynch, E., Hwang, P., Fletterick, R. <strong>Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence.</strong> Hum. Genet. 86: 17-24, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1701414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1701414</a>] [<a href="https://doi.org/10.1007/BF00205166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1701414">Lebo et al. (1990)</a> further sublocalized the PYGM gene to the proximal part of band 11q13 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6587566+1701414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Glaser, T., Matthews, K. E., Hudson, J. W., Seth, P., Housman, D. E., Crerar, M. M. <strong>Localization of the muscle, liver and brain glycogen phosphorylase genes on linkage maps of mouse chromosomes 19, 12 and 2, respectively.</strong> Genomics 5: 510-521, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2575583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2575583</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90017-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2575583">Glaser et al. (1989)</a> mapped the muscle, liver, and brain phosphorylases (Pygm, Pygl, and Pygb) to mouse chromosomes 19, 12, and 2, respectively, by comparing segregations patterns of RFLPs with those of previously mapped genetic markers in an interspecies backcross between Mus musculus domesticus and Mus spretus. A previously mapped 'muscle-deficient' mutation in the mouse (mdf) was found to be closely linked to the muscle phosphorylase gene. However, since muscle phosphorylase gene structure and expression appeared to be unaltered in homozygous mdf/mdf mice, this mutation was determined not to be a model of McArdle disease (<a href="/entry/232600">232600</a>), which is caused by mutation in the PYGM gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2575583" 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="Courseaux, A., Grosgeorge, J., Gaudray, P., Pannett, A. A. J., Forbes, S. A., Williamson, C., Bassett, D., Thakker, R. V., Teh, B. T., Farnebo, F., Shepherd, J., Skogseid, B., Larsson, C., Giraud, S., Zhang, C. X., Salandre, J., Calender, A. <strong>Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13.</strong> Genomics 37: 354-365, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8938448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8938448</a>]" pmid="8938448">Courseaux et al. (1996)</a> used a combination of methods to refine maps of the approximately 5-Mb region of 11q13 that includes multiple endocrine neoplasia type 1 (MEN1; <a href="/entry/131100">131100</a>). They proposed the following gene order: cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM, ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8938448" 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>Among 94 enzyme-probe combinations, <a href="#15" class="mim-tip-reference" title="Lebo, R. V., Anderson, L. A., DiMauro, S., Lynch, E., Hwang, P., Fletterick, R. <strong>Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence.</strong> Hum. Genet. 86: 17-24, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1701414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1701414</a>] [<a href="https://doi.org/10.1007/BF00205166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1701414">Lebo et al. (1990)</a> identified a single MspI polymorphism in the PYGM gene region. This polymorphism and an insertion/deletion polymorphism more 3-prime to the gene were found to be informative in 75% of patients at risk for myophosphorylase deficiency, or McArdle disease (GSD5; <a href="/entry/232600">232600</a>). <a href="#15" class="mim-tip-reference" title="Lebo, R. V., Anderson, L. A., DiMauro, S., Lynch, E., Hwang, P., Fletterick, R. <strong>Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence.</strong> Hum. Genet. 86: 17-24, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1701414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1701414</a>] [<a href="https://doi.org/10.1007/BF00205166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1701414">Lebo et al. (1990)</a> noted that the scarcity of polymorphic sites in the PYGM gene contrasted sharply with the situation with the liver phosphorylase gene (PYGL; <a href="/entry/613741">613741</a>), the site of the mutation in glycogen storage disease VI (<a href="/entry/232700">232700</a>); in the case of PYGL, they found 6 polymorphic sites in 15 enzyme-probe combinations. <a href="#12" class="mim-tip-reference" title="Iwasaki, H., Stewart, P. W., Dilley, W. G., Holt, M. S., Steinbrueck, T. D., Wells, S. A., Jr., Donis-Keller, H. <strong>A minisatellite and a microsatellite polymorphism within 1.5 kb at the human muscle glycogen phosphorylase (PYGM) locus can be amplified by PCR and have combined informativeness of PIC 0.95.</strong> Genomics 13: 7-15, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349582</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90194-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349582">Iwasaki et al. (1992)</a> described highly informative minisatellite and microsatellite polymorphisms at the PYGM locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1349582+1701414" 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 study of 40 patients with McArdle disease, <a href="#25" class="mim-tip-reference" title="Tsujino, S., Shanske, S., DiMauro, S. <strong>Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease).</strong> New Eng. J. Med. 329: 241-245, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8316268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8316268</a>] [<a href="https://doi.org/10.1056/NEJM199307223290404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8316268">Tsujino et al. (1993)</a> identified 3 distinct point mutations in the PYGM gene (<a href="#0001">608455.0001</a>-<a href="#0003">608455.0003</a>). One of these mutations, arg50-to-ter (R50X; <a href="#0001">608455.0001</a>), was present in 75% of patients in heterozygous or homozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8316268" 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="#1" class="mim-tip-reference" title="Andreu, A. L., Nogales-Gadea, G., Cassandrini, D., Arenas, J., Bruno, C. <strong>McArdle disease: molecular genetic update.</strong> Acta Myol. 26: 53-57, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17915571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17915571</a>]" pmid="17915571">Andreu et al. (2007)</a> provided an update of the molecular genetics of McArdle disease, noting that over 65 mutations in the PYGM gene had been identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17915571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Nogales-Gadea, G., Rubio, J. C., Fernandez-Cadenas, I., Garcia-Consuegra, I., Lucia, A., Cabello, A., Garcia-Arumi, E., Arenas, J., Andreu, A. L., Martin, M. A. <strong>Expression of the muscle glycogen phosphorylase gene in patients with McArdle disease: the role of nonsense-mediated mRNA decay.</strong> Hum. Mutat. 29: 277-283, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994553</a>] [<a href="https://doi.org/10.1002/humu.20649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994553">Nogales-Gadea et al. (2008)</a> found that 26 (92%) of 28 Spanish patients with McArdle disease showed nonsense-mediated decay (NMD) of their mutant PYGM mRNA transcript, corresponding mainly to mutations resulting in premature termination codons. R50X was the most common mutation in this cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Garcia-Consuegra, I., Rubio, J. C., Nogales-Gadea, G., Bautista, J., Jimenez, S., Cabello, A., Lucia, A., Andreu, A. L., Arenas, J., Martin, M. A. <strong>Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA.</strong> J. Med. Genet. 46: 198-202, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19251976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19251976</a>] [<a href="https://doi.org/10.1136/jmg.2008.059469" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19251976">Garcia-Consuegra et al. (2009)</a> used skeletal muscle mRNA and cDNA analysis to identify a second defect in the PYGM gene in 4 patients with McArdle disease in whom heterozygous PYGM mutations were initially detected by genomic DNA analysis. They identified a large deletion and splice site mutation in 1 patient each and a synonymous (K215K) substitution in exon 5 in 2 patients. Real-time PCR of muscle from 1 patient with the K215K substitution showed a drastic decrease in mRNA, implicating nonsense-mediated mRNA decay as a mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19251976" 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 5 unrelated patients with McArdle disease, <a href="#30" class="mim-tip-reference" title="Wu, Y., Weber, J. L., Vladutiu, G. D., Tarnopolsky, M. A. <strong>Six novel mutations in the myophosphorylase gene in patients with McArdle disease and a family with pseudo-dominant inheritance pattern.</strong> Molec. Genet. Metab. 104: 587-591, 2011. Note: Erratum: Molec. Genet. Metab. 111: 539 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21880526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21880526</a>] [<a href="https://doi.org/10.1016/j.ymgme.2011.08.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21880526">Wu et al. (2011)</a> identified compound heterozygosity for the common R50X mutation and another pathogenic mutation in the PYGM gene (see, e.g., D51G, <a href="#0020">608455.0020</a>). A sixth patient was homozygous for a small deletion (<a href="#0021">608455.0021</a>). All had typical features of the disorder, including exercise intolerance, decreased or absent PYGM activity and immunostaining in muscle samples, and increased serum creatine kinase. Three had rhabdomyolysis and myoglobinuria. Muscle biopsy of 5 patients showed glycogen accumulation. Although the median age at diagnosis was 29.5 years, most recalled having onset of symptoms in childhood or adolescence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21880526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#28" class="mim-tip-reference" title="Vissing, J., Duno, M., Schwartz, M., Haller, R. G. <strong>Splice mutations preserve myophosphorylase activity that ameliorates the phenotype in McArdle disease.</strong> Brain 132: 1545-1552, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433441</a>] [<a href="https://doi.org/10.1093/brain/awp065" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433441">Vissing et al. (2009)</a> reported 2 unrelated patients, aged 30 and 39 years, respectively, with a mild form of McArdle disease (<a href="/entry/232600">232600</a>) caused by compound heterozygosity for PYGM mutation. Each patient carried 1 typical mutation (R50X, <a href="#0001">608455.0001</a>; G205S, <a href="#0002">608455.0002</a>) and 1 splice site mutation (<a href="#0018">608455.0018</a> and <a href="#0019">608455.0019</a>). The splice site mutations were found to cause aberrant splicing and production of abnormally spliced proteins that were expressed in small amounts. Biochemical studies showed 1.0 to 2.5% residual PYGM activity, suggesting that the mutations were 'leaky' and allowed some normally spliced products to be generated. Both patients reported muscle cramps, pain, and episodes of rhabdomyolysis and myoglobinuria after exercise. One had 2 to 3 episodes, whereas the other had more than 10 with 1 episode of renal failure. Both also had increased serum creatine kinase, similar to patients with typical disease. However, both patients also had a high capacity for sustained exercise. Exercise testing showed an intermediate phenotype between controls and individuals with typical McArdle disease. The patients could complete 60 minutes of ischemic exercise before muscle cramping occurred, and peak oxidative capacity was about 2-fold higher compared to patients with typical McArdle disease. The findings indicated that very low levels of PYGM are sufficient to sustain glycogenolysis and muscle oxidative metabolism, and provided the first genotype/phenotype correlation at the molecular level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19433441" 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>Homozygosity for a common stop codon in the ACTN3 gene (R577X; <a href="/entry/102574#0001">102574.0001</a>) results in complete deficiency of the fast fiber muscle protein alpha-actinin-3. This ACTN3 genotype is associated with human athletic performance, and alpha-actinin-3-deficient mice (Actn3 knockout mice) have a shift in the properties of fast muscle fibers toward slower fiber properties, with increased activity of multiple enzymes in the aerobic metabolic pathway and slower contractile properties. Alpha-actinins have been shown to interact with a number of muscle proteins, including the key metabolic regulator glycogen phosphorylase (GPh). <a href="#21" class="mim-tip-reference" title="Quinlan, K. G. R., Seto, J. T., Turner, N., Vandebrouck, A., Floetenmeyer, M., Macarthur, D. G., Raftery, J. M., Lek, M., Yang, N., Parton, R. G., Cooney, G. J., North, K. N. <strong>Alpha-actinin-3 deficiency results in reduced glycogen phosphorylase activity and altered calcium handling in skeletal muscle.</strong> Hum. Molec. Genet. 19: 1335-1346, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20089531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20089531</a>] [<a href="https://doi.org/10.1093/hmg/ddq010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20089531">Quinlan et al. (2010)</a> demonstrated a link between alpha-actinin-3 and glycogen metabolism. Actn3 knockout mice had higher muscle glycogen content and a 50% reduction in the activity of GPh. The reduction in enzyme activity was accompanied by altered posttranslational modification of GPh, suggesting that alpha-actinin-3 may regulate GPh activity by altering its level of phosphorylation. <a href="#21" class="mim-tip-reference" title="Quinlan, K. G. R., Seto, J. T., Turner, N., Vandebrouck, A., Floetenmeyer, M., Macarthur, D. G., Raftery, J. M., Lek, M., Yang, N., Parton, R. G., Cooney, G. J., North, K. N. <strong>Alpha-actinin-3 deficiency results in reduced glycogen phosphorylase activity and altered calcium handling in skeletal muscle.</strong> Hum. Molec. Genet. 19: 1335-1346, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20089531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20089531</a>] [<a href="https://doi.org/10.1093/hmg/ddq010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20089531">Quinlan et al. (2010)</a> proposed that the changes in glycogen metabolism underlie the downstream metabolic consequences of alpha-actinin-3 deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20089531" 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 study of 40 patients with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#25" class="mim-tip-reference" title="Tsujino, S., Shanske, S., DiMauro, S. <strong>Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease).</strong> New Eng. J. Med. 329: 241-245, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8316268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8316268</a>] [<a href="https://doi.org/10.1056/NEJM199307223290404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8316268">Tsujino et al. (1993)</a> identified 3 distinct point mutations in the PYGM gene. The most common mutation was a C-to-T change in exon 1, reported as an ARG49TER (R49X) substitution but now designated R50X. Eighteen patients were homozygous for the R49X mutation, while 12 were compound heterozygous for the R49X mutation and another mutation, thus accounting for 75% of all patients. The second mutation was a G-to-A change in exon 5, resulting in a gly205-to-ser (G205S; <a href="#0002">608455.0002</a>) substitution, reported as a GLY204SER (G204S) substitution. The third mutation was an A-to-C change in exon 14, resulting in a lys543-to-thr (L543T) substitution, reported as a LYS542THR (L542T) substitution. Six of the 40 patients had different mutations in the 2 alleles (i.e., were compound heterozygotes), and 11 were presumed to be compound heterozygotes for a known mutation and an unknown one. Only 5 patients had none of the 3 mutations. In 1 remarkable family, all 3 mutations were present in various combinations in 5 members of the family in which transmission appeared to be autosomal dominant. Thus, this was pseudodominance due to mating of a compound heterozygote with a person carrying a third mutation. Three children were all compound heterozygotes, but compound heterozygotes of 2 different compositions. The mother was a 204/49 compound; the father was a 542 carrier; 2 children were 542/204 compounds and 1 was a 542/49 compound. Presumed autosomal dominant inheritance was reported by <a href="#5" class="mim-tip-reference" title="Chui, L. A., Munsat, T. L. <strong>Dominant inheritance of McArdle syndrome.</strong> Arch. Neurol. 33: 636-641, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1067063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1067063</a>] [<a href="https://doi.org/10.1001/archneur.1976.00500090042008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1067063">Chui and Munsat (1976)</a>, and the occurrence of McArdle disease in 2 generations was attributed to manifestations in some heterozygotes by <a href="#23" class="mim-tip-reference" title="Schmidt, B., Servidei, S., Gabbai, A. A., Silva, A. C., de Sousa Bulle de Oliveira, A., DiMauro, S. <strong>McArdle's disease in two generations: autosomal recessive transmission with manifesting heterozygote.</strong> Neurology 37: 1558-1561, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3476861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3476861</a>] [<a href="https://doi.org/10.1212/wnl.37.9.1558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3476861">Schmidt et al. (1987)</a> and <a href="#20" class="mim-tip-reference" title="Papadimitriou, A., Manta, P., Divari, R., Karabetsos, A., Papadimitriou, E., Bresolin, N. <strong>McArdle's disease: two clinical expressions in the same pedigree.</strong> J. Neurol. 237: 267-270, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2391551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2391551</a>] [<a href="https://doi.org/10.1007/BF00314633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2391551">Papadimitriou et al. (1990)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2391551+8316268+1067063+3476861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bartram, C., Edwards, R. H. T., Clague, J., Beynon, R. J. <strong>McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases.</strong> Hum. Molec. Genet. 2: 1291-1293, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401511</a>] [<a href="https://doi.org/10.1093/hmg/2.8.1291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401511">Bartram et al. (1993)</a> found the R49X mutation in all 16 McArdle disease patients studied; 10 of the 16 were homozygous, and the remainder were heterozygous, with the other allele awaiting identification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401511" 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="#29" class="mim-tip-reference" title="Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W. <strong>Mutation analysis in myophosphorylase deficiency (McArdle's disease).</strong> Ann. Neurol. 43: 326-331, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9506549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9506549</a>] [<a href="https://doi.org/10.1002/ana.410430310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9506549">Vorgerd et al. (1998)</a> performed mutation analysis in 9 patients from 8 unrelated German families with typical myophosphorylase deficiency. They found the R49X mutation in homozygous state in 4 patients as well as in compound heterozygous state in 3 others, suggesting that this is the most common mutation associated with myophosphorylase deficiency in Germans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9506549" 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="Martin, M. A., Rubio, J. C., Garcia, A., Fernandez, M. A., Campos, Y., Krawczak, M., Cooper, D. N., Arenas, J. <strong>Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.</strong> Clin. Genet. 59: 48-51, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11168025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11168025</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590108.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11168025">Martin et al. (2001)</a> performed mutation analysis on DNA from 54 Spanish patients (40 families) with glycogen storage disease V and found the R49X mutation in 70% of patients and 55% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11168025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Martin, M. A., Rubio, J. C., Wevers, R. A., Van Engelen, B. G. M., Steenbergen, G. C. H., Van Diggelen, O. P., De Visser, M., de Die-Smulders, C., Blazquez, A., Andreu, A. L., Arenas, J. <strong>Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle's disease.</strong> Ann. Hum. Genet. 68: 17-22, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14748827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14748827</a>] [<a href="https://doi.org/10.1046/j.1529-8817.2003.00067.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14748827">Martin et al. (2004)</a> demonstrated that the R49X mutation is the most common among Dutch patients with McArdle disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14748827" 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="#1" class="mim-tip-reference" title="Andreu, A. L., Nogales-Gadea, G., Cassandrini, D., Arenas, J., Bruno, C. <strong>McArdle disease: molecular genetic update.</strong> Acta Myol. 26: 53-57, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17915571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17915571</a>]" pmid="17915571">Andreu et al. (2007)</a> stated that the R49X mutation is now referred to as R50X. The highest frequency of R50X is in Great Britain and North America (81% and 63%, respectively), with approximately 50% frequency in other European countries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17915571" 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 MCARDLE DISEASE</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> rs119103251 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103251;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/rs119103251?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=rs119103251" 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=rs119103251" 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=RCV000002389 OR RCV000414632" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002389, RCV000414632" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002389...</a>
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<p>For discussion of the gly205-to-ser (G205S) mutation in the PYGM gene that was found in compound heterozygous state in patients with McArdle disease (GSD5; <a href="/entry/232600">232600</a>) by <a href="#25" class="mim-tip-reference" title="Tsujino, S., Shanske, S., DiMauro, S. <strong>Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease).</strong> New Eng. J. Med. 329: 241-245, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8316268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8316268</a>] [<a href="https://doi.org/10.1056/NEJM199307223290404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8316268">Tsujino et al. (1993)</a>, see <a href="#0001">608455.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8316268" 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="Martin, M. A., Rubio, J. C., Garcia, A., Fernandez, M. A., Campos, Y., Krawczak, M., Cooper, D. N., Arenas, J. <strong>Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.</strong> Clin. Genet. 59: 48-51, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11168025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11168025</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590108.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11168025">Martin et al. (2001)</a> performed mutation analysis on DNA from 54 Spanish patients (40 families) with GSD5 and found the G205S mutation in 14.8% of patients and 9% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11168025" 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 MCARDLE DISEASE</strong>
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PYGM, LYS543THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs119103252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103252;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=rs119103252" 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=rs119103252" 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=RCV000002390" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002390" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002390</a>
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<p>For discussion of the lys543-to-thr (K543T) mutation in the PYGM gene that was found in compound heterozygous state in patients with McArdle disease (GSD5; <a href="/entry/232600">232600</a>) by <a href="#25" class="mim-tip-reference" title="Tsujino, S., Shanske, S., DiMauro, S. <strong>Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease).</strong> New Eng. J. Med. 329: 241-245, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8316268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8316268</a>] [<a href="https://doi.org/10.1056/NEJM199307223290404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8316268">Tsujino et al. (1993)</a>, see <a href="#0001">608455.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8316268" 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 MCARDLE DISEASE</strong>
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PYGM, MET1GLY
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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> rs267606993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606993;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/rs267606993?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=rs267606993" 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=rs267606993" 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=RCV000144425" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144425" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144425</a>
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<p>In a 36-year-old woman who had been diagnosed with scleroderma at age 33 but who was also found to have myophosphorylase deficiency (GSD5; <a href="/entry/232600">232600</a>), <a href="#24" class="mim-tip-reference" title="Tsujino, S., Rubin, L. A., Shanske, S., DiMauro, S. <strong>An A-to-C substitution involving the translation initiation codon in a patient with myophosphorylase deficiency (McArdle's disease).</strong> Hum. Mutat. 4: 73-75, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951262</a>] [<a href="https://doi.org/10.1002/humu.1380040113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951262">Tsujino et al. (1994)</a> identified an A-to-C transversion (ATG to CTG), which abolished the translation initiation codon of the PYGM gene. The patient was a compound heterozygote with a common nonsense mutation, R50X (<a href="#0001">608455.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951262" 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 MCARDLE DISEASE</strong>
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PYGM, GLU654LYS
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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> rs119103253 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103253;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/rs119103253?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=rs119103253" 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=rs119103253" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002392" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002392" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002392</a>
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<p>In a 40-year-old man with McArdle disease (GSD5; <a href="/entry/232600">232600</a>) who complained of myalgia and cramps after intense exercise but had no myoglobinuria, <a href="#26" class="mim-tip-reference" title="Tsujino, S., Shanske, S., Martinuzzi, A., Heiman-Patterson, T., DiMauro, S. <strong>Two novel missense mutations (E654K, L396P) in Caucasian patients with myophosphorylase deficiency (McArdle's disease).</strong> Hum. Mutat. 6: 276-277, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8535454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8535454</a>] [<a href="https://doi.org/10.1002/humu.1380060318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8535454">Tsujino et al. (1995)</a> found compound heterozygosity for mutations in the in the PYGM gene: a G-to-A change, resulting in a glu654-to-lys (E654K) substitution and the common R50X mutation (<a href="#0001">608455.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8535454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 MCARDLE DISEASE</strong>
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PYGM, LEU396PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs119103254 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103254;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=rs119103254" 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=rs119103254" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002394" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002394" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002394</a>
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<p>In a 22-year-old woman with McArdle disease (GSD5; <a href="/entry/232600">232600</a>) who complained of exercise intolerance and cramps and had had 1 episode of myoglobinuria, <a href="#26" class="mim-tip-reference" title="Tsujino, S., Shanske, S., Martinuzzi, A., Heiman-Patterson, T., DiMauro, S. <strong>Two novel missense mutations (E654K, L396P) in Caucasian patients with myophosphorylase deficiency (McArdle's disease).</strong> Hum. Mutat. 6: 276-277, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8535454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8535454</a>] [<a href="https://doi.org/10.1002/humu.1380060318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8535454">Tsujino et al. (1995)</a> identified a T-to-C change in the PYGM gene, resulting in a leu396-to-pro (L396P) substitution. Data from restriction analysis of the patient's PCR-amplified PYGM transcripts suggested that the mutation was in heterozygous state and that the myophosphorylase gene on the second allele was only faintly expressed. The nature of the mutation on the other allele was not found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8535454" 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>.0007 MCARDLE DISEASE</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> rs771427957 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs771427957;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/rs771427957?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=rs771427957" 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=rs771427957" 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=RCV000423322 OR RCV000624349 OR RCV000763265" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000423322, RCV000624349, RCV000763265" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000423322...</a>
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<p><a href="#13" class="mim-tip-reference" title="Iyengar, S., Kalinsky, H., Weiss, S., Korostishevsky, M., Sadeh, M., Zhao, Y., Kidd, K. K., Bonne-Tamir, B. <strong>Homozygosity by descent for a rare mutation in the myophosphorylase gene is associated with variable phenotypes in a Druze family with McArdle disease.</strong> J. Med. Genet. 34: 391-394, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9152836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9152836</a>] [<a href="https://doi.org/10.1136/jmg.34.5.391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9152836">Iyengar et al. (1997)</a> restudied the consanguineous Druze family with McArdle disease (GSD5; <a href="/entry/232600">232600</a>) reported by <a href="#22" class="mim-tip-reference" title="Sarova-Pinhas, I., Sadeh, M. <strong>McArdle disease in a Druze family.</strong> Israel J. Med. Sci. 25: 64-68, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2703328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2703328</a>]" pmid="2703328">Sarova-Pinhas and Sadeh (1989)</a> and found all affected subjects to be homozygous for a G-to-A transition in the first nucleotide of intron 14 of the PYGM gene, a mutation previously reported by <a href="#27" class="mim-tip-reference" title="Tsujino, S., Shanske, S., Nonaka, I., Eto, Y., Mendell, J. R., Fenichel, G. M., DiMauro, S. <strong>Three new mutations in patients with myophosphorylase deficiency (McArdle disease).</strong> Am. J. Hum. Genet. 54: 44-52, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8279469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8279469</a>]" pmid="8279469">Tsujino et al. (1994)</a>. This mutation resulted in activation of an upstream cryptic splice site in exon 14, causing deletion of 67 basepairs from exon 14 and affecting the glucose binding domain of PYGM. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8279469+9152836+2703328" 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 large Finnish kindred, <a href="#3" class="mim-tip-reference" title="Bruno, C., Lofberg, M., Tamburino, L., Jankala, H., Hadjigeorgiou, G. M., Andreu, A. L., Shanske, S., Somer, H., DiMauro, S. <strong>Molecular characterization of McArdle's disease in two large Finnish families.</strong> J. Neurol. Sci. 165: 121-125, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10450796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10450796</a>] [<a href="https://doi.org/10.1016/s0022-510x(99)00091-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10450796">Bruno et al. (1999)</a> described the same mutation. The mutation at the 5-prime splice site of intron 14 was designated as 1844+G-A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10450796" 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 MCARDLE DISEASE</strong>
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PYGM, GLY685ARG
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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> rs144081869 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs144081869;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/rs144081869?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=rs144081869" 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=rs144081869" 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=RCV000002396 OR RCV001091628 OR RCV003319973 OR RCV003407258" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002396, RCV001091628, RCV003319973, RCV003407258" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002396...</a>
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<p>In 2 affected sibs with myophosphorylase deficiency (GSD5; <a href="/entry/232600">232600</a>), <a href="#29" class="mim-tip-reference" title="Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W. <strong>Mutation analysis in myophosphorylase deficiency (McArdle's disease).</strong> Ann. Neurol. 43: 326-331, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9506549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9506549</a>] [<a href="https://doi.org/10.1002/ana.410430310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9506549">Vorgerd et al. (1998)</a> found compound heterozygosity for a gly685-to-arg (G685R) substitution and the nonsense mutation R50X (<a href="#0001">608455.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9506549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 MCARDLE DISEASE</strong>
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PYGM, ARG575TER
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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> rs119103255 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103255;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/rs119103255?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=rs119103255" 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=rs119103255" 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=RCV000002397 OR RCV000578544" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002397, RCV000578544" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002397...</a>
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<p>In a patient with myophosphorylase deficiency (GSD5; <a href="/entry/232600">232600</a>), <a href="#29" class="mim-tip-reference" title="Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W. <strong>Mutation analysis in myophosphorylase deficiency (McArdle's disease).</strong> Ann. Neurol. 43: 326-331, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9506549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9506549</a>] [<a href="https://doi.org/10.1002/ana.410430310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9506549">Vorgerd et al. (1998)</a> found compound heterozygosity for a nonsense mutation, arg575-to-ter (R575X), and a previously described missense mutation, G205S (<a href="#0002">608455.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9506549" 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 MCARDLE DISEASE</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">rs119103256 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103256;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=rs119103256" 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=rs119103256" 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=RCV000002393 OR RCV003441700" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002393, RCV003441700" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002393...</a>
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<p>In a German patient with myophosphorylase deficiency (GSD5; <a href="/entry/232600">232600</a>), <a href="#29" class="mim-tip-reference" title="Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W. <strong>Mutation analysis in myophosphorylase deficiency (McArdle's disease).</strong> Ann. Neurol. 43: 326-331, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9506549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9506549</a>] [<a href="https://doi.org/10.1002/ana.410430310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9506549">Vorgerd et al. (1998)</a> found compound heterozygosity for mutations in the PYGM gene: gln665-to-glu (Q665E) and a single base deletion (A) in lys753 (<a href="#0011">608455.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9506549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<strong>.0011 MCARDLE DISEASE</strong>
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PYGM, 1-BP DEL, A, CODON 753
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786200874 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200874;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=rs786200874" 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=rs786200874" 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=RCV000002398" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002398" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002398</a>
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<p>For discussion of the 1-bp deletion (A) n lys753 of the PYGM gene that was found in compound heterozygous state in a patient with myophosphorylase deficiency (GSD5; <a href="/entry/232600">232600</a>) by <a href="#29" class="mim-tip-reference" title="Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W. <strong>Mutation analysis in myophosphorylase deficiency (McArdle's disease).</strong> Ann. Neurol. 43: 326-331, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9506549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9506549</a>] [<a href="https://doi.org/10.1002/ana.410430310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9506549">Vorgerd et al. (1998)</a>, see <a href="#0010">608455.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9506549" 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 MCARDLE DISEASE</strong>
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PYGM, MET1VAL
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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> rs267606993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606993;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/rs267606993?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=rs267606993" 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=rs267606993" 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=RCV000002399 OR RCV001579810" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002399, RCV001579810" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002399...</a>
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<p>In a Turkish patient with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#29" class="mim-tip-reference" title="Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W. <strong>Mutation analysis in myophosphorylase deficiency (McArdle's disease).</strong> Ann. Neurol. 43: 326-331, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9506549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9506549</a>] [<a href="https://doi.org/10.1002/ana.410430310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9506549">Vorgerd et al. (1998)</a> found homozygosity for an A-to-G transition within the initiation codon of the PYGM gene, resulting in a met1-to-val (M1V) substitution. (See also <a href="#0004">608455.0004</a>.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9506549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0013" class="mim-anchor"></a>
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<strong>.0013 MCARDLE DISEASE</strong>
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PYGM, GLU540TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs119103257 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103257;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=rs119103257" 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=rs119103257" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002400" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002400" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002400</a>
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<p>In a large Finnish kindred with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#3" class="mim-tip-reference" title="Bruno, C., Lofberg, M., Tamburino, L., Jankala, H., Hadjigeorgiou, G. M., Andreu, A. L., Shanske, S., Somer, H., DiMauro, S. <strong>Molecular characterization of McArdle's disease in two large Finnish families.</strong> J. Neurol. Sci. 165: 121-125, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10450796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10450796</a>] [<a href="https://doi.org/10.1016/s0022-510x(99)00091-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10450796">Bruno et al. (1999)</a> identified a mutation in exon 14 of the PYGM gene, resulting in a glu540-to-ter substitution (E540X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10450796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0014" class="mim-anchor"></a>
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<h4>
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<strong>.0014 MCARDLE DISEASE</strong>
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</h4>
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PYGM, 1-BP INS, A/8-BP DEL, CODON 387
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2058376262 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2058376262;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=rs2058376262" 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=rs2058376262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001242446" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001242446" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001242446</a>
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<span class="mim-text-font">
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<p>In 2 sibs with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#17" class="mim-tip-reference" title="Martin, M. A., Rubio, J. C., Garcia, A., Fernandez, M. A., Campos, Y., Krawczak, M., Cooper, D. N., Arenas, J. <strong>Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.</strong> Clin. Genet. 59: 48-51, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11168025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11168025</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590108.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11168025">Martin et al. (2001)</a> identified a micro-insertion/deletion in the PYGM gene in a compound heterozygous state: the previously described 1-bp deletion at codon 753 (<a href="#0011">608455.0011</a>) in exon 18 and a novel insA/8-bp del mutation at codon 387 in exon 10. The novel mutation was predicted to result in premature termination of translation 33 amino acids downstream of the site of mutation, potentially encoding a severely truncated protein of 419 amino acids instead of 841 amino acids. Complete lack of myophosphorylase activity was observed in muscle. <a href="#17" class="mim-tip-reference" title="Martin, M. A., Rubio, J. C., Garcia, A., Fernandez, M. A., Campos, Y., Krawczak, M., Cooper, D. N., Arenas, J. <strong>Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.</strong> Clin. Genet. 59: 48-51, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11168025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11168025</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590108.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11168025">Martin et al. (2001)</a> suggested that the underlying mechanism of mutagenesis may have been slipped mispairing mediated by the formation of a Moebius loop-like secondary intermediate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11168025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0015" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0015 MCARDLE DISEASE</strong>
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</span>
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</h4>
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PYGM, TRP797ARG
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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> rs119103258 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103258;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/rs119103258?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=rs119103258" 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=rs119103258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002402 OR RCV000081312" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002402, RCV000081312" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002402...</a>
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<p><a href="#17" class="mim-tip-reference" title="Martin, M. A., Rubio, J. C., Garcia, A., Fernandez, M. A., Campos, Y., Krawczak, M., Cooper, D. N., Arenas, J. <strong>Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.</strong> Clin. Genet. 59: 48-51, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11168025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11168025</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590108.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11168025">Martin et al. (2001)</a> performed mutation analysis on DNA from 54 Spanish patients (40 families) with glycogen storage disease V (GSD5; <a href="/entry/232600">232600</a>) and found that 16.5% of patients and 13.7% of mutant alleles had the W797R substitution previously described by <a href="#7" class="mim-tip-reference" title="Fernandez, R., Navarro, C., Andreu, A. L., Bruno, C., Shanske, S., Gamez, J., Teijeira, S., Hernandez, I., Teijeiro, A., Fernandez, J. M., Musumeci, O., DiMauro, S. <strong>A novel missense mutation (W797R) in the myophosphorylase gene in Spanish patients with McArdle disease.</strong> Arch. Neurol. 57: 217-219, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10681080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10681080</a>] [<a href="https://doi.org/10.1001/archneur.57.2.217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10681080">Fernandez et al. (2000)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10681080+11168025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0016" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0016 MCARDLE DISEASE</strong>
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</h4>
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PYGM, LYS608LYS
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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> rs119103259 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103259;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/rs119103259?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=rs119103259" 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=rs119103259" 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=RCV000002403 OR RCV002251858" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002403, RCV002251858" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002403...</a>
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<p>In a patient with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#8" class="mim-tip-reference" title="Fernandez-Cadenas, I., Andreu, A. L., Gamez, J., Gonzalo, R., Martin, M. A., Rubio, J. C., Arenas, J. <strong>Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle disease.</strong> Neurology 61: 1432-1434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14638972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14638972</a>] [<a href="https://doi.org/10.1212/wnl.61.10.1432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14638972">Fernandez-Cadenas et al. (2003)</a> identified compound heterozygosity for mutations in the PYGM gene. One of the mutations, 1827G-A, was a silent mutation (lys608 to lys; K608K). cDNA studies showed that the change resulted in a severe mosaic alteration in mRNA splicing with multiple aberrant transcripts, including exon skipping, activation of cryptic splice sites, and exon-intron reorganization. The same mutation was identified in a second patient, supporting the idea that the K608K mutation has a primary pathogenic role. The second mutation was a 1722T-G transversion, resulting in a tyr573-to-ter (Y573X) (<a href="#0017">608455.0017</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14638972" 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>.0017 MCARDLE DISEASE</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">rs119103260 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103260;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=rs119103260" 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=rs119103260" 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=RCV000002404" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002404" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002404</a>
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<p>For discussion of the tyr573-to-ter (Y573X) mutation in the PYGM gene that was found in compound heterozygous state in a patient with McArdle disease (GSD5; <a href="/entry/232600">232600</a>) by <a href="#8" class="mim-tip-reference" title="Fernandez-Cadenas, I., Andreu, A. L., Gamez, J., Gonzalo, R., Martin, M. A., Rubio, J. C., Arenas, J. <strong>Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle disease.</strong> Neurology 61: 1432-1434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14638972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14638972</a>] [<a href="https://doi.org/10.1212/wnl.61.10.1432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14638972">Fernandez-Cadenas et al. (2003)</a>, see <a href="#0016">608455.0016</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14638972" 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>.0018 MCARDLE DISEASE, MILD</strong>
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PYGM, IVS5AS, G-A, -601
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1474863903 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1474863903;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=rs1474863903" 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=rs1474863903" 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=RCV000002405 OR RCV001851580" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002405, RCV001851580" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002405...</a>
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<p>In a 30-year-old Swedish woman with a mild form of McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#28" class="mim-tip-reference" title="Vissing, J., Duno, M., Schwartz, M., Haller, R. G. <strong>Splice mutations preserve myophosphorylase activity that ameliorates the phenotype in McArdle disease.</strong> Brain 132: 1545-1552, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433441</a>] [<a href="https://doi.org/10.1093/brain/awp065" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433441">Vissing et al. (2009)</a> identified compound heterozygosity for 2 mutations in the PYGM gene: R50X (<a href="#0001">608455.0001</a>) and a G-to-A transition in intron 5, resulting in a splice site mutation and production of an abnormally spliced fragment in which 175 bp from intron 5 were spliced between exons 5 and 6. There were trace amounts of the aberrantly spliced product, and biochemical studies showed residual PYGM activity (1.0 to 2.5% of normal), suggesting that the splice site mutation was 'leaky' and allowed some normally spliced product to be generated. Although the patient had muscle cramps, pain, and episodes of rhabdomyolysis and myoglobinuria after exercise, she had a high capacity for sustained exercise. Exercise testing showed a phenotype that was intermediate between controls and individuals with typical McArdle disease. The patient could complete 60 minutes of ischemic exercise before muscle cramping occurred, and peak oxidative capacity was about 2-fold higher compared to patients with typical McArdle disease. The findings indicated that very low levels of PYGM are sufficient to sustain glycogenolysis and muscle oxidative metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19433441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0019" class="mim-anchor"></a>
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<strong>.0019 MCARDLE DISEASE, MILD</strong>
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PYGM, IVS3AS, A-G, -26
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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> rs764313717 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs764313717;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/rs764313717?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=rs764313717" 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=rs764313717" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002406 OR RCV000454242 OR RCV001564860" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002406, RCV000454242, RCV001564860" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002406...</a>
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<span class="mim-text-font">
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<p>In a 39-year-old North American man with a mild form of McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#28" class="mim-tip-reference" title="Vissing, J., Duno, M., Schwartz, M., Haller, R. G. <strong>Splice mutations preserve myophosphorylase activity that ameliorates the phenotype in McArdle disease.</strong> Brain 132: 1545-1552, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433441</a>] [<a href="https://doi.org/10.1093/brain/awp065" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19433441">Vissing et al. (2009)</a> identified compound heterozygosity for 2 mutations in the PYGM gene: an A-to-G transition in intron 3, resulting in a splice site mutation and production of an abnormally spliced protein lacking exon 4, and the G205S mutation (<a href="#0002">608455.0002</a>). There were trace amounts of the aberrantly spliced product, and biochemical studies showed residual PYGM activity (1.0 to 2.5% of normal), suggesting that the splice site mutation was 'leaky' and allowed some normally spliced product to be generated. Although the patient had muscle cramps, pain, and episodes of rhabdomyolysis and myoglobinuria after exercise, he had a high capacity for sustained exercise. Exercise testing showed a phenotype that was intermediate between controls and individuals with typical McArdle disease. The patient could complete 60 minutes of ischemic exercise before muscle cramping occurred, and peak oxidative capacity was about 2-fold higher compared to patients with typical McArdle disease. The findings indicated that very low levels of PYGM are sufficient to sustain glycogenolysis and muscle oxidative metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19433441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0020" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0020 MCARDLE DISEASE</strong>
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PYGM, ASP51GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514631 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514631;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=rs397514631" 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=rs397514631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033140" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033140" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033140</a>
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<p>In a male with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#30" class="mim-tip-reference" title="Wu, Y., Weber, J. L., Vladutiu, G. D., Tarnopolsky, M. A. <strong>Six novel mutations in the myophosphorylase gene in patients with McArdle disease and a family with pseudo-dominant inheritance pattern.</strong> Molec. Genet. Metab. 104: 587-591, 2011. Note: Erratum: Molec. Genet. Metab. 111: 539 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21880526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21880526</a>] [<a href="https://doi.org/10.1016/j.ymgme.2011.08.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21880526">Wu et al. (2011)</a> identified compound heterozygous mutations in the PYGM gene: a 152A-G transition resulting in an asp51-to-gly (D51G) substitution at a highly conserved residue inherited from the asymptomatic mother, and the common R50X (<a href="#0001">608455.0001</a>) mutation inherited from the father. This was an instance of pseudodominance, as the affected father was compound heterozygous for R50X and another truncating mutation in the PYGM gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21880526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0021" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0021 MCARDLE DISEASE</strong>
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</h4>
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PYGM, 3-BP DEL, 158ACT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1325298827 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1325298827;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=rs1325298827" 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=rs1325298827" 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=RCV000033141" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033141" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033141</a>
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<p>In a young woman with McArdle disease (GSD5; <a href="/entry/232600">232600</a>), <a href="#30" class="mim-tip-reference" title="Wu, Y., Weber, J. L., Vladutiu, G. D., Tarnopolsky, M. A. <strong>Six novel mutations in the myophosphorylase gene in patients with McArdle disease and a family with pseudo-dominant inheritance pattern.</strong> Molec. Genet. Metab. 104: 587-591, 2011. Note: Erratum: Molec. Genet. Metab. 111: 539 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21880526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21880526</a>] [<a href="https://doi.org/10.1016/j.ymgme.2011.08.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21880526">Wu et al. (2011)</a> identified a homozygous 3-bp deletion (158_160delACT) in the PYGM gene, resulting in the deletion of the highly conserved tyr53 residue. The patient had onset of exercise intolerance in childhood, and was diagnosed at age 25. She had increased serum creatine kinase and decreased myophosphorylase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21880526" 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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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1701414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1701414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1701414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00205166" target="_blank">Full Text</a>]
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<div class="">
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[<a href="https://doi.org/10.1126/science.6587566" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1034/j.1399-0004.2001.590108.x" target="_blank">Full Text</a>]
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Martin, M. A., Rubio, J. C., Wevers, R. A., Van Engelen, B. G. M., Steenbergen, G. C. H., Van Diggelen, O. P., De Visser, M., de Die-Smulders, C., Blazquez, A., Andreu, A. L., Arenas, J.
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[<a href="https://doi.org/10.1046/j.1529-8817.2003.00067.x" target="_blank">Full Text</a>]
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Nogales-Gadea, G., Rubio, J. C., Fernandez-Cadenas, I., Garcia-Consuegra, I., Lucia, A., Cabello, A., Garcia-Arumi, E., Arenas, J., Andreu, A. L., Martin, M. A.
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[<a href="https://doi.org/10.1002/humu.20649" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00314633" target="_blank">Full Text</a>]
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Quinlan, K. G. R., Seto, J. T., Turner, N., Vandebrouck, A., Floetenmeyer, M., Macarthur, D. G., Raftery, J. M., Lek, M., Yang, N., Parton, R. G., Cooney, G. J., North, K. N.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20089531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20089531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20089531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq010" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3476861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3476861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3476861" 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.37.9.1558" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951262" 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.1380040113" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8316268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8316268</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8316268" 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/10.1056/NEJM199307223290404" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8535454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8535454</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8535454" 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.1380060318" target="_blank">Full Text</a>]
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Vissing, J., Duno, M., Schwartz, M., Haller, R. G.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19433441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19433441</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19433441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awp065" target="_blank">Full Text</a>]
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Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W.
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[<a href="https://doi.org/10.1002/ana.410430310" target="_blank">Full Text</a>]
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Wu, Y., Weber, J. L., Vladutiu, G. D., Tarnopolsky, M. A.
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<strong>Six novel mutations in the myophosphorylase gene in patients with McArdle disease and a family with pseudo-dominant inheritance pattern.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21880526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21880526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21880526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2011.08.012" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/7/2013
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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George E. Tiller - updated : 11/14/2011<br>Cassandra L. Kniffin - updated : 3/18/2010<br>Cassandra L. Kniffin - updated : 6/1/2009<br>Cassandra L. Kniffin - updated : 3/10/2008<br>Cassandra L. Kniffin - updated : 2/7/2008<br>Victor A. McKusick - updated : 4/16/2004
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Creation Date:
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<span class="mim-text-font">
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Cassandra L. Kniffin : 2/9/2004
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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alopez : 10/11/2018
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carol : 12/13/2016<br>joanna : 07/01/2016<br>carol : 4/2/2015<br>mcolton : 3/30/2015<br>carol : 1/29/2015<br>carol : 5/8/2014<br>mcolton : 4/28/2014<br>alopez : 2/18/2013<br>ckniffin : 2/7/2013<br>carol : 11/18/2011<br>terry : 11/14/2011<br>carol : 2/14/2011<br>wwang : 3/22/2010<br>ckniffin : 3/18/2010<br>wwang : 6/9/2009<br>ckniffin : 6/1/2009<br>wwang : 3/12/2008<br>ckniffin : 3/10/2008<br>wwang : 2/21/2008<br>ckniffin : 2/7/2008<br>ckniffin : 2/7/2008<br>alopez : 4/20/2004<br>terry : 4/16/2004<br>carol : 3/9/2004<br>ckniffin : 3/9/2004<br>ckniffin : 3/1/2004
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<span class="mim-font">
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<strong>*</strong> 608455
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<h3>
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GLYCOGEN PHOSPHORYLASE, MUSCLE; PYGM
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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MYOPHOSPHORYLASE
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PYGM</em></strong>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 55912009;
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<strong>ICD10CM:</strong> E74.04;
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<strong>
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<em>
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Cytogenetic location: 11q13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 11:64,746,389-64,760,715 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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Inheritance
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<th>
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Phenotype <br /> mapping key
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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11q13.1
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</td>
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<span class="mim-font">
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McArdle disease
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<span class="mim-font">
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232600
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<span class="mim-text-font">
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<p>The PYGM gene encodes the muscle isoform of glycogen phosphorylase (EC 2.4.1.1), which catalyzes and regulates the breakdown of glycogen to glucose-1-phosphate during glycogenolysis. This metabolic pathway is necessary for the generation of ATP during physical activity (Gautron et al., 1987). </p>
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<h4>
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<strong>Cloning and Expression</strong>
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<span class="mim-text-font">
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<p>Gautron et al. (1987) isolated muscle phosphorylase cDNA clones from a human cDNA library. Northern blot experiments revealed 1 specific mRNA of 3.4 kb found uniquely in tissues expressing muscle phosphorylase. The muscle glycogen phosphorylase protein comprises 842 amino acids (Kubisch et al., 1998). </p>
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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 class="mim-text-font">
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<p>Burke et al. (1987) determined the intron/exon structure of the PYGM gene. Kubisch et al. (1998) provided a revised genomic structure for the PYGM gene, which contains 20 exons. </p>
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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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<span class="mim-text-font">
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<p>Lebo et al. (1984) used an improved method of chromosome sorting to assign the gene for skeletal muscle glycogen phosphorylase to chromosome 11. The method used a double laser system to sort chromosomes into 21 groups. A clone of the carboxy-terminal region of the myophosphorylase gene hybridized to a spot containing chromosomes 10, 11, and 12. Using chromosomes from cell lines with translocations of various ones of these 3 chromosomes, including a 4;11 reciprocal translocation, they assigned the gene to 11p13-qter. This location was confirmed by testing a series of Chinese hamster-human somatic cell hybrid DNAs that contained a single human chromosome 11 with various terminal deletions. Lebo et al. (1990) further sublocalized the PYGM gene to the proximal part of band 11q13 by fluorescence in situ hybridization. </p><p>Glaser et al. (1989) mapped the muscle, liver, and brain phosphorylases (Pygm, Pygl, and Pygb) to mouse chromosomes 19, 12, and 2, respectively, by comparing segregations patterns of RFLPs with those of previously mapped genetic markers in an interspecies backcross between Mus musculus domesticus and Mus spretus. A previously mapped 'muscle-deficient' mutation in the mouse (mdf) was found to be closely linked to the muscle phosphorylase gene. However, since muscle phosphorylase gene structure and expression appeared to be unaltered in homozygous mdf/mdf mice, this mutation was determined not to be a model of McArdle disease (232600), which is caused by mutation in the PYGM gene. </p><p>Courseaux et al. (1996) used a combination of methods to refine maps of the approximately 5-Mb region of 11q13 that includes multiple endocrine neoplasia type 1 (MEN1; 131100). They proposed the following gene order: cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM, ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel. </p>
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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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<span class="mim-text-font">
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<p>Among 94 enzyme-probe combinations, Lebo et al. (1990) identified a single MspI polymorphism in the PYGM gene region. This polymorphism and an insertion/deletion polymorphism more 3-prime to the gene were found to be informative in 75% of patients at risk for myophosphorylase deficiency, or McArdle disease (GSD5; 232600). Lebo et al. (1990) noted that the scarcity of polymorphic sites in the PYGM gene contrasted sharply with the situation with the liver phosphorylase gene (PYGL; 613741), the site of the mutation in glycogen storage disease VI (232700); in the case of PYGL, they found 6 polymorphic sites in 15 enzyme-probe combinations. Iwasaki et al. (1992) described highly informative minisatellite and microsatellite polymorphisms at the PYGM locus. </p><p>In a study of 40 patients with McArdle disease, Tsujino et al. (1993) identified 3 distinct point mutations in the PYGM gene (608455.0001-608455.0003). One of these mutations, arg50-to-ter (R50X; 608455.0001), was present in 75% of patients in heterozygous or homozygous state. </p><p>Andreu et al. (2007) provided an update of the molecular genetics of McArdle disease, noting that over 65 mutations in the PYGM gene had been identified. </p><p>Nogales-Gadea et al. (2008) found that 26 (92%) of 28 Spanish patients with McArdle disease showed nonsense-mediated decay (NMD) of their mutant PYGM mRNA transcript, corresponding mainly to mutations resulting in premature termination codons. R50X was the most common mutation in this cohort. </p><p>Garcia-Consuegra et al. (2009) used skeletal muscle mRNA and cDNA analysis to identify a second defect in the PYGM gene in 4 patients with McArdle disease in whom heterozygous PYGM mutations were initially detected by genomic DNA analysis. They identified a large deletion and splice site mutation in 1 patient each and a synonymous (K215K) substitution in exon 5 in 2 patients. Real-time PCR of muscle from 1 patient with the K215K substitution showed a drastic decrease in mRNA, implicating nonsense-mediated mRNA decay as a mechanism. </p><p>In 5 unrelated patients with McArdle disease, Wu et al. (2011) identified compound heterozygosity for the common R50X mutation and another pathogenic mutation in the PYGM gene (see, e.g., D51G, 608455.0020). A sixth patient was homozygous for a small deletion (608455.0021). All had typical features of the disorder, including exercise intolerance, decreased or absent PYGM activity and immunostaining in muscle samples, and increased serum creatine kinase. Three had rhabdomyolysis and myoglobinuria. Muscle biopsy of 5 patients showed glycogen accumulation. Although the median age at diagnosis was 29.5 years, most recalled having onset of symptoms in childhood or adolescence. </p>
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</span>
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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>Vissing et al. (2009) reported 2 unrelated patients, aged 30 and 39 years, respectively, with a mild form of McArdle disease (232600) caused by compound heterozygosity for PYGM mutation. Each patient carried 1 typical mutation (R50X, 608455.0001; G205S, 608455.0002) and 1 splice site mutation (608455.0018 and 608455.0019). The splice site mutations were found to cause aberrant splicing and production of abnormally spliced proteins that were expressed in small amounts. Biochemical studies showed 1.0 to 2.5% residual PYGM activity, suggesting that the mutations were 'leaky' and allowed some normally spliced products to be generated. Both patients reported muscle cramps, pain, and episodes of rhabdomyolysis and myoglobinuria after exercise. One had 2 to 3 episodes, whereas the other had more than 10 with 1 episode of renal failure. Both also had increased serum creatine kinase, similar to patients with typical disease. However, both patients also had a high capacity for sustained exercise. Exercise testing showed an intermediate phenotype between controls and individuals with typical McArdle disease. The patients could complete 60 minutes of ischemic exercise before muscle cramping occurred, and peak oxidative capacity was about 2-fold higher compared to patients with typical McArdle disease. The findings indicated that very low levels of PYGM are sufficient to sustain glycogenolysis and muscle oxidative metabolism, and provided the first genotype/phenotype correlation at the molecular level. </p>
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<h4>
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Homozygosity for a common stop codon in the ACTN3 gene (R577X; 102574.0001) results in complete deficiency of the fast fiber muscle protein alpha-actinin-3. This ACTN3 genotype is associated with human athletic performance, and alpha-actinin-3-deficient mice (Actn3 knockout mice) have a shift in the properties of fast muscle fibers toward slower fiber properties, with increased activity of multiple enzymes in the aerobic metabolic pathway and slower contractile properties. Alpha-actinins have been shown to interact with a number of muscle proteins, including the key metabolic regulator glycogen phosphorylase (GPh). Quinlan et al. (2010) demonstrated a link between alpha-actinin-3 and glycogen metabolism. Actn3 knockout mice had higher muscle glycogen content and a 50% reduction in the activity of GPh. The reduction in enzyme activity was accompanied by altered posttranslational modification of GPh, suggesting that alpha-actinin-3 may regulate GPh activity by altering its level of phosphorylation. Quinlan et al. (2010) proposed that the changes in glycogen metabolism underlie the downstream metabolic consequences of alpha-actinin-3 deficiency. </p>
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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>21 Selected Examples):</strong>
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</span>
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</h4>
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<p />
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MCARDLE DISEASE</strong>
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PYGM, ARG50TER
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<br />
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SNP: rs116987552,
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gnomAD: rs116987552,
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ClinVar: RCV000002388, RCV000081306, RCV000622729, RCV002251857, RCV003319158
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<span class="mim-text-font">
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<p>In a study of 40 patients with McArdle disease (GSD5; 232600), Tsujino et al. (1993) identified 3 distinct point mutations in the PYGM gene. The most common mutation was a C-to-T change in exon 1, reported as an ARG49TER (R49X) substitution but now designated R50X. Eighteen patients were homozygous for the R49X mutation, while 12 were compound heterozygous for the R49X mutation and another mutation, thus accounting for 75% of all patients. The second mutation was a G-to-A change in exon 5, resulting in a gly205-to-ser (G205S; 608455.0002) substitution, reported as a GLY204SER (G204S) substitution. The third mutation was an A-to-C change in exon 14, resulting in a lys543-to-thr (L543T) substitution, reported as a LYS542THR (L542T) substitution. Six of the 40 patients had different mutations in the 2 alleles (i.e., were compound heterozygotes), and 11 were presumed to be compound heterozygotes for a known mutation and an unknown one. Only 5 patients had none of the 3 mutations. In 1 remarkable family, all 3 mutations were present in various combinations in 5 members of the family in which transmission appeared to be autosomal dominant. Thus, this was pseudodominance due to mating of a compound heterozygote with a person carrying a third mutation. Three children were all compound heterozygotes, but compound heterozygotes of 2 different compositions. The mother was a 204/49 compound; the father was a 542 carrier; 2 children were 542/204 compounds and 1 was a 542/49 compound. Presumed autosomal dominant inheritance was reported by Chui and Munsat (1976), and the occurrence of McArdle disease in 2 generations was attributed to manifestations in some heterozygotes by Schmidt et al. (1987) and Papadimitriou et al. (1990). </p><p>Bartram et al. (1993) found the R49X mutation in all 16 McArdle disease patients studied; 10 of the 16 were homozygous, and the remainder were heterozygous, with the other allele awaiting identification. </p><p>Vorgerd et al. (1998) performed mutation analysis in 9 patients from 8 unrelated German families with typical myophosphorylase deficiency. They found the R49X mutation in homozygous state in 4 patients as well as in compound heterozygous state in 3 others, suggesting that this is the most common mutation associated with myophosphorylase deficiency in Germans. </p><p>Martin et al. (2001) performed mutation analysis on DNA from 54 Spanish patients (40 families) with glycogen storage disease V and found the R49X mutation in 70% of patients and 55% of mutant alleles. </p><p>Martin et al. (2004) demonstrated that the R49X mutation is the most common among Dutch patients with McArdle disease. </p><p>Andreu et al. (2007) stated that the R49X mutation is now referred to as R50X. The highest frequency of R50X is in Great Britain and North America (81% and 63%, respectively), with approximately 50% frequency in other European countries. </p>
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</span>
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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>.0002 MCARDLE DISEASE</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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PYGM, GLY205SER
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<br />
|
|
|
|
SNP: rs119103251,
|
|
|
|
|
|
gnomAD: rs119103251,
|
|
|
|
|
|
ClinVar: RCV000002389, RCV000414632
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gly205-to-ser (G205S) mutation in the PYGM gene that was found in compound heterozygous state in patients with McArdle disease (GSD5; 232600) by Tsujino et al. (1993), see 608455.0001. </p><p>Martin et al. (2001) performed mutation analysis on DNA from 54 Spanish patients (40 families) with GSD5 and found the G205S mutation in 14.8% of patients and 9% of mutant alleles. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, LYS543THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103252,
|
|
|
|
|
|
|
|
ClinVar: RCV000002390
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the lys543-to-thr (K543T) mutation in the PYGM gene that was found in compound heterozygous state in patients with McArdle disease (GSD5; 232600) by Tsujino et al. (1993), see 608455.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, MET1GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606993,
|
|
|
|
|
|
gnomAD: rs267606993,
|
|
|
|
|
|
ClinVar: RCV000144425
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 36-year-old woman who had been diagnosed with scleroderma at age 33 but who was also found to have myophosphorylase deficiency (GSD5; 232600), Tsujino et al. (1994) identified an A-to-C transversion (ATG to CTG), which abolished the translation initiation codon of the PYGM gene. The patient was a compound heterozygote with a common nonsense mutation, R50X (608455.0001). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, GLU654LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103253,
|
|
|
|
|
|
gnomAD: rs119103253,
|
|
|
|
|
|
ClinVar: RCV000002392
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 40-year-old man with McArdle disease (GSD5; 232600) who complained of myalgia and cramps after intense exercise but had no myoglobinuria, Tsujino et al. (1995) found compound heterozygosity for mutations in the in the PYGM gene: a G-to-A change, resulting in a glu654-to-lys (E654K) substitution and the common R50X mutation (608455.0001). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, LEU396PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103254,
|
|
|
|
|
|
|
|
ClinVar: RCV000002394
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 22-year-old woman with McArdle disease (GSD5; 232600) who complained of exercise intolerance and cramps and had had 1 episode of myoglobinuria, Tsujino et al. (1995) identified a T-to-C change in the PYGM gene, resulting in a leu396-to-pro (L396P) substitution. Data from restriction analysis of the patient's PCR-amplified PYGM transcripts suggested that the mutation was in heterozygous state and that the myophosphorylase gene on the second allele was only faintly expressed. The nature of the mutation on the other allele was not found. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, IVS14, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs771427957,
|
|
|
|
|
|
gnomAD: rs771427957,
|
|
|
|
|
|
ClinVar: RCV000423322, RCV000624349, RCV000763265
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Iyengar et al. (1997) restudied the consanguineous Druze family with McArdle disease (GSD5; 232600) reported by Sarova-Pinhas and Sadeh (1989) and found all affected subjects to be homozygous for a G-to-A transition in the first nucleotide of intron 14 of the PYGM gene, a mutation previously reported by Tsujino et al. (1994). This mutation resulted in activation of an upstream cryptic splice site in exon 14, causing deletion of 67 basepairs from exon 14 and affecting the glucose binding domain of PYGM. </p><p>In a large Finnish kindred, Bruno et al. (1999) described the same mutation. The mutation at the 5-prime splice site of intron 14 was designated as 1844+G-A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, GLY685ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs144081869,
|
|
|
|
|
|
gnomAD: rs144081869,
|
|
|
|
|
|
ClinVar: RCV000002396, RCV001091628, RCV003319973, RCV003407258
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected sibs with myophosphorylase deficiency (GSD5; 232600), Vorgerd et al. (1998) found compound heterozygosity for a gly685-to-arg (G685R) substitution and the nonsense mutation R50X (608455.0001). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, ARG575TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103255,
|
|
|
|
|
|
gnomAD: rs119103255,
|
|
|
|
|
|
ClinVar: RCV000002397, RCV000578544
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with myophosphorylase deficiency (GSD5; 232600), Vorgerd et al. (1998) found compound heterozygosity for a nonsense mutation, arg575-to-ter (R575X), and a previously described missense mutation, G205S (608455.0002). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, GLN665GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103256,
|
|
|
|
|
|
|
|
ClinVar: RCV000002393, RCV003441700
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a German patient with myophosphorylase deficiency (GSD5; 232600), Vorgerd et al. (1998) found compound heterozygosity for mutations in the PYGM gene: gln665-to-glu (Q665E) and a single base deletion (A) in lys753 (608455.0011). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, 1-BP DEL, A, CODON 753
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786200874,
|
|
|
|
|
|
|
|
ClinVar: RCV000002398
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion (A) n lys753 of the PYGM gene that was found in compound heterozygous state in a patient with myophosphorylase deficiency (GSD5; 232600) by Vorgerd et al. (1998), see 608455.0010. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, MET1VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606993,
|
|
|
|
|
|
gnomAD: rs267606993,
|
|
|
|
|
|
ClinVar: RCV000002399, RCV001579810
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish patient with McArdle disease (GSD5; 232600), Vorgerd et al. (1998) found homozygosity for an A-to-G transition within the initiation codon of the PYGM gene, resulting in a met1-to-val (M1V) substitution. (See also 608455.0004.) </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, GLU540TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103257,
|
|
|
|
|
|
|
|
ClinVar: RCV000002400
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Finnish kindred with McArdle disease (GSD5; 232600), Bruno et al. (1999) identified a mutation in exon 14 of the PYGM gene, resulting in a glu540-to-ter substitution (E540X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, 1-BP INS, A/8-BP DEL, CODON 387
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2058376262,
|
|
|
|
|
|
|
|
ClinVar: RCV001242446
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with McArdle disease (GSD5; 232600), Martin et al. (2001) identified a micro-insertion/deletion in the PYGM gene in a compound heterozygous state: the previously described 1-bp deletion at codon 753 (608455.0011) in exon 18 and a novel insA/8-bp del mutation at codon 387 in exon 10. The novel mutation was predicted to result in premature termination of translation 33 amino acids downstream of the site of mutation, potentially encoding a severely truncated protein of 419 amino acids instead of 841 amino acids. Complete lack of myophosphorylase activity was observed in muscle. Martin et al. (2001) suggested that the underlying mechanism of mutagenesis may have been slipped mispairing mediated by the formation of a Moebius loop-like secondary intermediate. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, TRP797ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103258,
|
|
|
|
|
|
gnomAD: rs119103258,
|
|
|
|
|
|
ClinVar: RCV000002402, RCV000081312
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Martin et al. (2001) performed mutation analysis on DNA from 54 Spanish patients (40 families) with glycogen storage disease V (GSD5; 232600) and found that 16.5% of patients and 13.7% of mutant alleles had the W797R substitution previously described by Fernandez et al. (2000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PYGM, LYS608LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119103259,
|
|
|
|
|
|
gnomAD: rs119103259,
|
|
|
|
|
|
ClinVar: RCV000002403, RCV002251858
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with McArdle disease (GSD5; 232600), Fernandez-Cadenas et al. (2003) identified compound heterozygosity for mutations in the PYGM gene. One of the mutations, 1827G-A, was a silent mutation (lys608 to lys; K608K). cDNA studies showed that the change resulted in a severe mosaic alteration in mRNA splicing with multiple aberrant transcripts, including exon skipping, activation of cryptic splice sites, and exon-intron reorganization. The same mutation was identified in a second patient, supporting the idea that the K608K mutation has a primary pathogenic role. The second mutation was a 1722T-G transversion, resulting in a tyr573-to-ter (Y573X) (608455.0017) substitution. </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>.0017 MCARDLE DISEASE</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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PYGM, TYR573TER
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<br />
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SNP: rs119103260,
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ClinVar: RCV000002404
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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>For discussion of the tyr573-to-ter (Y573X) mutation in the PYGM gene that was found in compound heterozygous state in a patient with McArdle disease (GSD5; 232600) by Fernandez-Cadenas et al. (2003), see 608455.0016. </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>.0018 MCARDLE DISEASE, MILD</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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PYGM, IVS5AS, G-A, -601
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<br />
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SNP: rs1474863903,
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ClinVar: RCV000002405, RCV001851580
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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 30-year-old Swedish woman with a mild form of McArdle disease (GSD5; 232600), Vissing et al. (2009) identified compound heterozygosity for 2 mutations in the PYGM gene: R50X (608455.0001) and a G-to-A transition in intron 5, resulting in a splice site mutation and production of an abnormally spliced fragment in which 175 bp from intron 5 were spliced between exons 5 and 6. There were trace amounts of the aberrantly spliced product, and biochemical studies showed residual PYGM activity (1.0 to 2.5% of normal), suggesting that the splice site mutation was 'leaky' and allowed some normally spliced product to be generated. Although the patient had muscle cramps, pain, and episodes of rhabdomyolysis and myoglobinuria after exercise, she had a high capacity for sustained exercise. Exercise testing showed a phenotype that was intermediate between controls and individuals with typical McArdle disease. The patient could complete 60 minutes of ischemic exercise before muscle cramping occurred, and peak oxidative capacity was about 2-fold higher compared to patients with typical McArdle disease. The findings indicated that very low levels of PYGM are sufficient to sustain glycogenolysis and muscle oxidative metabolism. </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>.0019 MCARDLE DISEASE, MILD</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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PYGM, IVS3AS, A-G, -26
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<br />
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SNP: rs764313717,
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gnomAD: rs764313717,
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ClinVar: RCV000002406, RCV000454242, RCV001564860
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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 39-year-old North American man with a mild form of McArdle disease (GSD5; 232600), Vissing et al. (2009) identified compound heterozygosity for 2 mutations in the PYGM gene: an A-to-G transition in intron 3, resulting in a splice site mutation and production of an abnormally spliced protein lacking exon 4, and the G205S mutation (608455.0002). There were trace amounts of the aberrantly spliced product, and biochemical studies showed residual PYGM activity (1.0 to 2.5% of normal), suggesting that the splice site mutation was 'leaky' and allowed some normally spliced product to be generated. Although the patient had muscle cramps, pain, and episodes of rhabdomyolysis and myoglobinuria after exercise, he had a high capacity for sustained exercise. Exercise testing showed a phenotype that was intermediate between controls and individuals with typical McArdle disease. The patient could complete 60 minutes of ischemic exercise before muscle cramping occurred, and peak oxidative capacity was about 2-fold higher compared to patients with typical McArdle disease. The findings indicated that very low levels of PYGM are sufficient to sustain glycogenolysis and muscle oxidative metabolism. </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>.0020 MCARDLE DISEASE</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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PYGM, ASP51GLY
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<br />
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SNP: rs397514631,
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ClinVar: RCV000033140
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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 male with McArdle disease (GSD5; 232600), Wu et al. (2011) identified compound heterozygous mutations in the PYGM gene: a 152A-G transition resulting in an asp51-to-gly (D51G) substitution at a highly conserved residue inherited from the asymptomatic mother, and the common R50X (608455.0001) mutation inherited from the father. This was an instance of pseudodominance, as the affected father was compound heterozygous for R50X and another truncating mutation in the PYGM 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">
|
|
<strong>.0021 MCARDLE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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PYGM, 3-BP DEL, 158ACT
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<br />
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SNP: rs1325298827,
|
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|
|
ClinVar: RCV000033141
|
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|
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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 young woman with McArdle disease (GSD5; 232600), Wu et al. (2011) identified a homozygous 3-bp deletion (158_160delACT) in the PYGM gene, resulting in the deletion of the highly conserved tyr53 residue. The patient had onset of exercise intolerance in childhood, and was diagnosed at age 25. She had increased serum creatine kinase and decreased myophosphorylase activity. </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>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
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|
<p class="mim-text-font">
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|
Andreu, A. L., Nogales-Gadea, G., Cassandrini, D., Arenas, J., Bruno, C.
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<strong>McArdle disease: molecular genetic update.</strong>
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Acta Myol. 26: 53-57, 2007.
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[PubMed: 17915571]
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<p class="mim-text-font">
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|
Bartram, C., Edwards, R. H. T., Clague, J., Beynon, R. J.
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<strong>McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases.</strong>
|
|
Hum. Molec. Genet. 2: 1291-1293, 1993.
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[PubMed: 8401511]
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Bruno, C., Lofberg, M., Tamburino, L., Jankala, H., Hadjigeorgiou, G. M., Andreu, A. L., Shanske, S., Somer, H., DiMauro, S.
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<strong>Molecular characterization of McArdle's disease in two large Finnish families.</strong>
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J. Neurol. Sci. 165: 121-125, 1999.
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[PubMed: 10450796]
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<p class="mim-text-font">
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Burke, J., Hwang, P., Anderson, L., Lebo, R., Gorin, F., Fletterick, R.
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<strong>Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase.</strong>
|
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Proteins 2: 177-187, 1987.
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[PubMed: 3447177]
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[Full Text: https://doi.org/10.1002/prot.340020303]
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<p class="mim-text-font">
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Chui, L. A., Munsat, T. L.
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<strong>Dominant inheritance of McArdle syndrome.</strong>
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Arch. Neurol. 33: 636-641, 1976.
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[PubMed: 1067063]
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[Full Text: https://doi.org/10.1001/archneur.1976.00500090042008]
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<p class="mim-text-font">
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Courseaux, A., Grosgeorge, J., Gaudray, P., Pannett, A. A. J., Forbes, S. A., Williamson, C., Bassett, D., Thakker, R. V., Teh, B. T., Farnebo, F., Shepherd, J., Skogseid, B., Larsson, C., Giraud, S., Zhang, C. X., Salandre, J., Calender, A.
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<strong>Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13.</strong>
|
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Genomics 37: 354-365, 1996.
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[PubMed: 8938448]
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<li>
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<p class="mim-text-font">
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Fernandez, R., Navarro, C., Andreu, A. L., Bruno, C., Shanske, S., Gamez, J., Teijeira, S., Hernandez, I., Teijeiro, A., Fernandez, J. M., Musumeci, O., DiMauro, S.
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<strong>A novel missense mutation (W797R) in the myophosphorylase gene in Spanish patients with McArdle disease.</strong>
|
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Arch. Neurol. 57: 217-219, 2000.
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[PubMed: 10681080]
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[Full Text: https://doi.org/10.1001/archneur.57.2.217]
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</p>
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<li>
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<p class="mim-text-font">
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Fernandez-Cadenas, I., Andreu, A. L., Gamez, J., Gonzalo, R., Martin, M. A., Rubio, J. C., Arenas, J.
|
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<strong>Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle disease.</strong>
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Neurology 61: 1432-1434, 2003.
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[PubMed: 14638972]
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[Full Text: https://doi.org/10.1212/wnl.61.10.1432]
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</p>
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<li>
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<p class="mim-text-font">
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Garcia-Consuegra, I., Rubio, J. C., Nogales-Gadea, G., Bautista, J., Jimenez, S., Cabello, A., Lucia, A., Andreu, A. L., Arenas, J., Martin, M. A.
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<strong>Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA.</strong>
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J. Med. Genet. 46: 198-202, 2009.
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[PubMed: 19251976]
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[Full Text: https://doi.org/10.1136/jmg.2008.059469]
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</p>
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<li>
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<p class="mim-text-font">
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Gautron, S., Daegelen, D., Mennecier, F., Dubocq, D., Kahn, A., Dreyfus, J.-C.
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<strong>Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency).</strong>
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J. Clin. Invest. 79: 275-281, 1987.
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[PubMed: 3466902]
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[Full Text: https://doi.org/10.1172/JCI112794]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Glaser, T., Matthews, K. E., Hudson, J. W., Seth, P., Housman, D. E., Crerar, M. M.
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<strong>Localization of the muscle, liver and brain glycogen phosphorylase genes on linkage maps of mouse chromosomes 19, 12 and 2, respectively.</strong>
|
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Genomics 5: 510-521, 1989.
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[PubMed: 2575583]
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[Full Text: https://doi.org/10.1016/0888-7543(89)90017-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Iwasaki, H., Stewart, P. W., Dilley, W. G., Holt, M. S., Steinbrueck, T. D., Wells, S. A., Jr., Donis-Keller, H.
|
|
<strong>A minisatellite and a microsatellite polymorphism within 1.5 kb at the human muscle glycogen phosphorylase (PYGM) locus can be amplified by PCR and have combined informativeness of PIC 0.95.</strong>
|
|
Genomics 13: 7-15, 1992.
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[PubMed: 1349582]
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[Full Text: https://doi.org/10.1016/0888-7543(92)90194-w]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Iyengar, S., Kalinsky, H., Weiss, S., Korostishevsky, M., Sadeh, M., Zhao, Y., Kidd, K. K., Bonne-Tamir, B.
|
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<strong>Homozygosity by descent for a rare mutation in the myophosphorylase gene is associated with variable phenotypes in a Druze family with McArdle disease.</strong>
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J. Med. Genet. 34: 391-394, 1997.
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[PubMed: 9152836]
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[Full Text: https://doi.org/10.1136/jmg.34.5.391]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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|
Kubisch, C., Wicklein, E. M., Jentsch, T. J.
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<strong>Molecular diagnosis of McArdle disease: revised genomic structure of the myophosphorylase gene and identification of a novel mutation.</strong>
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Hum. Mutat. 12: 27-32, 1998.
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[PubMed: 9633816]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)12:1<27::AID-HUMU4>3.0.CO;2-#]
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|
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</p>
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|
</li>
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<li>
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|
<p class="mim-text-font">
|
|
Lebo, R. V., Anderson, L. A., DiMauro, S., Lynch, E., Hwang, P., Fletterick, R.
|
|
<strong>Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence.</strong>
|
|
Hum. Genet. 86: 17-24, 1990.
|
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|
|
|
|
[PubMed: 1701414]
|
|
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|
[Full Text: https://doi.org/10.1007/BF00205166]
|
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|
|
|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Lebo, R. V., Gorin, F., Fletterick, R. J., Kao, F.-T., Cheung, M.-C., Bruce, B. D., Kan, Y. W.
|
|
<strong>High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome to chromosome 11.</strong>
|
|
Science 225: 57-59, 1984.
|
|
|
|
|
|
[PubMed: 6587566]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.6587566]
|
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|
|
</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Martin, M. A., Rubio, J. C., Garcia, A., Fernandez, M. A., Campos, Y., Krawczak, M., Cooper, D. N., Arenas, J.
|
|
<strong>Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.</strong>
|
|
Clin. Genet. 59: 48-51, 2001.
|
|
|
|
|
|
[PubMed: 11168025]
|
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|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2001.590108.x]
|
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Martin, M. A., Rubio, J. C., Wevers, R. A., Van Engelen, B. G. M., Steenbergen, G. C. H., Van Diggelen, O. P., De Visser, M., de Die-Smulders, C., Blazquez, A., Andreu, A. L., Arenas, J.
|
|
<strong>Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle's disease.</strong>
|
|
Ann. Hum. Genet. 68: 17-22, 2004.
|
|
|
|
|
|
[PubMed: 14748827]
|
|
|
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|
|
[Full Text: https://doi.org/10.1046/j.1529-8817.2003.00067.x]
|
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|
</p>
|
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</li>
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Vorgerd, M., Kubisch, C., Burwinkel, B., Reichmann, H., Mortier, W., Tettenborn, B., Pongratz, D., Lindemuth, R., Tegenthoff, M., Malin, J.-P., Kilimann, M. W.
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